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329 results on '"Spanish Network for Research in Infectious Diseases (REIPI)"'

1. Molecular characterization of multidrug resistant Enterobacterales strains isolated from liver and kidney transplant recipients in Spain

Author

Marta Fernández-Martínez, Claudia González-Rico, Mónica Gozalo-Margüello, Francesc Marco, Irene Gracia-Ahufinger, Maitane Aranzamendi, Ana M. Sánchez-Díaz, Teresa Vicente-Rangel, Fernando Chaves, Jorge Calvo Montes, Luis Martínez-Martínez, Maria Carmen Fariñas, and ENTHERE Study Group, the Group for Study of Infection in Transplantation of the Spanish Society of Infectious Diseases and Clinical Microbiology (GESITRA-SEIMC) and the Spanish Network for Research in Infectious Diseases (REIPI)

Subjects
Medicine, Science
Abstract

Abstract The objective of this study was to analyse the mechanisms of resistance to carbapenems and other extended-spectrum-β-lactams and to determine the genetic relatedness of multidrug-resistant Enterobacterales (MDR-E) causing colonization or infection in solid-organ transplantation (SOT) recipients. Prospective cohort study in kidney (n = 142), liver (n = 98) or kidney/pancreas (n = 7) transplant recipients between 2014 and 2018 in seven Spanish hospitals. We included 531 MDR-E isolates from rectal swabs obtained before transplantation and weekly for 4–6 weeks after the procedure and 10 MDR-E from clinical samples related to an infection. Overall, 46.2% Escherichia coli, 35.3% Klebsiella pneumoniae, 6.5% Enterobacter cloacae, 6.3% Citrobacter freundii and 5.7% other species were isolated. The number of patients with MDR-E colonization post-transplantation (176; 71.3%) was 2.5-fold the number of patients colonized pre-transplantation (71; 28.7%). Extended-spectrum β-lactamases (ESBLs) and carbapenemases were detected in 78.0% and 21.1% of MDR-E isolates respectively. In nine of the 247 (3.6%) transplant patients, the microorganism causing an infection was the same strain previously cultured from surveillance rectal swabs. In our study we have observed a low rate of MDR-E infection in colonized patients 4–6 weeks post-transplantation. E. coli producing bla CTX-M-G1 and K. pneumoniae harbouring bla OXA-48 alone or with bla CTX-M-G1 were the most prevalent MDR-E colonization strains in SOT recipients.

Published
2021
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2. Empiric Therapy With Carbapenem-Sparing Regimens for Bloodstream Infections due to Extended-Spectrum β-Lactamase–Producing Enterobacteriaceae : Results From the INCREMENT Cohort

Author

Spanish Network for Research in Infectious Diseases (REIPI)/European Study Group of Bloodstream Infections and Sepsis (ESGBIS)/INCREMENT Group, Palacios-Baena, Zaira Raquel, Gutiérrez-Gutiérrez, Belén, Calbo, Esther, Almirante, Benito, Viale, Pierluigi, Oliver, Antonio, Pintado, Vicente, Gasch, Oriol, Martínez-Martínez, Luis, Pitout, Johann, Akova, Murat, Peña, Carmen, Gil-Bermejo, José Molina, Hernández, Alicia, Venditti, Mario, Prim, Nuria, Bou, German, Tacconelli, Evelina, Tumbarello, Mario, Hamprecht, Axel, Giamarellou, Helen, Almela, Manel, Pérez, Federico, Schwaber, Mitchell J., Bermejo, Joaquín, Lowman, Warren, Hsueh, Po-Ren, Paño-Pardo, José Ramón, Torre-Cisneros, Julián, Souli, Maria, Bonomo, Robert A., Carmeli, Yehuda, Paterson, David L., Pascual, Álvaro, and Rodríguez-Baño, Jesús

Published
2017

3. Influence of Virulence Genotype and Resistance Profile in the Mortality of Pseudomonas aeruginosa Bloodstream Infections

Author

Spanish Network for Research in Infectious Diseases (REIPI), Peña, Carmen, Cabot, Gabriel, Gómez-Zorrilla, Silvia, Zamorano, Laura, Ocampo-Sosa, Alain, Murillas, Javier, Almirante, Benito, Pomar, Virginia, Aguilar, Manuela, Granados, Ana, Calbo, Esther, Rodríguez-Baño, Jesús, Rodríguez-López, Fernando, Tubau, Fe, Martínez-Martínez, Luis, and Oliver, Antonio

Published
2015

4. Prevalence and risk factors for multidrug-resistant organisms colonization in long-term care facilities around the world: a review

Author

Universidad de Sevilla. Departamento de Microbiología, Universidad de Sevilla. Departamento de Medicina, European Development Regional Fund 'A way to achieve Europe' ERDF, Spanish Network for the Research in Infectious Diseases, REIPI RD16/0016/0009, European Development Regional Fund "A way to achieve Europe", European Development Regional Fund "A way to achieve Europe", Operative program Intelligent Growth 2014-2020, Instituto de Salud Carlos III, PI17-02195, Instituto de Salud Carlos III, Subdireccion General de Redes y Centros de Investigacion Cooperativa, Ministerio de Economia, Industria y Competitividad, Spanish Network for Research in Infectious Diseases, REIPI RD16/0016/0001, Instituto de Salud Carlos III, Subdireccion General de Redes y Centros de InvestigacionCooperativa, Ministry of Economy, Industry and Competitiveness, Spanish Network for Research in Infectious Diseases, REIPI RD16/0016/0001; RD16/0016/0009, Instituto de Salud Carlos III, the Spanish Ministry of Economy, Industry, and Competitiveness, PI17-02195, Plan Nacional de I+D+i 2013-2016, Servicio Andaluz de Salud, Junta de Andalucia, Spain, C1-0038-2019, Subprograma Rio Hortega, Instituto de Salud Carlos III, Subdireccion General de Redes y Centros de Investigacion Cooperativa, Ministerio de Ciencia, Innovacion y Universidades, Spain, Rodríguez-Villodres, Ángel, Martín-Gandul, Cecilia, Peñalva, Germán, Guisado-Gil, Ana Belén, Crespo-Rivas, Juan Carlos, Pachón-Ibáñez, María Eugenia, Lepe Jiménez, José Antonio, Cisneros, José Miguel, Universidad de Sevilla. Departamento de Microbiología, Universidad de Sevilla. Departamento de Medicina, European Development Regional Fund 'A way to achieve Europe' ERDF, Spanish Network for the Research in Infectious Diseases, REIPI RD16/0016/0009, European Development Regional Fund "A way to achieve Europe", European Development Regional Fund "A way to achieve Europe", Operative program Intelligent Growth 2014-2020, Instituto de Salud Carlos III, PI17-02195, Instituto de Salud Carlos III, Subdireccion General de Redes y Centros de Investigacion Cooperativa, Ministerio de Economia, Industria y Competitividad, Spanish Network for Research in Infectious Diseases, REIPI RD16/0016/0001, Instituto de Salud Carlos III, Subdireccion General de Redes y Centros de InvestigacionCooperativa, Ministry of Economy, Industry and Competitiveness, Spanish Network for Research in Infectious Diseases, REIPI RD16/0016/0001; RD16/0016/0009, Instituto de Salud Carlos III, the Spanish Ministry of Economy, Industry, and Competitiveness, PI17-02195, Plan Nacional de I+D+i 2013-2016, Servicio Andaluz de Salud, Junta de Andalucia, Spain, C1-0038-2019, Subprograma Rio Hortega, Instituto de Salud Carlos III, Subdireccion General de Redes y Centros de Investigacion Cooperativa, Ministerio de Ciencia, Innovacion y Universidades, Spain, Rodríguez-Villodres, Ángel, Martín-Gandul, Cecilia, Peñalva, Germán, Guisado-Gil, Ana Belén, Crespo-Rivas, Juan Carlos, Pachón-Ibáñez, María Eugenia, Lepe Jiménez, José Antonio, and Cisneros, José Miguel

Abstract

Elderly people confined to chronic care facilities face an increased risk of acquiring infections by multidrug-resistant organisms (MDROs). This review presents the current knowledge of the prevalence and risk factors for colonization by MDROs in long-term care facilities (LTCF), thereby providing a useful reference to establish objectives for implementing successful antimicrobial stewardship programs (ASPs). We searched in PubMed and Scopus for studies examining the prevalence of MDROs and/or risk factors for the acquisition of MDROs in LTCF. One hundred and thirty-four studies published from 1987 to 2020 were included. The prevalence of MDROs in LTCF varies between the different continents, where Asia reported the highest prevalence of extended-spectrum ß-lactamase (ESBL) Enterobacterales (71.6%), carbapenem resistant (CR) Enterobacterales (6.9%) and methicillin-resistant Staphylococcus aureus (MRSA) (25.6%) and North America the highest prevalence to MDR Pseudomonas aeruginosa (5.4%), MDR Acinetobacter baumannii (15.0%), vancomycin-resistant Enterococcus spp. (VRE) (4.0%), and Clostridioides difficile (26.1%). Furthermore, MDRO prevalence has experienced changes over time, with increases in MDR P. aeruginosa and extended spectrum ß-lactamase producing Enterobacterales observed starting in 2015 and decreases of CR Enterobacterales, MDR A. baumannii, VRE, MRSA and C. difficile. Several risk factors have been found, such as male sex, chronic wounds, the use of medical devices, and previous antibiotic use. The last of these aspects represents one of the most important modifiable factors for reducing colonization with MDROs through implementing ASPs in LTCF.

Published
2021

5. Effect of Adequate Single-Drug vs Combination Antimicrobial Therapy on Mortality in Pseudomonas aeruginosa Bloodstream Infections: A Post Hoc Analysis of a Prospective Cohort

Author

Spanish Network for Research in Infectious Diseases (REIPI), Peña, Carmen, Suarez, Cristina, Ocampo-Sosa, Alain, Murillas, Javier, Almirante, Benito, Pomar, Virginia, Aguilar, Manuela, Granados, Ana, Calbo, Esther, Rodríguez-Baño, Jesús, Rodríguez, Fernando, Tubau, Fe, Oliver, Antonio, and Martínez-Martínez, Luis

Published
2013
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7. Multicentre, randomised, open-label, phase IV-III study to evaluate the efficacy of cloxacillin plus fosfomycin versus cloxacillin alone in adult patients with methicillin-susceptible Staphylococcus aureus bacteraemia: study protocol for the SAFO trial

Author

Grillo, Sara, Cuervo Requena, Guillermo, Carratalà, Jordi, Sanjuan, Rafael, Aguado, José María, Morata, Laura, Gómez-Zorrilla Martín, Silvia, López-Contreras, Joaquín, Gasch, Oriol, Gomila Grange, Aina, Iftimie, Simona, Garcia Pardo, Graciano, Calbo, Esther, Boix Palop, Lucía, Oriol, Isabel, Jover-Sáenz, Alfredo, López-Cortés, Luis Eduardo, Euba, Gorane, Aguirregabiria, Malen, Garcia-Pais, Maria Jose, Gioia, Francesca, Paño, Jose Ramón, Pedro-Botet Montoya, Ma Luisa, Benítez, Rosa M., Pérez-Rodríguez, Maria Teresa, Meije, Yolanda, Loeches-Yagüe, Maria Belén, Horna, Gertrudis, Berbel, Dámaris, Domínguez, María Ángeles, Padullés Zamora, Ariadna, Cobo Sacristán, Sara, Hereu, Pilar, Videla Cés, Sebastià, Tebé, Cristian, Pallarès, Natàlia, Miró Meda, José M., Pujol, Miquel, SAFO study group, and Spanish Network for Research in Infectious Diseases (REIPI).

Subjects
Clinical trials, Microbiologia, Malalties infeccioses, Communicable diseases, Microbiology, Assaigs clínics
Abstract

Introduction: Methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia is a frequent condition, with high mortality rates. There is a growing interest in identifying new therapeutic regimens able to reduce therapeutic failure and mortality observed with the standard of care of beta-lactam monotherapy. In vitro and small-scale studies have found synergy between cloxacillin and fosfomycin against S. aureus. Our aim is to test the hypothesis that cloxacillin plus fosfomycin achieves higher treatment success than cloxacillin alone in patients with MSSA bacteraemia. Methods: We will perform a superiority, randomised, open-label, phase IV-III, two-armed parallel group (1:1) clinical trial at 20 Spanish tertiary hospitals. Adults (≥18 years) with isolation of MSSA from at least one blood culture ≤72 hours before inclusion with evidence of infection, will be randomly allocated to receive either cloxacillin 2 g/4-hour intravenous plus fosfomycin 3 g/6-hour intravenous or cloxacillin 2 g/4-hour intravenous alone for 7 days. After the first week, sequential treatment and total duration of antibiotic therapy will be determined according to clinical criteria by the attending physician. Primary endpoints: (1) Treatment success at day 7, a composite endpoint comprising all the following criteria: patient alive, stable or with improved quick-Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA at day 7. (2) Treatment success at test of cure (TOC) visit: patient alive and no isolation of MSSA in blood culture or at another sterile site from day 8 until TOC (12 weeks after randomisation). We assume a rate of treatment success of 74% in the cloxacillin group. Accepting alpha risk of 0.05 and beta risk of 0.2 in a two-sided test, 183 subjects will be required in each of the control and experimental groups to obtain statistically significant difference of 12% (considered clinically significant). Ethics and dissemination: Ethical approval has been obtained from the Ethics Committee of Bellvitge University Hospital (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), and is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders.

Published
2021

8. Clinical characteristics and outcome of bacteraemia caused by Enterobacter cloacae and Klebsiella aerogenes: more similarities than differences

Author

Universidad de Sevilla. Departamento de Microbiología, Universidad de Sevilla. Departamento de Medicina, European Regional Development Fund 'A way to achieve Europe', Operative program Intelligent Growth 2014-2020, Instituto Carlos III , PS09/00916, Ministerio de Ciencia e Innovación, Ministerio de Ciencia, Innovación y Universidades (MICINN). España, Plan Nacional I + D +i 2013-2016, Spanish Network for Research in Infectious Diseases [REIPI] RD16/0016/0007; RD16/0016/0005; RD16/0016/0009; RD16/0016/0008; RD16/0016/0001, Subdirección General de Redes y Centros de Investigación Cooperativa, Álvarez-Marín, Rocío, Lepe Jiménez, José Antonio, Gasch-Blasi, Oriol, Rodríguez Martínez, José Manuel, Calvo-Montes, Jorge, Lara-Contreras, Rosario, Rodríguez-Baño, Jesús, Pascual Hernández, Álvaro, Jiménez-Mejías, Manuel E., Universidad de Sevilla. Departamento de Microbiología, Universidad de Sevilla. Departamento de Medicina, European Regional Development Fund 'A way to achieve Europe', Operative program Intelligent Growth 2014-2020, Instituto Carlos III , PS09/00916, Ministerio de Ciencia e Innovación, Ministerio de Ciencia, Innovación y Universidades (MICINN). España, Plan Nacional I + D +i 2013-2016, Spanish Network for Research in Infectious Diseases [REIPI] RD16/0016/0007; RD16/0016/0005; RD16/0016/0009; RD16/0016/0008; RD16/0016/0001, Subdirección General de Redes y Centros de Investigación Cooperativa, Álvarez-Marín, Rocío, Lepe Jiménez, José Antonio, Gasch-Blasi, Oriol, Rodríguez Martínez, José Manuel, Calvo-Montes, Jorge, Lara-Contreras, Rosario, Rodríguez-Baño, Jesús, Pascual Hernández, Álvaro, and Jiménez-Mejías, Manuel E.

Abstract

Objectives The genus Enterobacter is a common cause of nosocomial infections. Historically, the most frequent Enterobacter species were those of Enterobacter cloacae complex and Enterobacter aerogenes. In 2019, E. aerogenes was re-classified as Klebsiella aerogenes owing to its higher genotypic similarity with the genus Klebsiella. Our objective was to characterise and compare the clinical profiles of bacteraemia caused by E. cloacae and K. aerogenes. Methods This 3-year multicentre, prospective cohort study enrolled consecutive patients with bacteraemia by E. cloacae or K. aerogenes. Baseline characteristics, bacteraemia features (source, severity, treatment), antibiotic susceptibility, resistance mechanisms and mortality were analysed. Results The study included 285 patients with bacteraemia [196 (68.8%) E. cloacae and 89 (31.2%) K. aerogenes]. The groups showed no differences in age, sex, previous use of invasive devices, place of acquisition, sources or severity at onset. The Charlson score was higher among patients with E. cloacae bacteraemia [2 (1–4) vs. 1 (0.5–3); P = 0.018], and previous antibiotic therapy was more common in patients with K. aerogenes bacteraemia (57.3% vs. 41.3%; P = 0.01). Mortality was 19.4% for E. cloacae and 20.2% for K. aerogenes (P = 0.869). Antibiotic susceptibility was similar for both species, and the incidence of multidrug resistance or ESBL production was low (6% and 5.3%, respectively), with no differences between species. Conclusion Bacteraemias caused by E. cloacae and K. aerogenes share similar patient profiles, presentation and prognosis. Patients with E. cloacae bacteraemia had more co-morbidities and those with K. aerogenes bacteraemia had received more antibiotics.

Published
2021

9. A new clinical and immuno-virological score for predicting the risk of late severe infection in solid organ transplant recipients: the CLIV Score

Author

San-Juan R, Fernandez-Ruiz M, Ruiz-Ruigomez M, Lopez-Medrano F, Ruiz-Merlo T, Andres A, Loinaz C, Len O, Azancot M, Montejo M, Rodriguez-Alvarez R, Fortun J, Escudero-Sanchez R, Gimenez E, Lora D, Albert E, Navarro D, Aguado J, and Spanish Network for Research in Infectious Diseases (REIPI RD16/0016)

Abstract

BACKGROUND: We aimed at constructing a composite score based on EBVd and simple clinical and immunological parameters to predict late severe infection (LI) beyond month 6 in SOT recipients.; METHODS: Kidney and liver transplant recipients between May 2014-August 2016 at four participating centers were included. Serum immunoglobulins and complement factors, peripheral blood lymphocyte subpopulations, and whole-blood EBVd were determined at months 1, 3 and 6. Cox regression analyses were performed to generate a weighted score for the prediction of LI.; RESULTS: Overall, 309 SOT recipients were followed-up for a median of 1,000 days from transplant (IQR: 822-1124). LI occurred in 104 patients (33.6%). The CLIV score consisted of the following variables at month 6: high-level EBVd (>1,500 IU/ml) and recurrent infection during the previous months (6 points); recipient age =70 years and chronic graft dysfunction (5 points); CMV mismatch (4 points); and CD8+ T-cell count

Published
2020

10. Detection of low-level fosfomycin-resistant variants by decreasing glucose-6-phosphate concentration in fosfomycin susceptibility determination

Author

Universidad de Sevilla. Departamento de Microbiología, Spanish Network for Research in Infectious Diseases REIPI RD16/0016/0009, Martín-Gutiérrez, Guillermo, Docobo Pérez, Fernando, Rodríguez Martínez, José Manuel, Pascual Hernández, Álvaro, Blázquez, Jesús, Rodríguez Beltrán, Jerónimo, Universidad de Sevilla. Departamento de Microbiología, Spanish Network for Research in Infectious Diseases REIPI RD16/0016/0009, Martín-Gutiérrez, Guillermo, Docobo Pérez, Fernando, Rodríguez Martínez, José Manuel, Pascual Hernández, Álvaro, Blázquez, Jesús, and Rodríguez Beltrán, Jerónimo

Abstract

Mutations that confer low-level fosfomycin resistance (LLFR) but not clinical resistance in Escherichia coli are increasingly reported. LLFR strains can become clinically resistant under urinary tract physiological conditions or may act as gateways for highly resistant subpopulations by the selection of additional LLFR mutations. Nevertheless, most LLFR strains are impossible to detect under routine fosfomycin susceptibility determinations. Here, we have explored the possibility of detecting LLFR variants by reducing glucose-6-phosphate (G6P) concentration in fosfomycin susceptibility testing for E. coli strains. As a proof of concept, fosfomycin minimal inhibitory concentrations (MICs) and disk diffusion susceptibility tests were performed for E. coli strain BW25113 and 10 isogenic derivatives carrying the most prevalent LLFR chromosomal mutations (∆uhpT, ∆glpT, ∆cyaA, and ∆ptsI) and their double combinations. Whereas standard G6P concentrations detected only ∆uhpT single and double variants, assays with reduced G6P detected all LLFR variants. In addition, G6P levels were determined to be ≤5 µg/mL in urine samples from 30 patients with urinary tract infection (UTI) caused by E. coli and 10 healthy volunteers, suggesting that most bacterial cells in uncomplicated UTIs are facing fosfomycin under low G6P concentration. Reducing G6P allows for the detection of LLFR variants, which may suppose a risk for future resistance development, especially in UTIs.

Published
2020

11. Assessing the impact on intestinal microbiome and clinical outcomes of antibiotherapy optimisation strategies in haematopoietic stem cell transplant recipients: study protocol for the prospective multicentre OptimBioma study

Author

Universidad de Sevilla. Departamento de Medicina, European Union (ERDF/ESF, `Investing in your future'), Instituto de Salud Carlos III - European Regional Development Fund/European Social Fund A way to make Europe'/`Investing in your future', Instituto de Salud Carlos III (ISCIII), Instituto de Salud Carlos III through the project - European Regional Development Fund/European Social Fund, Plan Nacional de I+D+ i 2013-2016 and Instituto de Salud Carlos III, Subdireccion General de Evaluacion y Fomento de la Investigacion, Ministerio de Economia, Industria y Competitividad, Spanish Clinical Research and Clinical Trials Platform (SCReN), Subdireccion General de Redes y Centros de Investigacion Cooperativa, Ministerio de Economia, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI) - European Development Regional Fund, Jiménez-Jorge, Silvia, Labrador-Herrera, Gema, Rosso-Fernández, Clara M., Rodríguez-Torres, Nancy, Pachón-Ibáñez, María Eugenia, Smani, Younes, Espigado Tocino, Ildefonso, Universidad de Sevilla. Departamento de Medicina, European Union (ERDF/ESF, `Investing in your future'), Instituto de Salud Carlos III - European Regional Development Fund/European Social Fund A way to make Europe'/`Investing in your future', Instituto de Salud Carlos III (ISCIII), Instituto de Salud Carlos III through the project - European Regional Development Fund/European Social Fund, Plan Nacional de I+D+ i 2013-2016 and Instituto de Salud Carlos III, Subdireccion General de Evaluacion y Fomento de la Investigacion, Ministerio de Economia, Industria y Competitividad, Spanish Clinical Research and Clinical Trials Platform (SCReN), Subdireccion General de Redes y Centros de Investigacion Cooperativa, Ministerio de Economia, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI) - European Development Regional Fund, Jiménez-Jorge, Silvia, Labrador-Herrera, Gema, Rosso-Fernández, Clara M., Rodríguez-Torres, Nancy, Pachón-Ibáñez, María Eugenia, Smani, Younes, and Espigado Tocino, Ildefonso

Abstract

Introduction: Haematopoietic stem cell transplantation (HSCT) is a life-saving treatment for a number of haematological diseases. Graft versus host disease (GVHD) is its main complication and hampers survival. There is strong evidence that intestinal microbiota diversity of the recipient may increase the risk of GVHD worsening survival. Antibiotic regimens used during the early phase of the transplant may influence clinical outcomes by reducing intestinal microbiota diversity. Present guidelines of European Conference on Infections in Leukaemia exhort to optimising antibiotic use in haematological patients including HSCT recipients. The present study aims to investigate if, in HSCT recipients, the optimisation of antibacterial use may preserve intestinal microbiota composition reducing the incidence and severity of acute GVHD and improving relevant clinical outcomes. Methods and analysis: This is a prospective longitudinal observational study of two cohorts of HSCT recipients: (1) the intervention cohort includes patients treated in centres in which a predefined strategy of antibiotherapy optimisation is implemented, with the objective of optimising and reducing antibiotic administration according to clinical criteria and (2) the control cohort includes patients treated in centres in which a classic permissive strategy of antibiotic prophylaxis and treatment is used. Adult patient receiving a first HSCT as a treatment for any haematological condition are included. Clinical variables are prospectively recorded and up to five faecal samples are collected for microbiota characterisation at prestablished peritransplant time points. Patients are followed since the preconditioning phase throughout 1-year post-transplant and four follow-up visits are scheduled. Faecal microbiota composition and diversity will be compared between both cohorts along with acute GVHD incidence and severity, severe infections rate, mortality and overall and disease-free survival. Ethics and dis

Published
2020

12. Author Correction: Biofilm formation by multidrug resistant Enterobacteriaceae strains isolated from solid organ transplant recipients

Author

José Ramos-Vivas, Itziar Chapartegui-González, Marta Fernández-Martínez, Claudia González-Rico, Jesús Fortún, Rosa Escudero, Francesc Marco, Laura Linares, Miguel Montejo, Maitane Aranzamendi, Patricia Muñoz, Maricela Valerio, Jose María Aguado, Elena Resino, Irene Gracia Ahufinger, Aurora Paz Vega, Luis Martínez-Martínez, María Carmen Fariñas, and The ENTHERE Study Group, the Group for Study of Infection in Transplantation of the Spanish Society of Infectious Diseases and Clinical Microbiology (GESITRA-SEIMC) and the Spanish Network for Research in Infectious Diseases (REIPI)

Subjects
Multidisciplinary, biology, business.industry, lcsh:R, Biofilm, lcsh:Medicine, Bacterial Infections, Organ Transplantation, biology.organism_classification, Enterobacteriaceae, Microbiology, Multiple drug resistance, Biofilms, Drug Resistance, Multiple, Bacterial, Humans, Medicine, lcsh:Q, Author Correction, Solid organ transplantation, business, lcsh:Science
Abstract

Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant bacteria (MDR). In this study, the biofilm-forming capability of 209 MDR strains (Escherichia coli n = 106, Klebsiella pneumoniae n = 78, and Enterobacter spp. n = 25) isolated from rectal swabs in the first 48 hours before or after kidney (93 patients), liver (60 patients) or kidney/pancreas transplants (5 patients) were evaluated by using a microplate assay. Thirty-nine strains were isolated before transplant and 170 strains were isolated post-transplant. Overall, 16% of E. coli strains, 73% of K. pneumoniae strains and 4% Enterobacter strains showed moderate or strong biofilm production. Nine strains isolated from infection sites after transplantation were responsible of infections in the first month. Of these, 4 K. pneumoniae, 1 E. coli and 1 Enterobacter spp. strains isolated pre-transplant or post-transplant as colonizers caused infections in the post-transplant period. Our results suggest that in vitro biofilm formation could be an important factor for adhesion to intestine and colonization in MDR K. pneumoniae strains in SOT recipients, but this factor appears to be less important for MDR E. coli and Enterobacter spp.

Published
2020
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13. Multinational case-control study of risk factors for the development of late invasive pulmonary aspergillosis following kidney transplantation

Author

López-Medrano, F, Fernández-Ruiz, M, Silva, J T, Carver, P L, van Delden, C, Merino, E, Pérez-Saez, M J, Montero, M, Coussement, J, de Abreu Mazzolin, M, Cervera, C, Santos, L, Sabé, N, Scemla, A, Cordero, E, Cruzado-Vega, L, Martín-Moreno, P L, Len, Ó, Rudas, E, Ponce de León, A, Arriola, M, Lauzurica, R, David, M D, González-Rico, C, Henríquez-Palop, F, Fortún, J, Nucci, M, Manuel, O, Paño-Pardo, J R, Montejo, M, Vena, A, Sánchez-Sobrino, B, Mazuecos, A, Pascual, J, Horcajada, J P, Lecompte, T, Moreno, A, Carratalà, J, Blanes, M, Hernández, D, Hernández-Méndez, E A, Fariñas, M C, Perelló-Carrascosa, M, Muñoz, P, Andrés, A, Aguado, J M, Spanish Network for Research in Infectious Diseases (REIPI), Group for the Study of Infection in Transplant Recipients (GESITRA) of the Spanish Society of Clinical Microbiology and Infectious Diseases (SEIMC), Study Group for Infections in Compromised Hosts (ESGICH) of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Swiss Transplant Cohort Study (STCS), Van Delden, Christian, Spanish Network for Research in Infectious Diseases (REIPI), Group for the Study of Infection in Transplant Recipients (GESITRA) of the Spanish Society of Clinical Microbiology and Infectious Diseases (SEIMC), Study Group for Infections in Compromised Hosts (ESGICH) of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), Swiss Transplant Cohort Study (STCS), and Universitat de Barcelona

Subjects
0301 basic medicine, Male, Respiratory diseases, Aspergil·losi, Time Factors, Trasplantament renal, 030230 surgery, Global Health, Kidney transplantation, 0302 clinical medicine, skin and connective tissue diseases, ddc:616, Invasive Pulmonary Aspergillosis, case-control study, kidney transplantation, late invasive pulmonary aspergillosis, risk factors, Case-control study, Late invasive pulmonary aspergillosis, Risk factors, Factors de risc en les malalties, Kidney Transplantation/adverse effects, Invasive Pulmonary Aspergillosis/etiology, General Medicine, Middle Aged, Infectious Diseases, Female, Microbiology (medical), medicine.medical_specialty, Tuberculosis, Risk factors in diseases, 030106 microbiology, Pulmonary disease, Ronyons -- Trasplantació, Malalties de l'aparell respiratori, 03 medical and health sciences, Internal medicine, medicine, Aspergillosis, Humans, De novo malignancy, Retrospective Studies, business.industry, Pulmons -- Malalties, Invasive pulmonary aspergillosis, bacterial infections and mycoses, medicine.disease, Kidney Transplantation, respiratory tract diseases, Surgery, Global Health/statistics & numerical data, Transplantation, Pneumonia, Case-Control Studies, business
Abstract

To assess the risk factors for development of late-onset invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT). We performed a multinational case-control study that retrospectively recruited 112 KT recipients diagnosed with IPA between 2000 and 2013. Controls were matched (1:1 ratio) by centre and date of transplantation. Immunosuppression-related events (IREs) included the occurrence of non-ventilator-associated pneumonia, tuberculosis, cytomegalovirus disease, and/or de novo malignancy. We identified 61 cases of late (>180 days after transplantation) IPA from 24 participating centres (accounting for 54.5% (61/112) of all cases included in the overall study). Most diagnoses (54.1% (33/61)) were established within the first 36 post-transplant months, although five cases occurred more than 10 years after transplantation. Overall mortality among cases was 47.5% (29/61). Compared with controls, cases were significantly older (p 0.010) and more likely to have pre-transplant chronic obstructive pulmonary disease (p 0.001) and a diagnosis of bloodstream infection (p 0.016) and IRE (p 180 days after transplantation) IPA from 24 participating centres (accounting for 54.5% (61/112) of all cases included in the overall study). Most diagnoses (54.1% (33/61)) were established within the first 36 post-transplant months, although five cases occurred more than 10 years after transplantation. Overall mortality among cases was 47.5% (29/61). Compared with controls, cases were significantly older (p 0.010) and more likely to have pre-transplant chronic obstructive pulmonary disease (p 0.001) and a diagnosis of bloodstream infection (p 0.016) and IRE (p More than half of IPA cases after KT occur beyond the sixth month, with some of them presenting very late. Late IPA entails a poor prognosis. We identified some risk factors that could help the clinician to delimit the subgroup of KT recipients at the highest risk for late IPA.

Published
2017

14. Molecular characterization of multidrug resistant Enterobacterales strains isolated from liver and kidney transplant recipients in Spain.

Author

Fernández-Martínez, Marta, González-Rico, Claudia, Gozalo-Margüello, Mónica, Marco, Francesc, Gracia-Ahufinger, Irene, Aranzamendi, Maitane, Sánchez-Díaz, Ana M., Vicente-Rangel, Teresa, Chaves, Fernando, Calvo Montes, Jorge, Martínez-Martínez, Luis, Fariñas, Maria Carmen, ENTHERE Study Group the Group for Study of Infection in Transplantation of the Spanish Society of Infectious Diseases and Clinical Microbiology (GESITRA-SEIMC) and the Spanish Network for Research in Infectious Diseases (REIPI), Salas, Carlos, Armiñanzas, Carlos, Arnaiz de las Revillas, Francisco, Casafont-Morencos, Fernando, Cuadrado Lavín, Antonio, Fábrega, Emilio, and Fariñas-Álvarez, Concepción

Subjects
CARBAPENEMS, BETA lactamases, MULTIDRUG resistance in bacteria, LIVER transplantation, KIDNEY transplantation
Abstract

The objective of this study was to analyse the mechanisms of resistance to carbapenems and other extended-spectrum-β-lactams and to determine the genetic relatedness of multidrug-resistant Enterobacterales (MDR-E) causing colonization or infection in solid-organ transplantation (SOT) recipients. Prospective cohort study in kidney (n = 142), liver (n = 98) or kidney/pancreas (n = 7) transplant recipients between 2014 and 2018 in seven Spanish hospitals. We included 531 MDR-E isolates from rectal swabs obtained before transplantation and weekly for 4–6 weeks after the procedure and 10 MDR-E from clinical samples related to an infection. Overall, 46.2% Escherichia coli, 35.3% Klebsiella pneumoniae, 6.5% Enterobacter cloacae, 6.3% Citrobacter freundii and 5.7% other species were isolated. The number of patients with MDR-E colonization post-transplantation (176; 71.3%) was 2.5-fold the number of patients colonized pre-transplantation (71; 28.7%). Extended-spectrum β-lactamases (ESBLs) and carbapenemases were detected in 78.0% and 21.1% of MDR-E isolates respectively. In nine of the 247 (3.6%) transplant patients, the microorganism causing an infection was the same strain previously cultured from surveillance rectal swabs. In our study we have observed a low rate of MDR-E infection in colonized patients 4–6 weeks post-transplantation. E. coli producing blaCTX-M-G1 and K. pneumoniae harbouring blaOXA-48 alone or with blaCTX-M-G1 were the most prevalent MDR-E colonization strains in SOT recipients. [ABSTRACT FROM AUTHOR]

Published
2021
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15. Daptomycin plus fosfomycin versus daptomycin monotherapy in treating MRSA: protocol of a multicentre, randomised, phase III trial

Author

Shaw Perujo, Evelyn, Miró Meda, José M., Puig-Asensio, M., Pigrau, C., Barcenilla, F., Murillas Angoiti, Javier, Garcia-Pardo, G., Espejo, Elena, Padilla, Belén, Garcia-Reyne, A., Pasquau, Juan, Rodríguez Baño, Jesús, López-Contreras, J., Montero, Miguel, Calle, Cristina de la, Pintado, Vicente, Calbo, E., Gasch, Oriol, Montejo, Miguel, Salavert, Miguel, Garcia-Pais, M.J., Carratalà, Jordi, Pujol Rojo, Miquel, Spanish Network for Research in Infectious Diseases (REIPI), Instituto de Salud Carlos III, Madrid, Spain, GEIH (Hospital Infection Study Group), Spanish Network for Research in Infectious Diseases (REIPI RD12/0015), Instituto de Salud Carlos III, Madrid, Spain, GEIH (Hospital Infection Study Group), [Shaw ,E, Carratalà,J, Pujol,M] Hospital Universitari de Bellvitge-IDIBELL, Hospitalet de Llobregat, Barcelona, Spain. [Miró,JM, de la Calle C] Hospital Universitari Clínic-IDIBAPS, Barcelona, Spain. [Puig-Asensio,M, Pigrau,C] Hospital Universitari Vall d'Hebron, Barcelona, Spain. [Barcenilla,F] Hospital Universitari Arnau de Vilanova, Lleida, Spain. [Murillas J] Hospital Universitari Son Espases, Mallorca, Spain. [Garcia-Pardo,G] Hospital Universitari Joan XXIII, Tarragona, Spain. [Espejo,E] Hospital Universitari de Terrassa, Terrassa, Barcelona, Spain. [Padilla,B] Hospital Universitario Gregorio Marañon, Madrid, Spain. [Garcia-Reyne,A] Hospital Universitario 12 de Octubre, Madrid, Spain. [Pasquau,J] Hospital Universitario Virgen de las Nieves, Granada, Spain. [Rodriguez-Baño,J] Hospital Universitario Virgen Macarena, Sevilla, Spain. [López-Contreras,J] Hospital Universitari Santa Creu i Sant Pau, Barcelona, Spain. [Montero,M] Hospital Universitari Parc de Salut Mar, Barcelona, Spain. [Pintado,V] Hospital Universitario Ramón y Cajal, Madrid, Spain. [Calbo,E] Hospital Universitari Mutúa de Terrassa, Barcelona, Spain. [Gasch,O] Corporació Sanitaria Parc Taulí, Sabadell, Barcelona, Spain. [Montejo,M] Hospital Universitario de Cruces, Barakaldo, Spain. [Salavert,M] Hospital Universitari i Politècnic la Fe, Valencia, Spain. [Garcia-Pais,MJ] Hospital Universitario Lucus Augusti, Lugo, Spain., This work is supported by grant funding from the National Institute of Health Research, Instituto de Salud Carlos III (ISCIII), Ministerio de Economía y Competitividad. Gobierno de España (Expediente PI12/01907)., and Universitat de Barcelona

Subjects
Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Recurrence [Medical Subject Headings], Pediatrics, bacteraemia, Insuficiencia del Tratamiento, daptomycin, humanos, España, adolescente, Bacteremia, Antibióticos Antituberculosos, medicine.disease_cause, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment Outcome::Treatment Failure [Medical Subject Headings], combination therapy, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Bacterièmia, Clinical trials, infecciones estafilocócicas, Protocol, polycyclic compounds, Organisms::Bacteria::Endospore-Forming Bacteria::Gram-Positive Endospore-Forming Bacteria::Gram-Positive Endospore-Forming Rods::Staphylococcaceae::Staphylococcus::Staphylococcus aureus::Methicillin-Resistant Staphylococcus aureus [Medical Subject Headings], Geographicals::Geographic Locations::Europe::Spain [Medical Subject Headings], Adulto, resultado del tratamiento, Diseases::Bacterial Infections and Mycoses::Bacterial Infections::Bacteremia [Medical Subject Headings], Staphylococcus aureus Resistente a Meticilina, bacteriemia, General Medicine, adulto, Staphylococcal Infections, Anti-Bacterial Agents, Humanos, Estafilococs daurats, Drug Combinations, Análisis de Intención de Tratar, Infectious Diseases, Treatment Outcome, Antibacterianos, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Epidemiologic Study Characteristics as Topic::Clinical Trials as Topic::Controlled Clinical Trials as Topic::Randomized Controlled Trials as Topic::Intention to Treat Analysis [Medical Subject Headings], Research Design, Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams::Penicillins::Methicillin [Medical Subject Headings], pruebas de sensibilidad microbiana, daptomicina, lipids (amino acids, peptides, and proteins), antibacterianos, medicine.drug, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Anti-Bacterial Agents [Medical Subject Headings], Adult, Methicillin-Resistant Staphylococcus aureus, medicine.medical_specialty, Staphylococcus aureus, Combination therapy, Adolescent, Resultado del Tratamiento, Chemicals and Drugs::Polycyclic Compounds::Macrocyclic Compounds::Peptides, Cyclic::Daptomycin [Medical Subject Headings], Staphylococcus aureus resistente a meticilina, Recurrencia, Microbial Sensitivity Tests, Fosfomycin, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Anti-Bacterial Agents::Antibiotics, Antitubercular [Medical Subject Headings], medicine, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], Humans, Septicèmia, Adverse effect, Resistència als medicaments, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment Outcome [Medical Subject Headings], Intention-to-treat analysis, methicillin-resistant Staphylococcus aureus (MRSA), business.industry, Septicemia, biochemical phenomena, metabolism, and nutrition, medicine.disease, bacterial infections and mycoses, Methicillin-resistant Staphylococcus aureus, Clinical trial, fosfomicina, Drug resistance, combinaciones de fármacos, Daptomicina, Bacteriemia, Daptomycin, business, diseño de la investigación, Assaigs clínics, Meticilina
Abstract

Introduction: Despite the availability of new antibiotics such as daptomycin, methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia continues to be associated with high clinical failure rates. Combination therapy has been proposed as an alternative to improve outcomes but there is a lack of clinical studies. The study aims to demonstrate that combination of daptomycin plus fosfomycin achieves higher clinical success rates in the treatment of MRSA bacteraemia than daptomycin alone. Methods and analysis: A multicentre open-label, randomised phase III study. Adult patients hospitalised with MRSA bacteraemia will be randomly assigned (1:1) to group 1: daptomycin 10 mg/kg/24 h intravenous; or group 2: daptomycin 10 mg/kg/24 h intravenous plus fosfomycin 2 gr/6 g intravenous. The main outcome will be treatment response at week 6 after stopping therapy (test-of-cure (TOC) visit). This is a composite variable with two values: Treatment success: resolution of clinical signs and symptoms (clinical success) and negative blood cultures (microbiological success) at the TOC visit. Treatment failure: if any of the following conditions apply: (1) lack of clinical improvement at 72 h or more after starting therapy; (2) persistent bacteraemia (positive blood cultures on day 7); (3) therapy is discontinued early due to adverse effects or for some other reason based on clinical judgement; (4) relapse of MRSA bacteraemia before the TOC visit; (5) death for any reason before the TOC visit. Assuming a 60% cure rate with daptomycin and a 20% difference in cure rates between the two groups, 103 patients will be needed for each group (alpha:0.05, beta: 0.2). Statistical analysis will be based on intention to treat, as well as per protocol and safety analysis. Ethics and dissemination: The protocol was approved by the Spanish Medicines and Healthcare Products Regulatory Agency (AEMPS). The sponsor commits itself to publishing the data in first quartile peer-review journals within 12 months of the completion of the study., This work is supported by grant funding from the National Institute of Health Research, Instituto de Salud Carlos III (ISCIII), Ministerio de Economia y Competitividad. Gobierno de Espana (Expediente PI12/01907).

Published
2015

16. A New Clinical and Immunovirological Score for Predicting the Risk of Late Severe Infection in Solid Organ Transplant Recipients: The CLIV Score.

Author

San-Juan, Rafael, Fernández-Ruiz, Mario, Ruiz-Ruigómez, María, López-Medrano, Francisco, Ruiz-Merlo, Tamara, Andrés, Amado, Loinaz, Carmelo, Len, Oscar, Azancot, María Antonieta, Montejo, Miguel, Rodriguez-Alvarez, Regino, Fortún, Jesús, Escudero-Sánchez, Rosa, Giménez, Estela, Lora, David, Albert, Eliseo, Navarro, David, Aguado, José María, RD16/0016), REIPI, and Spanish Network for Research in Infectious Diseases (REIPI RD16/0016)

Subjects
BK virus, TRANSPLANTATION of organs, tissues, etc., RECEIVER operating characteristic curves, LIVER transplantation, EPSTEIN-Barr virus, OPPORTUNISTIC infections, RESEARCH, DNA, MULTIVARIATE analysis, RESEARCH methodology, SURGICAL complications, IMMUNOSUPPRESSION, EVALUATION research, MEDICAL cooperation, COMPARATIVE studies, LEUKOCYTE count, T cells, EPSTEIN-Barr virus diseases
Abstract

Background: We aimed at constructing a composite score based on Epstein-Barr virus DNAemia (EBVd) and simple clinical and immunological parameters to predict late severe infection (LI) beyond month 6 in solid organ transplantation (SOT) recipients.Methods: Kidney and liver transplant recipients between May 2014 and August 2016 at 4 participating centers were included. Serum immunoglobulins and complement factors, peripheral blood lymphocyte subpopulations, and whole blood EBVd were determined at months 1, 3, and 6. Cox regression analyses were performed to generate a weighted score for the prediction of LI.Results: Overall, 309 SOT recipients were followed-up for a median of 1000 days from transplant (interquartile range, 822-1124). Late severe infection occurred in 104 patients (33.6%). The CLIV Score consisted of the following variables at month 6: high-level EBVd (>1500 IU/mL) and recurrent infection during the previous months (6 points); recipient age ≥70 years and chronic graft dysfunction (5 points); cytomegalovirus mismatch (4 points); and CD8+ T-cell count <400 cells/μL (2 points). The area under receiver operating characteristics curve was 0.77 (95% confidence interval, 0.71-0.84). The risk of LI at day 1000 was as follows: score 0, 12.6%; score 2-5, 25.5%; score 6-9, 52.7%; score ≥10, 73.5%.Conclusions: While waiting for further external validation, the CLIV Score based on clinical and immune-virological parameters is potentially useful to stratify the risk of LI after SOT. [ABSTRACT FROM AUTHOR]

Published
2020
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17. Risk Factors Associated With Early Invasive Pulmonary Aspergillosis in Kidney Transplant Recipients: Results From a Multinational Matched Case-Control Study

Author

López-Medrano, F, Silva, J T, Fernández-Ruiz, M, Carver, P L, van Delden, C, Merino, E, Pérez-Saez, M J, Montero, M, Coussement, J, de Abreu Mazzolin, M, Cervera, C, Santos, L, Sabé, N, Scemla, A, Cordero, E, Cruzado-Vega, L, Martín-Moreno, P L, Len, Ó, Rudas, E, de León, A Ponce, Arriola, M, Lauzurica, R, David, M, González-Rico, C, Henríquez-Palop, F, Fortún, J, Nucci, M, Manuel, O, Paño-Pardo, J R, Montejo, M, Muñoz, P, Sánchez-Sobrino, B, Mazuecos, A, Pascual, J, Horcajada, J P, Lecompte, T, Lumbreras, C, Moreno, A, Carratalà, J, Blanes, M, Hernández, D, Hernández-Méndez, E A, Fariñas, M C, Perelló-Carrascosa, M, Morales, J M, Andrés, A, Aguado, J M, and Spanish Network for Research in Infectious Diseases (REIPI), the Group for the Study of Infection in Transplant Recipients (GESITRA) of the Spanish Society of Clinical Microbiology and Infectious Diseases (SEIMC), the Study Group for Infections in Compromised Hosts (ESGICH) of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), and the Swiss Transplant Cohort Study (STCS)

Subjects
0301 basic medicine, Graft Rejection, Male, medicine.medical_specialty, infection and infectious agents, infectious disease, 030106 microbiology, Delayed Graft Function, kidney transplantation/nephrology, Disease, 030230 surgery, clinical research/practice, Kidney Function Tests, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Epidemiology, medicine, Immunology and Allergy, Humans, Pharmacology (medical), Kidney transplantation, Invasive Pulmonary Aspergillosis, Transplantation, COPD, business.industry, Graft Survival, Case-control study, Odds ratio, Middle Aged, medicine.disease, Prognosis, Kidney Transplantation, Confidence interval, Transplant Recipients, Surgery, fungal, Case-Control Studies, Kidney Failure, Chronic, epidemiology, Female, business, Follow-Up Studies, Glomerular Filtration Rate
Abstract

Risk factors for invasive pulmonary aspergillosis (IPA) after kidney transplantation have been poorly explored. We performed a multinational case-control study that included 51 kidney transplant (KT) recipients diagnosed with early (first 180 posttransplant days) IPA at 19 institutions between 2000 and 2013. Control recipients were matched (1:1 ratio) by center and date of transplantation. Overall mortality among cases was 60.8%, and 25.0% of living recipients experienced graft loss. Pretransplant diagnosis of chronic pulmonary obstructive disease (COPD; odds ratio [OR]: 9.96; 95% confidence interval [CI]: 1.09-90.58; p = 0.041) and delayed graft function (OR: 3.40; 95% CI: 1.08-10.73; p = 0.037) were identified as independent risk factors for IPA among those variables already available in the immediate peritransplant period. The development of bloodstream infection (OR: 18.76; 95% CI: 1.04-339.37; p = 0.047) and acute graft rejection (OR: 40.73, 95% CI: 3.63-456.98; p = 0.003) within the 3 mo prior to the diagnosis of IPA acted as risk factors during the subsequent period. In conclusion, pretransplant COPD, impaired graft function and the occurrence of serious posttransplant infections may be useful to identify KT recipients at the highest risk of early IPA. Future studies should explore the potential benefit of antimold prophylaxis in this group. A multinational case-control study in kidney transplant recipients finds that pretransplant diagnosis of chronic obstructive pulmonary disease, delayed graft function, bloodstream infection and acute graft rejection identify patients at the highest risk for early invasive pulmonary aspergillosis.

Published
2016
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18. Prognosis of urinary tract infection caused by KPC-producing Klebsiella pneumoniae: The impact of inappropriate empirical treatment.

Author

Rodriguez-Gómez, Jorge, Pérez-Nadales, Elena, Gutiérrez-Gutiérrez, Belen, Machuca, Isabel, Martinez-Martinez, Luis, Rivera, Francisco, Cano, Angela, Castón, Juan Jose, Robles, Juan Carlos, de la Fuente, Carmen, Rodríguez-López, Fernando, Rodriguez-Baño, Jesus, Torre-Cisneros, Julian, la Fuente, Carmen De, and Spanish Network for Research in Infectious Diseases (REIPI), Instituto de Salud Carlos III, Madrid, Spain

Abstract

Introduction: There is scarce information on the prognosis of urinary tract infections (UTI) caused by KPC carbapenemase-producing Klebsiella pneumoniae (KPC-Kp).Objetive: To investigate the association between KPC-Kp aetiology and clinical failure and all cause mortality and to explore the impact of inappropriate empirical treatment.Material and Methods: This is a retrospective observational study of hospitalized patients with UTI due to K. pneumoniae. We explored clinical failure at day 21 and 30-day all-cause mortality using different models of adjusted analysis.Results: We analyzed 142 episodes of UTI; 46 episodes (32.4%) were due to KPC-Kp and 96 episodes (67.6%) were due to non-KPC-Kp strains (62 wild type and 34 EBSL producer). Clinical failure was more frequent in the KPC-Kp group (41.3% vs. 15.6%, p = 0.001). KPC-Kp aetiology and inappropriate empirical therapy were associated in the non-adjusted analysis with clinical failure. When analysed in separate adjusted models, both were found to be associated; inappropriate empirical treatment (OR 2.51; 95% CI, 1.03-6.12; p = 0.04) and KPC-Kp (OR 2.73; 95% CI, 1.03-7.22; p = 0.04) were associated with increased risk of failure. All-cause 30-day mortality was higher in patients with KPC-Kp UTI (39.1% vs. 15.6%, p = 0.002). Bacteraemia was more frequent in patients with KPC-Kp etiology (23.9% vs. 10.4%; p = 0.034). In both cases, the association was not confirmed in the adjusted analysis.Conclusion: KPC-Kp UTI is associated with higher clinical failure and may be due to an increase in inappropriate empirical treatment. [ABSTRACT FROM AUTHOR]

Published
2019
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19. Inhibitor-resistant TEM- And OXA-1-producing Escherichia coli isolates resistant to amoxicillin-clavulanate are more clonal and possess lower virulence gene content than susceptible clinical isolates

Author

Oteo Iglesias, Jesús, González López, Juan José, Ortega Fernández, Adriana, Quintero Zárate, J. Natalia, Bou Arévalo, Germán, Cercenado Mansilla, Emilia, Conejo Gonzalo, María Carmen, Martínez Martínez, Luis, Navarro Risueño, Ferrán, Oliver Palomo, Antonio, Bartolomé Comas, Rosa María, Campos Marqués, José, Spanish Network for Research in Infectious Diseases (REIPI), Universidad de Sevilla. Departamento de Microbiología, Instituto de Salud Carlos III, Red de Investigación Cooperativa en Investigación en Patología Infecciosa (España), Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), and Universidad de Cantabria

Subjects
clone (Java method), musculoskeletal diseases, Virulence Factors, Population, Virulence, Biology, medicine.disease_cause, Amoxicillin-Potassium Clavulanate Combination, beta-Lactamases, Microbiology, Epidemiology and Surveillance, Drug Resistance, Bacterial, medicine, Escherichia coli, Humans, Pharmacology (medical), education, Beta-Lactamase Inhibitors, Escherichia coli Infections, Phylogeny, Pharmacology, Genetics, education.field_of_study, Molecular Epidemiology, Molecular epidemiology, Phylogenetic tree, Anti-Bacterial Agents, Infectious Diseases, Multilocus sequence typing, beta-Lactamase Inhibitors, Multilocus Sequence Typing
Abstract

In a previous prospective multicenter study in Spain, we found that OXA-1 and inhibitor-resistant TEM (IRT) β-lactamases constitute the most common plasmid-borne mechanisms of genuine amoxicillin-clavulanate (AMC) resistance in Escherichia coli . In the present study, we investigated the population structure and virulence traits of clinical AMC-resistant E. coli strains expressing OXA-1 or IRT and compared these traits to those in a control group of clinical AMC-susceptible E. coli isolates. All OXA-1-producing ( n = 67) and IRT-producing ( n = 45) isolates were matched by geographical and temporal origin to the AMC-susceptible control set ( n = 56). We performed multilocus sequence typing and phylogenetic group characterization for each isolate and then studied the isolates for the presence of 49 virulence factors (VFs) by PCR and sequencing. The most prevalent clone detected was distinct for each group: group C isolates of sequence type (ST) 88 (C/ST88) were the most common in OXA-1 producers, B2/ST131 isolates were the most common in IRT producers, and B2/ST73 isolates were the most common in AMC-susceptible isolates. The median numbers of isolates per ST were 3.72 in OXA-1 producers, 2.04 in IRT producers, and 1.69 in AMC-susceptible isolates; the proportions of STs represented by one unique isolate in each group were 19.4%, 31.1%, and 48.2%, respectively. The sum of all VFs detected, calculated as a virulence score, was significantly higher in AMC-susceptible isolates than OXA-1 and IRT producers (means, 12.5 versus 8.3 and 8.2, respectively). Our findings suggest that IRT- and OXA-1-producing E. coli isolates resistant to AMC have a different and less diverse population structure than AMC-susceptible clinical E. coli isolates. The AMC-susceptible population also contains more VFs than AMC-resistant isolates.

Published
2014

20. Kinetic of the CMV‐specific T‐cell immune response and CMV infection in CMV‐seropositive kidney transplant recipients receiving rabbit anti‐thymocyte globulin induction therapy: A pilot study.

Author

the Spanish Network for Research in Infectious Diseases (REIPI), Martín‐Gandul, Cecilia, Pérez‐Romero, Pilar, Mena‐Romo, Damián, Molina‐Ortega, Alejandro, Cordero, Elisa, González‐Roncero, Francisco M., Suñer, Marta, and Bernal, Gabriel

Subjects
*IMMUNE response, *CYTOMEGALOVIRUSES, *KIDNEY transplantation, *T cells, *FLOW cytometry
Abstract

Abstract: Background: Some studies have suggested that rATG treatment may be associated with an increased incidence of CMV infection and delayed CMV immune response. However, the evidences supporting this matter are scarce. This study aims to characterize the kinetic of the CMV‐specific T‐cell immune response before and after rATG induction therapy and the relationship with the development of CMV infection in CMV‐seropositive kidney transplant recipients. Methods: An observational prospective study of CMV‐seropositive kidney transplant patients that received rATG induction therapy was performed. A pretransplant sample was obtained before the surgery to determine the CMV‐specific immunity. CMV viral load (by PCR) and CMV‐specific T‐cell immune response (by flow cytometry) were determined during the follow‐up at 0.5, 1, 2, 3, 6, and 12 months post transplantation. Results: A total of 23 patients were included in the study. CMV prophylaxis was administrated for a media of 90 days after transplantation. At the end of follow‐up, 18 (78.3%) patients had CMV‐specific immunity with a median value of 0.31% CD8+CD69+INF‐γ+ T cells at a median of 16 weeks post transplantation. Five patients never acquired CMV‐specific immunity. No statistically significant association between CMV infection and CMV‐specific T‐cell immune response (P = .086) was observed. However, patients with positive pretransplant CMV‐specific immunity developed earlier immunity and achieved higher levels of CD8+CD69+INF‐γ+ T‐cell post‐transplantation than patients with negative pretransplant immunity. Conclusions: CMV‐specific immune monitoring in addition to CMV‐serology may be useful to stratify patient′s risk of CMV infection before transplantation. [ABSTRACT FROM AUTHOR]

Published
2018
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21. Reporting antimicrobial susceptibilities and resistance phenotypes in Acinetobacter spp: a nationwide proficiency study.

Author

Fernández-Cuenca, Felipe, Tomás, María, Caballero-Moyano, Francisco-Javier, Bou, Germán, Pascual, Ávaro, Pascual, Álvaro, Spanish Group of Nosocomial Infections (GEIH), Group of Mechanisms of Action and Resistance to Antimicrobials (GEMARA), Spanish Society of Clinical Microbiology and Infectious Diseases (SEIMC), and Spanish Network for Research in Infectious Diseases (REIPI)

Subjects
ANTI-infective agents, PHENOTYPES, ACINETOBACTER infections, AMPICILLIN, IMIPENEM, ANTIBIOTICS, DRUG resistance in microorganisms, MICROBIAL sensitivity tests, GRAM-negative aerobic bacteria, PHARMACODYNAMICS
Abstract

Objectives: To evaluate the proficiency of Spanish microbiology laboratories with respect to the antimicrobial susceptibility testing (AST) of Acinetobacter spp.Methods: Eight Acinetobacter spp. with different resistance mechanisms were sent to 48 Spanish centres which were asked to report: (i) the AST system used; (ii) MICs; (iii) breakpoints used (CLSI versus EUCAST); (iv) clinical category; and (v) resistance mechanisms inferred. Minor, major and very major errors (mE, ME and VME, respectively) were determined.Results: The greatest percentages of discrepancies were: (i) by AST method: 18.5% Etest, 14.3% Vitek 2 and Sensititre; (ii) by breakpoints: 20.5% (CLSI) and 10.8% (EUCAST); and (iii) by antimicrobial agent: ampicillin/sulbactam (56.2% CLSI), minocycline (40.7% CLSI), tobramycin (38.7% CLSI, 16.8% EUCAST), imipenem (27.8% CLSI, 30.0% EUCAST) and meropenem (25.4% CLSI, 20.8% EUCAST). Categorical error rates: (i) by AST method ranged from 30.0% (Phoenix) to 100% (Sensititre and disc diffusion) for mE, 0.0% (Etest, Sensititre, disc diffusion) to 40% (Phoenix) for ME, and 0.0% (Sensititre and disc diffusion) to 30% (Phoenix) for VME; (ii) by breakpoints: mE (80.1% CLSI, 58.4% EUCAST), ME (3.5% CLSI, 12.4% EUCAST) and VME (16.4% CLSI, 29.2% EUCAST); and (iii) by antimicrobial agent: mE (100% levofloxacin/CLSI, 100% levofloxacin and meropenem/EUCAST), ME (35.3% colistin/CLSI, 25.0% colistin/EUCAST) and VME (64.7% colistin/CLSI, 86.7% gentamicin/EUCAST).Conclusions: Clinical microbiology laboratories must improve their ability to determine antimicrobial susceptibilities of Acinetobacter spp. isolates. Higher discrepancies using CLSI when compared with EUCAST are mainly due to mE and to a much lesser extent to ME or VME. [ABSTRACT FROM AUTHOR]

Published
2018
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22. Left-sided infective endocarditis in patients with liver cirrhosis.

Author

Ruiz-Morales, J., Ivanova-Georgieva, R., Fernández-Hidalgo, N., García-Cabrera, E., Miró, Jose M., Muñoz, P., Almirante, B., Plata-Ciézar, A., González-Ramallo, V., Gálvez-Acebal, J., Fariñas, M.C., Bravo-Ferrer, J.M., Goenaga-Sánchez, M.A., Hidalgo-Tenorio, C., Goikoetxea-Agirre, J., de Alarcón-González, A., Spanish Collaboration on Endocarditis Group-Grupo de Apoyo al Manejo de la Endocarditis en España (GAMES), and Spanish Network for Research in Infectious Diseases (REIPI)

Subjects
COMPARATIVE studies, CARDIAC surgery, INFECTIVE endocarditis, CIRRHOSIS of the liver, LONGITUDINAL method, RESEARCH methodology, MEDICAL cooperation, PROGNOSIS, RESEARCH, EVALUATION research, DISEASE complications
Abstract

Objective: To evaluate the course of left-sided infective endocarditis (LsIE) in patients with liver cirrhosis (LC) analyzing its influence on mortality and the impact of surgery.Methods: Prospective cohort study, conducted from 1984 to 2013 in 26 Spanish hospitals.Results: A total of 3.136 patients with LsIE were enrolled and 308 had LC: 151 Child-Pugh A, 103 B, 34 C and 20 were excluded because of unknown stage. Mortality was significantly higher in the patients with LsIE and LC (42.5% vs. 28.4%; p < 0.01) and this condition was in general an independent worse factor for outcome (HR 1.51, 95% CI: 1.23-1.85; p < 0.001). However, patients in stage A had similar mortality to patients without cirrhosis (31.8% vs. 28.4% p = NS) and in this stage heart surgery had a protective effect (28% in operated patients vs. 60% in non-operated when it was indicated). Mortality was significantly higher in stages B (52.4%) and C (52.9%) and the prognosis was better for patients in stage B who underwent surgery immediately (mortality 50%) compared to those where surgery was delayed (58%) or not performed (74%). Only one patient in stage C underwent surgery.Conclusions: Patients with liver cirrhosis and infective endocarditis have a poorer prognosis only in stages B and C. Early surgery must be performed in stages A and although in selected patients in stage B when indicated. [ABSTRACT FROM AUTHOR]

Published
2015
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23. Reduced susceptibility to biocides in Acinetobacter baumannii: association with resistance to antimicrobials, epidemiological behaviour, biological cost and effect on the expression of genes encoding porins and efflux pumps.

Author

Fernández-Cuenca, Felipe, Tomás, María, Caballero-Moyano, Francisco-Javier, Bou, Germán, Martínez-Martínez, Luis, Vila, Jordi, Pachón, Jerónimo, Cisneros, José-Miguel, Rodríguez-Baño, Jesús, Pascual, Álvaro, and Spanish Group of Nosocomial Infections (GEIH) from the Spanish Society of Clinical Microbiology and Infectious Diseases (SEIMC) and the Spanish Network for Research in Infectious Diseases (REIPI)

Subjects
BIOCIDES, ACINETOBACTER baumannii, ANTI-infective agents, GENES, PORINS (Proteins), ACINETOBACTER infections, ANTIBIOTICS, COMPARATIVE studies, DISINFECTION & disinfectants, DRUG resistance in microorganisms, ENERGY metabolism, GENE expression, RESEARCH methodology, MEDICAL cooperation, MEMBRANE proteins, MICROBIAL sensitivity tests, RESEARCH, EVALUATION research, GRAM-negative aerobic bacteria, MEMBRANE transport proteins, GENOTYPES, PHARMACODYNAMICS, PHYSIOLOGY
Abstract

Objectives: The objective of this study was to analyse whether there is an association between reduced susceptibility to biocides in Acinetobacter baumannii and (i) antimicrobial resistance (co-resistance), (ii) prevalent (epidemic) clones, (iii) changes in the fitness or (iv) expression of genes related to efflux pumps and porins.Methods: Susceptibility to biocides and antimicrobials was determined in 49 clonally unrelated isolates of A. baumannii. Biological cost, in terms of mean generation time, was determined by spectrophotometry. Quantitative real-time RT-PCR was used to determine the relative expression of genes encoding several efflux pumps and porins.Results: Reduced susceptibility to chlorhexidine digluconate, benzalkonium chloride and Irgasan(®) was associated with resistance to aminoglycosides, tetracycline and ciprofloxacin (P < 0.05). The MICs of carbapenems, aminoglycosides, doxycycline and ciprofloxacin for isolate Ab70 (epidemic clone) exposed to these biocides increased by ≥2 dilutions. Reduced susceptibility to Orsan(®) was more frequent among prevalent clones than non-prevalent clones (P < 0.05). Mean generation times for Ab70 before and after exposure to benzalkonium chloride were 57.8 and 78.1 min, respectively (P = 0.02). Relative expression of abeS and adeB was increased in Ab46 and Ab70 after exposure to chlorhexidine digluconate, but was decreased for ompA and carO after exposure to Irgasan(®).Conclusions: Reduced susceptibility to biocides is associated with co-resistance to carbapenems, aminoglycosides, tetracycline and ciprofloxacin. Reduced susceptibility to Orsan(®) may be a marker of prevalent clones. Acquisition of reduced susceptibility to benzalkonium chloride has a biological cost. Exposure to biocides affects the relative expression of genes related to some efflux pump genes (increased expression) or porins (reduced expression). [ABSTRACT FROM AUTHOR]

Published
2015
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24. Neurological complications of infective endocarditis: risk factors, outcome, and impact of cardiac surgery: a multicenter observational study.

Author

García-Cabrera, Emilio, Fernández-Hidalgo, Nuria, Almirante, Benito, Ivanova-Georgieva, Radka, Noureddine, Mariam, Plata, Antonio, Lomas, Jose M, Gálvez-Acebal, Juan, Hidalgo-Tenorio, Carmen, Ruíz-Morales, Josefa, Martínez-Marcos, Francisco J, Reguera, Jose M, de la Torre-Lima, Javier, González, Arístides de Alarcón, Group for the Study of Cardiovascular Infections of the Andalusian Society of Infectious Diseases (SAEI) and the Spanish Network for Research in Infectious Diseases (REIPI), de Alarcón González, Arístides, Group for the Study of Cardiovascular Infections of the Andalusian Society of Infectious Diseases, and Spanish Network for Research in Infectious Diseases

Published
2013
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25. Timing of oseltamivir administration and outcomes in hospitalized adults with pandemic 2009 influenza A(H1N1) virus infection.

Author

Viasus D, Paño-Pardo JR, Pachón J, Riera M, López-Medrano F, Payeras A, Fariñas MC, Moreno A, Rodríguez-Baño J, Oteo JA, Ortega L, Torre-Cisneros J, Segura F, Carratalà J, Novel Influenza A(H1N1) Study Group of the Spanish Network for Research in Infectious Diseases (REIPI), Viasus, Diego, Paño-Pardo, José Ramón, Pachón, Jerónimo, Riera, Melchor, and López-Medrano, Francisco

Abstract

Background: Data on the clinical effectiveness of oseltamivir in patients with pandemic 2009 influenza A(H1N1) (A[H1N1]) virus infection are scarce. We aimed to determine the effect of timing of oseltamivir administration on outcomes in hospitalized adults with A(H1N1).Methods: Observational analysis of a prospective cohort of adults hospitalized with laboratory-confirmed A(H1N1) was performed at 13 Spanish hospitals. Time from onset of symptoms to oseltamivir administration was the independent variable. Outcomes were duration of fever, hospital length of stay (LOS), need for mechanical ventilation, and mortality during hospitalization. Multivariate logistic regression was used to describe the association between the independent variable and the outcomes.Results: Five hundred thirty-eight hospitalized patients with A(H1N1) were studied. The median time from onset of symptoms to oseltamivir administration was 3 days (interquartile range [IQR], 2-5 days). With regard to outcomes, the median duration of fever was 2 days (IQR, 1-3 days), the median LOS was 5 days (IQR, 3-8 days), 49 patients (9.1%) underwent mechanical ventilation, and 11 patients (2%) died during hospitalization. In univariate analysis, prolonged duration of fever (above the median), prolonged LOS (above the median), need for mechanical ventilation, and mortality all increased with time to oseltamivir administration (χ(2) test for trend P = .001, P ≤ .001, P = .008, and P = .001, respectively). After adjustment for confounding factors, time from onset of symptoms to oseltamivir administration (+ 1-day increase) was associated with a prolonged duration of fever (OR, 1.10; 95% CI, 1.02-1.19), prolonged LOS (OR, 1.07; 95% CI, 1.00-1.15), and higher mortality (OR, 1.20; 95% CI, 1.06-1.35).Conclusions: Timely oseltamivir administration has a beneficial effect on outcomes in hospitalized adults with A(H1N1), even in those who are admitted beyond 48 h after onset of symptoms. [ABSTRACT FROM AUTHOR]

Published
2011
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26. Pneumonia complicating pandemic (H1N1) 2009: risk factors, clinical features, and outcomes.

Author

Viasus D, Paño-Pardo JR, Pachón J, Riera M, López-Medrano F, Payeras A, Fariñas MC, Moreno A, Rodríguez-Baño J, Oteo JA, Martínez-Montauti J, Torre-Cisneros J, Segura F, Gudiol F, Carratalà J, Novel Influenza A(H1N1) Study Group of the Spanish Network for Research in Infectious Diseases (REIPI), Viasus, Diego, Paño-Pardo, José Ramón, Pachón, Jerónimo, and Riera, Melchor

Published
2011
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27. Author Correction: Biofilm formation by multidrug resistant Enterobacteriaceae strains isolated from solid organ transplant recipients.

Author

Ramos-Vivas, José, Chapartegui-González, Itziar, Fernández-Martínez, Marta, González-Rico, Claudia, Fortún, Jesús, Escudero, Rosa, Marco, Francesc, Linares, Laura, Montejo, Miguel, Aranzamendi, Maitane, Muñoz, Patricia, Valerio, Maricela, Aguado, Jose María, Resino, Elena, Ahufinger, Irene Gracia, Vega, Aurora Paz, Martínez-Martínez, Luis, Fariñas, María Carmen, The ENTHERE Study Group, the Group for Study of Infection in Transplantation of the Spanish Society of Infectious Diseases and Clinical Microbiology (GESITRA-SEIMC) and the Spanish Network for Research in Infectious Diseases (REIPI), and Millán, Juan Carlos Ruiz San

Subjects
BIOFILMS, ENTEROBACTERIACEAE, MULTIDRUG resistance
Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

Published
2020
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28. In Vitro Antibacterial Activity of Silver Nanoparticles Conjugated with Amikacin and Combined with Hyperthermia against Drug-Resistant and Biofilm-Producing Strains

Author

Marta Palau, Estela Muñoz, Muriel F. Gusta, Nieves Larrosa, Xavier Gomis, Joan Gilabert, Benito Almirante, Victor Puntes, Robert Texidó, Joan Gavaldà, Institut Català de la Salut, [Palau M, Almirante B, Gavaldà J] Laboratori de Resistència Microbiana, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Spanish Network for Research in Infectious Diseases (REIPI RD19/0016), Instituto de Salud Carlos III, Madrid, Spain. CIBERINFEC, ISCIII-CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain. [Muñoz E] Laboratori de Resistència Microbiana, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Freixanet Gusta M] Institut Català de Nanociència i Nanotecnologia (ICN2), CSIC, The Barcelona Institute of Science and Technology (BIST), Campus UAB, Bellaterra, Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. CIBER en Bioingeniería, Biomateriales y Nanomedicina, CIBER-BBN, Madrid, Spain. [Larrosa N] Spanish Network for Research in Infectious Diseases (REIPI RD19/0016), Instituto de Salud Carlos III, Madrid, Spain. CIBERINFEC, ISCIII-CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain. Servei de Microbiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Gomis X] Laboratori de Resistència Microbiana, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. CIBERINFEC, ISCIII-CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain. [Gilabert J] Tractivus SL, Barcelona, Spain i Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain. [Puntes V] Institut Català de Nanociència i Nanotecnologia (ICN2), CSIC, The Barcelona Institute of Science and Technology (BIST), Campus UAB, Bellaterra, Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. CIBER en Bioingeniería, Biomateriales y Nanomedicina, CIBER-BBN, Madrid, Spain. Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Microbiology (medical), General Immunology and Microbiology, Ecology, Nanopartícules, Physiology, Technology, Industry, and Agriculture::Manufactured Materials::Nanostructures::Nanoparticles::Metal Nanoparticles [TECHNOLOGY, INDUSTRY, AND AGRICULTURE], terapéutica::hipertermia inducida [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Cell Biology, acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinfecciosos::antibacterianos [COMPUESTOS QUÍMICOS Y DROGAS], tecnología, industria y agricultura::productos manufacturados::nanoestructuras::nanopartículas::nanopartículas metálicas [TECNOLOGÍA, INDUSTRIA Y AGRICULTURA], Infectious Diseases, Medicaments antiinfecciosos, Genetics, Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Anti-Bacterial Agents [CHEMICALS AND DRUGS], Therapeutics::Hyperthermia, Induced [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Calor - Efectes fisiològics
Abstract

Antibacterial activity; Biofilms; Silver nanoparticles Actividad antibacteriana; Biopelículas; Nanopartículas de plata Activitat antibacteriana; Biopel·lícules; Nanopartícules de plata In view of the current increase and spread of antimicrobial resistance (AMR), there is an urgent need to find new strategies to combat it. This study had two aims. First, we synthesized highly monodispersed silver nanoparticles (AgNPs) of approximately 17 nm, and we functionalized them with mercaptopoly(ethylene glycol) carboxylic acid (mPEG-COOH) and amikacin (AK). Second, we evaluated the antibacterial activity of this treatment (AgNPs_mPEG_AK) alone and in combination with hyperthermia against planktonic and biofilm-growing strains. AgNPs, AgNPs_mPEG, and AgNPs_mPEG_AK were characterized using a suite of spectroscopy and microscopy methods. Susceptibility to these treatments and AK was determined after 24 h and over time against 12 clinical multidrug-resistant (MDR)/extensively drug-resistant (XDR) isolates of Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The efficacy of the treatments alone and in combination with hyperthermia (1, 2, and 3 pulses at 41°C to 42°C for 15 min) was tested against the same planktonic strains using quantitative culture and against one P. aeruginosa strain growing on silicone disks using confocal laser scanning microscopy. The susceptibility studies showed that AgNPs_mPEG_AK was 10-fold more effective than AK alone, and bactericidal efficacy after 4, 8, 24, or 48 h was observed against 100% of the tested strains. The combination of AgNPs_mPEG_AK and hyperthermia eradicated 75% of the planktonic strains and exhibited significant reductions in biofilm formation by P. aeruginosa in comparison with the other treatments tested, except for AgNPs_mPEG_AK without hyperthermia. In conclusion, the combination of AgNPs_mPEG_AK and hyperthermia may be a promising therapy against MDR/XDR and biofilm-producing strains. IMPORTANCE Antimicrobial resistance (AMR) is one of the greatest public health challenges, accounting for 1.27 million deaths worldwide in 2019. Biofilms, a complex microbial community, directly contribute to increased AMR. Therefore, new strategies are urgently required to combat infections caused by AMR and biofilm-producing strains. Silver nanoparticles (AgNPs) exhibit antimicrobial activity and can be functionalized with antibiotics. Although AgNPs are very promising, their effectiveness in complex biological environments still falls below the concentrations at which AgNPs are stable in terms of aggregation. Thus, improving the antibacterial effectiveness of AgNPs by functionalizing them with antibiotics may be a significant change to consolidate AgNPs as an alternative to antibiotics. It has been reported that hyperthermia has a large effect on the growth of planktonic and biofilm-producing strains. Therefore, we propose a new strategy based on AgNPs functionalized with amikacin and combined with hyperthermia (41°C to 42°C) to treat AMR and biofilm-related infections. This study was supported by research grants from the Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III (FIS 01162); la Marató TV3 (472/U/2018); the CaixaImpulse Program (Fundació LaCaixa); and the Spanish Network for Research in Infectious Diseases (REIPI RD19/0016).

Published
2023

29. Autoantibodies against type I IFNs in patients with critical influenza pneumonia

Author

Zhang, Qian, Pizzorno, Andrés, Miorin, Lisa, Bastard, Paul, Gervais, Adrian, Le Voyer, Tom, Bizien, Lucy, Manry, Jeremy, Rosain, Jérémie, Philippot, Quentin, Goavec, Kelian, Wroblewski, Isabelle, Husebye, Eystein, Fellay, Jacques, Pothier, Pierre, Morand, Patrice, Navarrete, Nicolás, Franco, José Luis, Uddin, Mohammed J., Carratalà, Jordi, Merino Díaz, Laura, Palomo, Virginia, Seppänen, Mikko R.J., Särekannu, Karita, Aiuti, Alessandro, Retamar Gentil, Pilar, Debette, Stéphanie, Belot, Alexandre, Abel, Laurent, Soler Palacín, Pere, Abad Arranz, Maria, Aguilar Guisado, Manuela, Meyts, Isabelle, Casanova, Jean-Laurent, Gonzalez Granado, Luis L., Butte, Manish J., Itan, Yuval, Escoresca Ortega, Ana, Morio, Tomohiro, Padey, Blandine, Niubó, Jordi, Gallardo Ríos, Rafaela, Lau, Yu-lung, Triantafyllia, Vasiliki, Briones, Marisa, Saker, Kahina, Richard, Pascale, Drolet, Beth A., Espinosa Padilla, Sara, Wauters, Joost, Peigue Lafeuille, Helene, Valiente, Adoración, El Baghdadi, Jamila, Tiberghien, Pierre, Balsera-manzanero, María, Zins, Marie, Hammarström, Lennart, Andreakos, Evangelos, Notarangelo, Luigi D., Prando, Carolina, Condino-neto, Antonio, Dominguez Pinilla, Nerea, Aydillo, Teresa, Okamoto, Keisuke, Soumaré, Aïcha, Karamitros, Timokratis, Medina, Rafael A., Kisand, Kai, Ramírez Duque, Nieves, Feys, Simon, Romero Oraa, Laura, Kuo, Chen-yen, Lei, Wei-te, Quintana Murci, Lluis, Milner, Joshua D., Ku, Cheng-lung, Van De Beek, Diederik, Hsieh, Elena W.Y., Tal, Galit, Fournet, Thomas, Cerba Healthcare Group, Patural, Hugues, Novelli, Giuseppe, Lyon Antigrippe Working Group, Arias, Andrés A., Rovina, Nikoletta, Rodríguez-gallego, Carlos, Puel, Anne, Jouanguy, Emmanuelle, Vinh, Donald C., Henny, Joseph, Mogensen, Trine H., Cobat, Aurélie, Casari, Giorgio, Ramaswamy, Sathishkumar, Abelenda Alonso, Gabriela, Morel, Pascal, Trouillet Assant, Sophie, Tzourio, Christophe, Gallian, Pierre, Reipi Inf Working Group, García Sastre, Adolfo, Constantinescu, Stefan N., Hamzeh Cognasse, Hind, Haerynck, Filomeen, Flores, Carlos, Bousfiha, Ahmed A., García Salum, Tamara, Shahrooei, Mohammed, Slaby, Ondrej, Fragkou, Paraskevi C., Argaud, Laurent, Shcherbina, Anna, Al-muhsen, Saleh, Biggs, Catherine M., Bogunovic, Dusan, Planas, Anna M., Heath, James R., Von Bernuth, Horst, Dufouil, Carole, Bolze, Alexandre, Boeuf, Benoit, Rodríguez Gallego, Carlos, Christodoulou, John, Bondarenko, Anastasiia, Martin, Fernando, Koltsida, Ourania, Sediva, Anna, Ruiz Hernandez, José Juan, Bonneaudeau, Brigitte, Cannet, Dorothée, Etablissement Français Du Sang Study Group, Froidure, Antoine, Laurent, Emilie, Galani, Ioanna Evdokia, Gregersen, Peter K., Lemonnier, Sylvie, Spaan, András N., Darmon, Michael, Grimbacher, Bodo, Del Mar Muñoz Garcia, Maria, Zawadzki, Pawel, Henrickson, Sarah E., O'farrelly, Cliona, Rosa Calatrava, Manuel, Lachaize, Morgane, Okada, Satoshi, Vanker, Martti, Bryceson, Yenan, Ling, Yun, Cooper, Megan A., Lucas, Carrie L., Maniatis, Tom, Romero Vázquez, Gloria María, Mansouri, Davood, Castagnoli, Riccardo, Maródi, László, Mironska, Kristina, Rapti, Vasiliki, Baris Feldman, Hagit, Pozzetto, Bruno, Renia, Laurent, Tancevski, Ivan, Imai, Kohsuke, Ozcelik, Tayfun, Pan-hammarström, Qiang, Al-mulla, Fahd, Pape, Jean W., Etzioni, Amos, Souweine, Bertrand, Perez De Diego, Rebeca, Sánchez Cordero, Maria Jose, Solé Violán, Jordi, Perlin, David S., Queromes, Gregory, Anderson, Mark S., Resnick, Igor, Pesole, Graziano, Su, Helen C., Vanderbeke, Lore, Hagin, David, Jeanne, Michel, Desai, Murkesh, Ferres, Marcela, Sánchez Céspedes, Javier, Perroquin, Magali, Ng, Lisa F.P., Abou Tayoun, Ahmad, Le Corre, Nicole, Snow, Andrew L., Temel, Şehime Gülsün, Tsiodras, Sotirios, Coeuret Pellicer, Mireille, Javouhey, Etienne, Turvey, Stuart E., Covid Human Genetic Effort, Rombauts, Alexander, Zatz, Mayana, Uddin, K.m. Furkan, Fievet, Nathalie, Jarvis, Erich D., Rodríguez De Castro, Felipe, Ferreres, José, Flaig, Amandine, Pujol, Aurora, Cognasse, Fabrice, Sancho Shimizu, Vanessa, Nadif, Rachel, Hanna, Suhair, Constances Cohort, Goldberg, Marcel, Brodin, Petter, Le Got, Stéphane, Ozguler, Anna, Quenot, Jean Pierre, Novelli, Antonio, Cordero, Elisa, Colomb, Benoit, Cupic, Anastasija, Mehlal Sedkaoui, Souad, Sallette, Jérôme, Hernu, Romain, Bustamante, Carlos D., Lina, Bruno, Halwani, Rabih, Casalegno, Jean Sebastien, Schwebel, Carole, Salamanca Rivera, Celia, 3C-Dijon Study, Tangye, Stuart G., Dalgard, Clifton L., Howard Hughes Medical Institute, Rockefeller University, St. Giles Foundation, National Institutes of Health (US), National Center for Advancing Translational Sciences (US), Fisher Center for Alzheimer's Research Foundation, Meyer Foundation, JPB Foundation, Agence Nationale de la Recherche (France), European Commission, Square Foundation, Ministre de l'Enseignement Supérieur, de la Recherche et de l'Innovation (France), Institut National de la Santé et de la Recherche Médicale (France), Université Paris Cité, Center for Research for Influenza Pathogenesis (US), National Institute of Allergy and Infectious Diseases (US), Center of Excellence for Influenza Research and Response (US) CEIRR, Agencia Nacional de Investigación y Desarrollo (Chile), Centre National de la Recherche Scientifique (France), Ministère des Solidarités et de la Santé (France), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Fundación Mapfre, Sociedad Española de Neumología y Cirugía Torácica, Cabildo de Tenerife, Hellenic Foundation for Research and Innovation, Fondation pour la Recherche Médicale, Fondation Bettencourt Schueller, Ministerio de Ciencia, Innovación y Universidades (España), Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (España), Junta de Andalucía, Research Foundation - Flanders, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Etablissement Français du Sang [La Plaine Saint-Denis] (EFS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Laboratoire de Biotechnologie et Microbiologie Appliquée (LBMA), Université Bordeaux Segalen - Bordeaux 2-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR - laboratoire associé), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), 01057100, HORIZON-HLTH-2021-DISEASE-04, MESRI-COVID-19, ANR-10-LABX-62-IBEID, P18-RT-3320, CGIEU0000219140, RTC-2017-6471-1, REIPI RD16/0016/0009, National Institutes of Health, NIH: R01AI088364, R01AI163029, Howard Hughes Medical Institute, HHMI, National Institute of Allergy and Infectious Diseases, NIAID: 75N93021C00014, U19AI135972, U19AI142733, U19AI168631, Jeffrey Modell Foundation, JMF, Glenn Foundation for Medical Research, GFMR: ANRS-COV05, EA20170638020, EQU201903007798, Pfizer, Albert Ellis Institute, AEI, National Center for Advancing Translational Sciences, NCATS: UL1 TR001866, JPB Foundation, JPBF, Horizon 2020 Framework Programme, H2020: 824110, Fondation du Souffle, FdS, College of Natural Resources and Sciences, Humboldt State University, CNRS, Ministerio de Ciencia, Innovación y Universidades, MCIU, Instituto Tecnológico y de Energías Renovables, ITER, SCOR Corporate Foundation for Science, Agence Nationale de la Recherche, ANR: ANR-10-IAHU-01, Institut National de la Santé et de la Recherche Médicale, Inserm, Fondo Nacional de Desarrollo Científico y Tecnológico, FONDECYT: 1161971, 1212023, Association Nationale de la Recherche et de la Technologie, ANRT, Fonds Wetenschappelijk Onderzoek, FWO: G0B5120N, G0C8517N, G0E8420N, KU Leuven: C16/18/007, Instituto de Salud Carlos III, ISCIII: COV20_01333, COV20_01334, PI12/01565, European Regional Development Fund, ERDF: CB21/13/00006, University of the East, UE, Hellenic Foundation for Research and Innovation, ΕΛ.ΙΔ.Ε.Κ, Université de Paris, SINOVAC outside the submitted work. P. Retamar-Gentil reported personal fees from Merck outside the submitted work. I. Meyts reported grants from CSL-Behring outside the submitted work. E. Andreakos reported grants from Janssen Pharmaceuticals during the conduct of the study. J. Wauters reported grants and personal fees from Pfizer and Gilead outside the submitted work. L. Vanderbeke reported grants from Research Foundation Flanders and non-financial support from Pfizer outside the submitted work. S. Feys reported grants from Pfizer outside the submitted work. J. Casalegno reported 'other' from Pfizer and grants from Sanofi outside the submitted work. M. Rosa-Calatrava reported a patent to WO2016/146836 licensed (Signia Therapeutics), a patent to WO2017/174593 licensed (Signia Therapeutics), and a patent to WO2019/224489 licensed (Signia Therapeutics), and is the co-founder of Signia Therapeutics SAS. S. Trouillet-Assant reported non-financial support from BioMérieux outside the submitted work. A. Garcia-Sastre reported 'other' from Vivaldi Biosciences, Pagoda, Contrafect, Vaxalto, Accurius, Curelab oncology, and Curelab veterinary, personal fees from Avimex, 7Hills, Esperovax, Pfizer, Farmak, Applied Biological Laboratories, Paratus, Pharmamar, Pfizer, and Synairgen, grants from Pfizer, Pharmamar, Blade Therapeutics, Avimex, Accurius, Dyna-vax, Kenall Manufacturing, ImmunityBio, Nanocomposix, Merck, Model Medicines, Atea Pharma, Shenwa Biosciences, Johnson & Johnson, 7 Hills, Hexamer, N-fold LLC, and Applied Biological Laboratories outside the submitted work, in addition, A. Garcia-Sastre had a patent for influenza virus vaccines and uses thereof issued, and invited speaker in meeting events organized by Seqirus, Janssen, Abbott, and Astrazeneca. J. Casanova reported a patent to PCT/US2021/ 042741 pending. No other disclosures were reported., We thank Dr. Cato Jacobs for her contribution to the sampling of UZLeuven patients in Belgium. The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH, R01AI088364 and R01AI163029), the National Center for Advancing Translational Sciences, NIH Clinical and Translational Science Award program (UL1 TR001866), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, the French National Research Agency (ANR) under the 'Investments for the Future' program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (EQU201903007798), the ANRS-COV05, ANR-RHU program ANR-21-RHUS-08, ANR GENVIR (ANR-20-CE93-003), ANR GenMISC (ANR-21-COVR-0039), and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the European Union’s Horizon 2020 research and innovation program under grant agreement 824110 (EASI-genomics), the HORIZON-HLTH-2021-DISEASE-04 program under grant agreement 01057100 (UNDINE), the Square Foundation, Grandir–Fonds de solidarité pour l’enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Sci-ence, the French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM, and the Université Paris Cité. This work was partly supported by the Center for Research on Influenza Pathogenesis and Transmis-sion, a National Institute of Allergy and Infectious Diseases (NIAID)–funded Center of Excellence for Influenza Research and Response (contract no. 75N93021C00014), and the FLUOMICS Consortium (NIH-NIAID grant U19AI135972) to both A. García-Sastre and R.A. Medina, and by NIAID grant U19AI142733 and U19AI168631 to A. García-Sastre. Work in the Medina laboratory was also supported by the PIA ACT 1408, FONDECYT 1161971 and 1212023 grants from Agencia Nacional de Investigación y De-sarrollo of Chile. The VirPath team is supported by INSERM REACTing (Research & Action Emerging Infectious Diseases), CNRS, and Mérieux Research grants. B. Padey is supported by an ANRT CIFRE PhD scholarship. For the Lyon cohort, specimen collection and study was supported by a grant from the French Ministry of Health PHRC-I 2013 ANTIGRIPPE. C. Rodríguez-Gallego and colleagues were supported by the Instituto de Salud Carlos III (COV20_01333, COV20_01334, and PI12/01565, Spanish Ministry for Science and Innovation RTC-2017-6471-1, AEI/ FEDER, UE), Grupo DISA, Fundación MAPFRE Guanarteme, Sociedad Española de Neumología y Cirugía Torácica and Cab-ildo Insular de Tenerife (CGIEU0000219140 and 'Apuestas, científicas del Instituto Tecnológico y de Energías Renovables para colaborar en la lucha contra la COVID-19'). E. Andreakos is supported by the Hellenic Foundation for Research and Innovation (INTERFLU, no. 1574). P. Bastard was supported by the French Foundation for Medical Research (EA20170638020) and by the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). This study was supported by Plan Nacional de I+D+i 2013-2016 and In-stituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009), cofinanced by European Regional Development Fund 'A way to achieve Eu-rope', Operative Program Intelligence Growth 2014-2020 (CB21/13/00006) also was supported by CIBER-Consorcio Centro de Investigación Biomédica en Red, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea–Next Generation EU and Consejería de Economía, Conocimiento, Empresas y Universidad, Secretaría General de Universidades, Investigación y Tecnología, Junta de Andalucía, Spain (P18-RT-3320). I. Meyts is a Senior Clinical Investigator at the Research Foundation–Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies, a CSL-Behring Research Grant, KU Leuven C1 grant C16/18/007, a VIB GC PID Grant, Fonds Wetenschappelijk Onderzoek grants G0C8517N, G0B5120N, and G0E8420N, and the Jeffrey Modell Foundation. Open Access funding provided by Rockefeller University. Author contributions: Q. Zhang, A. Pizzorno, L. Miorin, P., The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH, R01AI088364 and R01AI163029), the National Center for Advancing Translational Sciences, NIH Clinical and Translational Science Award program (UL1 TR001866), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, the French National Research Agency (ANR) under the 'Investments for the Future' program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (EQU201903007798), the ANRS-COV05, ANR-RHU program ANR-21-RHUS-08, ANR GENVIR (ANR-20-CE93-003), ANR GenMISC (ANR-21-COVR-0039), and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the European Union’s Horizon 2020 research and innovation program under grant agreement 824110 (EASI-genomics), the HORIZON-HLTH-2021-DISEASE-04 program under grant agreement 01057100 (UNDINE), the Square Foundation, Grandir–Fonds de solidarité pour l’enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, the French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM, and the Université Paris Cité. This work was partly supported by the Center for Research on Influenza Pathogenesis and Transmission, a National Institute of Allergy and Infectious Diseases (NIAID)–funded Center of Excellence for Influenza Research and Response (contract no. 75N93021C00014), and the FLUOMICS Consortium (NIH-NIAID grant U19AI135972) to both A. García-Sastre and R.A. Medina, and by NIAID grant U19AI142733 and U19AI168631 to A. García-Sastre. Work in the Medina laboratory was also supported by the PIA ACT 1408, FONDECYT 1161971 and 1212023 grants from Agencia Nacional de Investigación y De-sarrollo of Chile. The VirPath team is supported by INSERM REACTing (Research & Action Emerging Infectious Diseases), CNRS, and Mérieux Research grants. B. Padey is supported by an ANRT CIFRE PhD scholarship. For the Lyon cohort, specimen collection and study was supported by a grant from the French Ministry of Health PHRC-I 2013 ANTIGRIPPE. C. Rodríguez-Gallego and colleagues were supported by the Instituto de Salud Carlos III (COV20_01333, COV20_01334, and PI12/01565, Spanish Ministry for Science and Innovation RTC-2017-6471-1, AEI/ FEDER, UE), Grupo DISA, Fundación MAPFRE Guanarteme, Sociedad Española de Neumología y Cirugía Torácica and Cabildo Insular de Tenerife (CGIEU0000219140 and 'Apuestas, científicas del Instituto Tecnológico y de Energías Renovables para colaborar en la lucha contra la COVID-19'). E. Andreakos is supported by the Hellenic Foundation for Research and, Innovation (INTERFLU, no. 1574). P. Bastard was supported by the French Foundation for Medical Research (EA20170638020) and by the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). This study was supported by Plan Nacional de I+D+i 2013-2016 and In-stituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009), cofinanced by European Regional Development Fund 'A way to achieve Europe', Operative Program Intelligence Growth 2014-2020 (CB21/13/00006) also was supported by CIBER-Consorcio Centro de Investigación Biomédica en Red, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea–Next Generation EU and Consejería de Economía, Conocimiento, Empresas y Universidad, Secretaría General de Universidades, Investigación y Tecnología, Junta de Andalucía, Spain (P18-RT-3320). I. Meyts is a Senior Clinical Investigator at the Research Foundation–Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies, a CSL-Behring Research Grant, KU Leuven C1 grant C16/18/007, a VIB GC PID Grant, Fonds Wetenschappelijk Onderzoek grants G0C8517N, G0B5120N, and G0E8420N, and the Jeffrey Modell Foundation. Open Access funding provided by Rockefeller University., ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020), ANR-20-CE93-0003,GENVIR,Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères(2020), ANR-21-COVR-0039,GenMIS-C,Recherche des Déficits immunitaires innées monogéniques prédisposant au syndrome inflammatoire multisystémique chez l'enfant.(2021), and ANR-21-RHUS-0008,COVIFERON,Covid-19 and interferons: from discovery to therapy(2021)

Subjects
INTERFERON, Cerba HealthCare Group, Immunology, SEVERE COVID-19, Pneumònia, Autoanticossos, DETERMINANTS, IMMUNITY, Grip, NEUTRALIZING ANTIBODIES, 3C-Dijon Study, INFECTION, Influenza, Human, Medicine and Health Sciences, Immunology and Allergy, Humans, COVID Human Genetic Effort, MYASTHENIA-GRAVIS PATIENTS, Autoantibodies, REIPI INF Working Group, Etablissement Français du Sang Study Group, Yellow Fever Vaccine, COVID-19, Pneumonia, ALLELES, Lyon Antigrippe Working Group, Influenza, ALPHA, Settore MED/03, Interferon Type I, [SDV.IMM]Life Sciences [q-bio]/Immunology, BURDEN, Constances Cohort
Abstract

Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-α2 alone (five patients) or with IFN-ω (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-α2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-ω. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients 70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-α2 and IFN-ω (OR = 11.7, P = 1.3 × 10-5), especially those, The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH; R01AI088364 and R01AI163029), the National Center for Advancing Translational Sciences, NIH Clinical and Translational Science Award program (UL1 TR001866), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, the French National Research Agency (ANR) under the “Investments for the Future” program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (EQU201903007798), the ANRS-COV05, ANR-RHU program ANR-21-RHUS-08, ANR GENVIR (ANR-20-CE93-003), ANR GenMISC (ANR-21-COVR-0039), and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the European Union’s Horizon 2020 research and innovation program under grant agreement 824110 (EASI-genomics), the HORIZON-HLTH-2021-DISEASE-04 program under grant agreement 01057100 (UNDINE), the Square Foundation, Grandir–Fonds de solidarité pour l’enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, the French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM, and the Université Paris Cité. This work was partly supported by the Center for Research on Influenza Pathogenesis and Transmission, a National Institute of Allergy and Infectious Diseases (NIAID)–funded Center of Excellence for Influenza Research and Response (contract no. 75N93021C00014), and the FLUOMICS Consortium (NIH-NIAID grant U19AI135972) to both A. García-Sastre and R.A. Medina, and by NIAID grant U19AI142733 and U19AI168631 to A. García-Sastre. Work in the Medina laboratory was also supported by the PIA ACT 1408, FONDECYT 1161971 and 1212023 grants from Agencia Nacional de Investigación y Desarrollo of Chile. The VirPath team is supported by INSERM REACTing (Research & Action Emerging Infectious Diseases), CNRS, and Mérieux Research grants. B. Padey is supported by an ANRT CIFRE PhD scholarship. For the Lyon cohort, specimen collection and study was supported by a grant from the French Ministry of Health PHRC-I 2013 ANTIGRIPPE. C. Rodríguez-Gallego and colleagues were supported by the Instituto de Salud Carlos III (COV20_01333, COV20_01334, and PI12/01565, Spanish Ministry for Science and Innovation RTC-2017-6471-1; AEI/FEDER, UE), Grupo DISA, Fundación MAPFRE Guanarteme, Sociedad Española de Neumología y Cirugía Torácica and Cabildo Insular de Tenerife (CGIEU0000219140 and “Apuestas, científicas del Instituto Tecnológico y de Energías Renovables para colaborar en la lucha contra la COVID-19”). E. Andreakos is supported by the Hellenic Foundation for Research and Innovation (INTERFLU, no. 1574). P. Bastard was supported by the French Foundation for Medical Research (EA20170638020) and by the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). This study was supported by Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009); cofinanced by European Regional Development Fund “A way to achieve Europe”; Operative Program Intelligence Growth 2014-2020 (CB21/13/00006) also was supported by CIBER-Consorcio Centro de Investigación Biomédica en Red, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea–Next Generation EU and Consejería de Economía, Conocimiento, Empresas y Universidad, Secretaría General de Universidades, Investigación y Tecnología, Junta de Andalucía, Spain (P18-RT-3320). I. Meyts is a Senior Clinical Investigator at the Research Foundation–Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies, a CSL-Behring Research Grant, KU Leuven C1 grant C16/18/007, a VIB GC PID Grant, Fonds Wetenschappelijk Onderzoek grants G0C8517N, G0B5120N, and G0E8420N, and the Jeffrey Modell Foundation. Open Access funding provided by Rockefeller University.

Published
2022
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30. Prevalence and Risk Factors for Multidrug-Resistant Organisms Colonization in Long-Term Care Facilities Around the World: A Review

Author

Rodríguez-Villodres, Ángel, Martín-Gandul, Cecilia, Peñalva, Germán, Guisado-Gil, Ana Belén, Crespo-Rivas, Juan Carlos, Pachón-Ibáñez, María Eugenia, Lepe, José Antonio, Cisneros, José Miguel, [Rodríguez-Villodres,A, Martín-Gandul,C, Peñalva,G, Guisado-Gil,AB, Crespo-Rivas,JC, Pachón-Ibáñez,ME, Lepe,JA, Cisneros,JM] Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), University of Seville/CSIC/University Hospital Virgen del Rocío, Seville, Spain. [Guisado-Gil,AB] Department of Pharmacy, University Hospital Virgen del Rocío, Seville, Spain., and The study was funded by the Instituto de Salud Carlos III, the Spanish Ministry of Economy, Industry, and Competitiveness (grant number: PI17-02195) and was partially funded by the European Development Regional Fund 'A way to achieve Europe'. A.R.V. and A.B.G.G. are supported by the Subprograma Río Hortega, Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spain. A.R.V. grant number: CM18/00122. A.B.G.G. grant number: CM19/00029. C.M.G. and J.C.C.R. are supported by the Instituto de Salud Carlos III (grant number: PI17-02195) and co-financed by European Development Regional Fund ‘A way to achieve Europe’ ERDF, Spanish Network for the Research in Infectious Diseases (REIPI RD16/0016/0009).G.P. is supported by the Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001)- co-financed by European Development Regional Fund 'A way to achieve Europe', Operative program Intelligent Growth 2014–2020. M.E.P.I. is a postdoctoral researcher belonging to the program 'Nicolás Monardes' (C1-0038-2019), Servicio Andaluz de Salud, Junta de Andalucía, Spain. J.M.C. received funding for research from Plan Nacional de I+D+i 2013–2016 and Instituto de Salud Carlos III, Subdireccion General de Redes y Centros de InvestigacionCooperativa, Ministry of Economy, Industry and Competitiveness, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001, RD16/0016/0009), co-financed by the European Development Regional Fund 'A way to achieve Europe'.

Subjects
Acinetobacter baumannii, Geographical Locations::Geographic Locations::Americas::North America [Medical Subject Headings], Cuidados a largo plazo, Staphylococcus aureus resistente a meticilina, Nursing homes, Check Tags::Male [Medical Subject Headings], Antimicrobial stewardship, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Organisms::Bacteria::Gram-Negative Bacteria::Gram-Negative Aerobic Bacteria::Gram-Negative Aerobic Rods and Cocci::Moraxellaceae::Acinetobacter::Acinetobacter baumannii [Medical Subject Headings], Prevalence, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Patient Care::Long-Term Care [Medical Subject Headings], Geographical Locations::Geographic Locations::Asia [Medical Subject Headings], Casas de salud, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Morbidity::Prevalence [Medical Subject Headings], Programas de optimización del uso de los antimicrobianos, Organisms::Bacteria::Endospore-Forming Bacteria::Gram-Positive Endospore-Forming Bacteria::Gram-Positive Endospore-Forming Rods::Staphylococcaceae::Staphylococcus::Staphylococcus aureus::Methicillin-Resistant Staphylococcus aureus [Medical Subject Headings], Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Multidrug-resistant organism, Organisms::Bacteria::Gram-Negative Bacteria::Gram-Negative Aerobic Bacteria::Gram-Negative Aerobic Rods and Cocci::Pseudomonadaceae::Pseudomonas::Pseudomonas aeruginosa [Medical Subject Headings], Long term care facilities, Phenomena and Processes::Microbiological Phenomena::Bacterial Physiological Phenomena::Drug Resistance, Bacterial::Drug Resistance, Multiple, Bacterial [Medical Subject Headings], Risk factors, Chemicals and Drugs::Carbohydrates::Glycoconjugates::Glycopeptides::Vancomycin [Medical Subject Headings], Pseudomonas aeruginosa, Information Science::Information Science::Information Storage and Retrieval::Databases as Topic::Databases, Bibliographic::PubMed [Medical Subject Headings], Information Science::Information Science::Communications Media::Publications::Bibliography as Topic::Bibliometrics [Medical Subject Headings], Methicillin-resistant staphylococcus aureus, Organisms::Bacteria::Gram-Positive Bacteria::Lactobacillales::Enterococcaceae::Enterococcus [Medical Subject Headings], Prevalencia, Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams::Carbapenems [Medical Subject Headings], Enterococcus, Factores de riesgo, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Anti-Bacterial Agents [Medical Subject Headings]
Abstract

Elderly people confined to chronic care facilities face an increased risk of acquiring infections by multidrug-resistant organisms (MDROs). This review presents the current knowledge of the prevalence and risk factors for colonization by MDROs in long-term care facilities (LTCF), thereby providing a useful reference to establish objectives for implementing successful antimicrobial stewardship programs (ASPs). We searched in PubMed and Scopus for studies examining the prevalence of MDROs and/or risk factors for the acquisition of MDROs in LTCF. One hundred and thirty-four studies published from 1987 to 2020 were included. The prevalence of MDROs in LTCF varies between the different continents, where Asia reported the highest prevalence of extended-spectrum ß-lactamase (ESBL) Enterobacterales (71.6%), carbapenem resistant (CR) Enterobacterales (6.9%) and methicillin-resistant Staphylococcus aureus (MRSA) (25.6%) and North America the highest prevalence to MDR Pseudomonas aeruginosa (5.4%), MDR Acinetobacter baumannii (15.0%), vancomycin-resistant Enterococcus spp. (VRE) (4.0%), and Clostridioides difficile (26.1%). Furthermore, MDRO prevalence has experienced changes over time, with increases in MDR P. aeruginosa and extended spectrum ß-lactamase producing Enterobacterales observed starting in 2015 and decreases of CR Enterobacterales, MDR A. baumannii, VRE, MRSA and C. difficile. Several risk factors have been found, such as male sex, chronic wounds, the use of medical devices, and previous antibiotic use. The last of these aspects represents one of the most important modifiable factors for reducing colonization with MDROs through implementing ASPs in LTCF. Yes

Published
2021

31. Prevalence and Risk Factors for Multidrug-Resistant Organisms Colonization in Long-Term Care Facilities Around the World: A Review

Author

Juan Carlos Crespo-Rivas, Germán Peñalva, Cecilia Martín-Gandul, Ana Belén Guisado-Gil, María Eugenia Pachón-Ibáñez, José Antonio Lepe, Ángel Rodríguez-Villodres, José Miguel Cisneros, Universidad de Sevilla. Departamento de Microbiología, Universidad de Sevilla. Departamento de Medicina, European Development Regional Fund 'A way to achieve Europe' ERDF, Spanish Network for the Research in Infectious Diseases, REIPI RD16/0016/0009, European Development Regional Fund 'A way to achieve Europe', European Development Regional Fund 'A way to achieve Europe', Operative program Intelligent Growth 2014-2020, Instituto de Salud Carlos III, PI17-02195, Instituto de Salud Carlos III, Subdireccion General de Redes y Centros de Investigacion Cooperativa, Ministerio de Economia, Industria y Competitividad, Spanish Network for Research in Infectious Diseases, REIPI RD16/0016/0001, Instituto de Salud Carlos III, Subdireccion General de Redes y Centros de InvestigacionCooperativa, Ministry of Economy, Industry and Competitiveness, Spanish Network for Research in Infectious Diseases, REIPI RD16/0016/0001, RD16/0016/0009, Instituto de Salud Carlos III, the Spanish Ministry of Economy, Industry, and Competitiveness, PI17-02195, Plan Nacional de I+D+i 2013-2016, Servicio Andaluz de Salud, Junta de Andalucia, Spain, C1-0038-2019, and Subprograma Rio Hortega, Instituto de Salud Carlos III, Subdireccion General de Redes y Centros de Investigacion Cooperativa, Ministerio de Ciencia, Innovacion y Universidades, Spain

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, 030106 microbiology, prevalence, Review, RM1-950, nursing homes, medicine.disease_cause, Biochemistry, Microbiology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Antimicrobial stewardship, risk factors, Pharmacology (medical), Colonization, 030212 general & internal medicine, General Pharmacology, Toxicology and Pharmaceutics, Chronic care, biology, business.industry, Pseudomonas aeruginosa, multidrug-resistant organism, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, Acinetobacter baumannii, Multiple drug resistance, Long-term care, antimicrobial stewardship, Infectious Diseases, Increased risk, long term care facilities, Therapeutics. Pharmacology, business
Abstract

Elderly people confined to chronic care facilities face an increased risk of acquiring infections by multidrug-resistant organisms (MDROs). This review presents the current knowledge of the prevalence and risk factors for colonization by MDROs in long-term care facilities (LTCF), thereby providing a useful reference to establish objectives for implementing successful antimicrobial stewardship programs (ASPs). We searched in PubMed and Scopus for studies examining the prevalence of MDROs and/or risk factors for the acquisition of MDROs in LTCF. One hundred and thirty-four studies published from 1987 to 2020 were included. The prevalence of MDROs in LTCF varies between the different continents, where Asia reported the highest prevalence of extended-spectrum ß-lactamase (ESBL) Enterobacterales (71.6%), carbapenem resistant (CR) Enterobacterales (6.9%) and methicillin-resistant Staphylococcus aureus (MRSA) (25.6%) and North America the highest prevalence to MDR Pseudomonas aeruginosa (5.4%), MDR Acinetobacter baumannii (15.0%), vancomycin-resistant Enterococcus spp. (VRE) (4.0%), and Clostridioides difficile (26.1%). Furthermore, MDRO prevalence has experienced changes over time, with increases in MDR P. aeruginosa and extended spectrum ß-lactamase producing Enterobacterales observed starting in 2015 and decreases of CR Enterobacterales, MDR A. baumannii, VRE, MRSA and C. difficile. Several risk factors have been found, such as male sex, chronic wounds, the use of medical devices, and previous antibiotic use. The last of these aspects represents one of the most important modifiable factors for reducing colonization with MDROs through implementing ASPs in LTCF.

Published
2021

32. Periprosthetic Joint Infection Prophylaxis in the Elderly after Hip Hemiarthroplasty in Proximal Femur Fractures: Insights and Challenges

Author

Carles Pigrau, P. Corona, Benito Almirante, Júlia Sellarès-Nadal, Laura Escolà-Vergé, Dolors Rodríguez-Pardo, Institut Català de la Salut, [Rodríguez-Pardo D] Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0003), Instituto de Salud Carlos III, 28029 Madrid, Spain. Study Group on Osteoarticular Infections of the Spanish Society of Clinical Microbiology and Infectious Diseases (GEIO-SEIMC), 28003 Madrid, Spain. Medicina Interna, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Escolà-Vergé L, Pigrau C] Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0003), Instituto de Salud Carlos III, 28029 Madrid, Spain. Study Group on Osteoarticular Infections of the Spanish Society of Clinical Microbiology and Infectious Diseases (GEIO-SEIMC), 28003 Madrid, Spain. [Sellarès-Nadal J] Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Study Group on Osteoarticular Infections of the Spanish Society of Clinical Microbiology and Infectious Diseases (GEIO-SEIMC), 28003 Madrid, Spain. Medicina Interna, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Corona PS] Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0003), Instituto de Salud Carlos III, 28029 Madrid, Spain. Study Group on Osteoarticular Infections of the Spanish Society of Clinical Microbiology and Infectious Diseases (GEIO-SEIMC), 28003 Madrid, Spain. Medicina Interna, Universitat Autònoma de Barcelona, Bellaterra, Spain. Unitat de Cirurgia Sèptica i Reconstructiva (UCSO), Servei de Cirurgia Ortopèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Almirante B] Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0003), Instituto de Salud Carlos III, 28029 Madrid, Spain. Medicina Interna, Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
0301 basic medicine, Infeccions quirúrgiques, Antibiotics, Cefazolin, Periprosthetic, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Otros calificadores::Otros calificadores::/efectos adversos [Otros calificadores], Biochemistry, 0302 clinical medicine, Decolonization, Periprosthetic joint infection, Pharmacology (medical), 030212 general & internal medicine, General Pharmacology, Toxicology and Pharmaceutics, Antibiotic prophylaxis, periprosthetic joint infection, antibiotic prophylaxis, intervenciones quirúrgicas::procedimientos ortopédicos::artroplastia::artroplastia de sustitución::hemiartroplastia [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Articulacions artificials, Antimicrobial, Glycopeptide, Infectious Diseases, Perspective, medicine.drug, Microbiology (medical), medicine.medical_specialty, medicine.drug_class, 030106 microbiology, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Proximal femur fracture, Microbiology, 03 medical and health sciences, Internal medicine, medicine, Malalties bacterianes - Tractament, Bacterial Infections and Mycoses::Infection::Prosthesis-Related Infections [DISEASES], Other subheadings::Other subheadings::/adverse effects [Other subheadings], business.industry, proximal femur fracture, Hip hemiarthroplasty, lcsh:RM1-950, infecciones bacterianas y micosis::infección::infecciones relacionadas con prótesis [ENFERMEDADES], Clindamycin, Surgical Procedures, Operative::Orthopedic Procedures::Arthroplasty::Arthroplasty, Replacement::Hemiarthroplasty [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], lcsh:Therapeutics. Pharmacology, hip hemiarthroplasty, decolonization, business
Abstract

Profilaxi antibiòtica; Hemiartroplàstia de maluc; Infecció periprotèsica de l'articulació Profilaxis antibiótica; Hemiartroplastia de cadera; Infección de la articulación periprotésica Antibiotic prophylaxis; Hip hemiarthroplasty; Periprosthetic joint infection We review antibiotic and other prophylactic measures to prevent periprosthetic joint infection (PJI) after hip hemiarthroplasty (HHA) surgery in proximal femoral fractures (PFFs). In the absence of specific guidelines, those applied to these individuals are general prophylaxis guidelines. Cefazolin is the most widely used agent and is replaced by clindamycin or a glycopeptide in beta-lactam allergies. A personalized antibiotic scheme may be considered when colonization by a multidrug-resistant microorganism (MDRO) is suspected. Particularly in methicillin-resistant Staphylococcus aureus (MRSA) colonization or a high prevalence of MRSA-caused PJIs a glycopeptide with cefazolin is recommended. Strategies such as cutaneous decolonization of MDROs, mainly MRSA, or preoperative asymptomatic bacteriuria treatment have also been addressed with debatable results. Some areas of research are early detection protocols in MDRO colonizations by polymerase-chain-reaction (PCR), the use of alternative antimicrobial prophylaxis, and antibiotic-impregnated bone cement in HHA. Given that published evidence addressing PJI prophylactic strategies in PFFs requiring HHA is scarce, PJIs can be reduced by combining different prevention strategies after identifying individuals who will benefit from personalized prophylaxis. This work was supported by the ISCIII-Subdirección General de Evaluación y Fomento de la Investigación, through the project PI15/02161 and by the Plan Nacional de I+D+i 2013-016 and ISCIIII, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economia, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0003)-co-financed by European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 2014–2020.

Published
2021

33. Candida Periprosthetic Joint Infection: Is It Curable?

Author

Dolors Rodríguez-Pardo, P. Corona, Carles Pigrau, Laura Escolà-Vergé, Institut Català de la Salut, [Escolà-Vergé L, Rodríguez-Pardo D, Pigrau C] Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0003), Instituto de Salud Carlos III, 28029 Madrid, Spain. Study Group on Osteoarticular Infections of the Spanish Society of Clinical Microbiology and Infectious Diseases (GEIO-SEIMC), 28003 Madrid, Spain. [Corona PS] Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0003), Instituto de Salud Carlos III, 28029 Madrid, Spain. Study Group on Osteoarticular Infections of the Spanish Society of Clinical Microbiology and Infectious Diseases (GEIO-SEIMC), 28003 Madrid, Spain. Unitat de Cirurgia Sèptica i Reconstructiva, Servei de Cirurgia Ortopèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
0301 basic medicine, Microbiology (medical), Antifungal, medicine.medical_specialty, medicine.drug_class, Candida spp, 030106 microbiology, Cement spacer, Periprosthetic, Candidiasi - Tractament, Two-stage exchange surgery, RM1-950, antifungal-loaded cement spacer, Biochemistry, Microbiology, biofilm, 03 medical and health sciences, 0302 clinical medicine, Antifungal-loaded cement spacer, two-stage exchange surgery, Antibiotic therapy, Bacterial Infections and Mycoses::Mycoses::Candidiasis [DISEASES], Pròtesis - Complicacions, Periprosthetic joint infection, Bacterial Infections and Mycoses::Infection::Prosthesis-Related Infections [DISEASES], Medicine, Pharmacology (medical), General Pharmacology, Toxicology and Pharmaceutics, Intensive care medicine, Otros calificadores::/terapia [Otros calificadores], Fungus, 030222 orthopedics, Surgical approach, periprosthetic joint infection, business.industry, Biofilm, fungus, infecciones bacterianas y micosis::infección::infecciones relacionadas con prótesis [ENFERMEDADES], infecciones bacterianas y micosis::micosis::candidiasis [ENFERMEDADES], Other subheadings::/therapy [Other subheadings], Chronic infection, Infectious Diseases, Perspective, Therapeutics. Pharmacology, business
Abstract

Fong; Infecció articular periprotèsica; Cirurgia d'intercanvi en dues etapes Hongo; Infección de la articulación periprotésica; Cirugía de recambio en dos etapas Fungus; Periprosthetic joint infection; Two-stage exchange surgery Candida periprosthetic joint infection (CPJI) is a rare and very difficult to treat infection, and high-quality evidence regarding the best management is scarce. Candida spp. adhere to medical devices and grow forming biofilms, which contribute to the persistence and relapse of this infection. Typically, CPJI presents as a chronic infection in a patient with multiple previous surgeries and long courses of antibiotic therapy. In a retrospective series of cases, the surgical approach with higher rates of success consists of a two-stage exchange surgery, but the best antifungal treatment and duration of antifungal treatment are still unclear, and the efficacy of using an antifungal agent-loaded cement spacer is still controversial. Until more evidence is available, focusing on prevention and identifying patients at risk of CPJI seems more than reasonable. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Published
2021

34. Sterilization Procedure for Temperature-Sensitive Hydrogels Loaded with Silver Nanoparticles for Clinical Applications

Author

Institut Català de la Salut, [Rafael D] Grup Drug Delivery & Targeting (DDT), Vall d’Hebron Institut de Recerca, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. Networking Research Centre for Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III, Madrid, Spain. [Andrade F] Grup Drug Delivery & Targeting (DDT), Vall d’Hebron Institut de Recerca, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal. INEB-Instituto Nacional de Engenharia Biomédica, Universidade do Porto, Porto, Portugal. [Martinez-Trucharte F] Grup Drug Delivery & Targeting (DDT), Vall d’Hebron Institut de Recerca, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [Basas J] Laboratori de Resistencia Antimicrobiana, Vall d’Hebron Institut de Recerca, Barcelona, Spain. Servei de Malalties Infeccioses, Hospital Universitari Vall d'Hebron, Barcelona, Spain. Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0003), Instituto de Salud Carlos III, Madrid, Spain. [Seras-Franzoso J] Grup Drug Delivery & Targeting (DDT), Vall d’Hebron Institut de Recerca, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [Palau M] Laboratori de Resistencia Antimicrobiana, Vall d’Hebron Institut de Recerca, Barcelona, Spain. Servei de Malalties Infeccioses, Hospital Universitari Vall d'Hebron, Barcelona, Spain. Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0003), Instituto de Salud Carlos III, Madrid, Spain. [Gomis X] Laboratori de Resistència Antimicrobiana, Vall d’Hebron Institut de Recerca, Barcelona, Spain. Servei de Malalties Infeccioses, Hospital Universitari Vall d'Hebron, Barcelona, Spain. [Pérez-Burgos M] Grup Drug Delivery & Targeting (DDT), Vall d’Hebron Institut de Recerca, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [Blanco A] Servei de Cirurgia Ortopèdica, Hospital Universitari Vall d'Hebron, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. Grup en Enginyeria tissular musculoesquelètica, Vall d’Hebron Institut de Recerca, Barcelona, Spain. [López-Fernández A] Grup en Enginyeria tissular musculoesquelètica, Vall d’Hebron Institut de Recerca, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [Vélez R] Servei de Cirurgia Ortopèdica, Hospital Universitari Vall d'Hebron, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. Grup en Enginyeria tissular musculoesquelètica, Vall d’Hebron Institut de Recerca, Barcelona, Spain. [Abasolo I] Grup Drug Delivery & Targeting (DDT), Vall d’Hebron Institut de Recerca, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. Networking Research Centre for Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III, Madrid, Spain. [Aguirre M] Servei de Cirugia Ortopedica, Hospital Universitari Vall d'Hebron, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [Gavaldà J] Laboratori de Resistencia Antimicrobiana, Vall d’Hebron Institut de Recerca, Barcelona, Spain. Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0003), Instituto de Salud Carlos III, Madrid, Spain. [Schwartz S Jr] Grup Drug Delivery & Targeting (DDT), Vall d’Hebron Institut de Recerca, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. Networking Research Centre for Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III, Madrid, Spain., and Hospital Universitari Vall d'Hebron

Subjects
Col·loides, Complex Mixtures::Colloids::Gels::Hydrogels [CHEMICALS AND DRUGS], Other subheadings::Other subheadings::/prevention & control [Other subheadings], Mezclas Complejas::Coloides::Geles::Hidrogeles [COMPUESTOS QUÍMICOS Y DROGAS], Otros calificadores::Otros calificadores::/prevención & control [Otros calificadores], Other subheadings::/methods [Other subheadings], Environment and Public Health::Public Health::Public Health Practice::Communicable Disease Control::Infection Control::Sterilization [HEALTH CARE], Bacterial Infections and Mycoses::Infection [DISEASES], Otros calificadores::/métodos [Otros calificadores], ambiente y salud pública::salud pública::práctica de la salud pública::control de enfermedades transmisibles::control de infecciones::esterilización [ATENCIÓN DE SALUD], Esterilització, Infecció - Prevenció, Infecciones Bacterianas y Micosis::Infección [ENFERMEDADES]
Published
2021

35. Clinical characteristics and outcome of bacteraemia caused by Enterobacter cloacae and Klebsiella aerogenes: more similarities than differences

Author

Jorge Calvo-Montes, Rosario Lara-Contreras, Julián Torre-Cisneros, María Eliecer Cano-García, Miquel Pujol-Rojo, José Antonio Lepe, Fernando Rodríguez-López, Luis Martínez-Martínez, Fe Tubau-Quintano, Rocío Álvarez-Marín, Manuel E. Jiménez-Mejías, Jesús Rodríguez-Baño, Álvaro Pascual-Hernández, Cecilia Martín-Gandul, José-Manuel Rodríguez-Martínez, Oriol Gasch-Blasi, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Ministerio de Ciencia, Innovación y Universidades (España), Red Española de Investigación en Patología Infecciosa, European Commission, Spanish Network for Research in Infectious Diseases/Enterobacter spp. Bacteriemia Project Group, [Álvarez-Marín,R, Lepe,JA, Martín-Gandul,C, Jiménez-Mejías,ME] Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Infectious Diseases Research Group, Institute of Biomedicine of Seville (IBiS), University of Seville/CSIC/Virgen del Rocío University Hospital, Seville, Spain. [Gasch-Blasi,O] Infectious Diseases Service, Hospital Universitari Parc Taulí, Institut d'Investigació i Innovació Parc Taulí (l3PT), Sabadell, Spain, Spanish Network for Research in Infectious Diseases. [Rodríguez-Martínez,JM, Pascual-Hernández,Á] Department of Microbiology, Virgen Macarena University Hospital, Seville, Spain, Infectious Diseases Research Group, Institute of Biomedicine of Seville (IBiS), University of Seville/CSIC, Seville, Spain. [Calvo-Montes,J, Cano-García,ME, Martínez-Martínez,L] Department of Microbiology, Marqués de Valdecilla University Hospital – IDIVAL, Santander, Spain. [Lara-Contreras,R, Torre-Cisneros,J] Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Clinical Unit of Infectious Diseases, Reina Sofia University Hospital, University of Cordoba, Córdoba, Spain. [Tubau-Quintano,F] Department of Microbiology, University Hospital of Bellvitge, Barcelona, Spain, CIBER of Respiratory Diseases (CIBERes), Instituto de Salud Carlos III, Madrid, Spain. [Rodríguez-López,F] Department of Microbiology, Reina Sofía University Hospital, Maimonides Biomedical Research Institute of Cordoba (IMIBIC)/University of Cordoba, Córdoba, Spain. [Rodríguez-Baño,J] Department of Medicine, Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Virgen Macarena University Hospital, Institute of Biomedicine of Seville (IBiS), University of Seville/CSIC, Seville, Spain. [Pujol-Rojo,M] Department of Infectious Diseases, Hospital Universitari de Bellvitge, Institut Català de la Salut (ICS-HUB), Spanish Network for Research in Infectious Diseases (REIPI RD12/0015), Instituto de Salud Carlos III (ISCIII), Madrid, Spain, Institut d'Investigació Biomédica de Bellvitge (IDIBELL), Barcelona, Spain. [Martínez-Martínez,L] Department of Molecular Biology, University of Cantabria, Santander, Spain. [Martínez-Martínez,L] Department of Microbiology, Reina Sofía University Hospital, Maimonides Biomedical Research Institute of Cordoba (IMIBIC)/University of Cordoba, Córdoba, Spain., This work was supported by the Instituto Carlos III [grant PS09/00916], Ministerio de Ciencia e Innovación, the Plan Nacional I+D+i 2013–2016 and Instituto Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases [REIPI, RD16/0016/0001, RD16/0016/0005, RD16/0016/0007, RD16/0016/0008, and RD16/0016/0009], co-financed by the European Regional Development Fund ‘A way to achieve Europe’, Operative program Intelligent Growth 2014–2020.

Subjects
Quinolone resistance mechanism, 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Case–control study, medicine.drug_class, 030106 microbiology, Immunology, Antibiotics, Bacteremia, Enterobacter aerogenes, Microbiology, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Klebsiella aerogenes, Genotype, Enterobacter cloacae, medicine, Immunology and Allergy, Humans, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Organisms::Bacteria::Gram-Negative Bacteria::Gram-Negative Facultatively Anaerobic Rods::Enterobacteriaceae::Enterobacter::Enterobacter aerogenes [Medical Subject Headings], Estudios de casos y controles, biology, business.industry, Diseases::Bacterial Infections and Mycoses::Bacterial Infections::Bacteremia [Medical Subject Headings], Incidence (epidemiology), Case-control study, Enterobacteriaceae Infections, bacterial infections and mycoses, biology.organism_classification, QR1-502, Diseases::Bacterial Infections and Mycoses::Bacterial Infections::Gram-Negative Bacterial Infections::Enterobacteriaceae Infections [Medical Subject Headings], Multiple drug resistance, Organisms::Bacteria::Gram-Negative Bacteria::Gram-Negative Facultatively Anaerobic Rods::Enterobacteriaceae::Enterobacter::Enterobacter cloacae [Medical Subject Headings], Bacteriemia, Bacteraemia, business
Abstract

Spanish Network for Research in Infectious Diseases/Enterobacter spp. Bacteriemia Project Group., [Objectives] The genus Enterobacter is a common cause of nosocomial infections. Historically, the most frequent Enterobacter species were those of Enterobacter cloacae complex and Enterobacter aerogenes. In 2019, E. aerogenes was re-classified as Klebsiella aerogenes owing to its higher genotypic similarity with the genus Klebsiella. Our objective was to characterise and compare the clinical profiles of bacteraemia caused by E. cloacae and K. aerogenes., [Methods] This 3-year multicentre, prospective cohort study enrolled consecutive patients with bacteraemia by E. cloacae or K. aerogenes. Baseline characteristics, bacteraemia features (source, severity, treatment), antibiotic susceptibility, resistance mechanisms and mortality were analysed. bacteraemia had received more antibiotics., [Results] The study included 285 patients with bacteraemia [196 (68.8%) E. cloacae and 89 (31.2%) K. aerogenes]. The groups showed no differences in age, sex, previous use of invasive devices, place of acquisition, sources or severity at onset. The Charlson score was higher among patients with E. cloacae bacteraemia [2 (1–4) vs. 1 (0.5–3); P = 0.018], and previous antibiotic therapy was more common in patients with K. aerogenes bacteraemia (57.3% vs. 41.3%; P = 0.01). Mortality was 19.4% for E. cloacae and 20.2% for K. aerogenes (P = 0.869). Antibiotic susceptibility was similar for both species, and the incidence of multidrug resistance or ESBL production was low (6% and 5.3%, respectively), with no differences between species., [Conclusion] Bacteraemias caused by E. cloacae and K. aerogenes share similar patient profiles, presentation and prognosis. Patients with E. cloacae bacteraemia had more co-morbidities and those with K. aerogenes bacteraemia had received more antibiotics., This work was supported by the Instituto Carlos III [grant PS09/00916], Ministerio de Ciencia e Innovación, the Plan Nacional I+D+i 2013–2016 and Instituto Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases [REIPI, RD16/0016/0001; RD16/0016/0005; RD16/0016/0007; RD16/0016/0008; RD16/0016/0009], co-financed by the European Regional Development Fund ‘A way to achieve Europe’, Operative program Intelligent Growth 2014–2020.

Published
2020

36. Oral Antibiotic Prophylaxis Lowers Surgical Site Infection in Elective Colorectal Surgery: Results of a Pragmatic Cohort Study in Catalonia

Author

Josep M. Badia, Miriam Flores-Yelamos, Ana Vázquez, Nares Arroyo-García, Mireia Puig-Asensio, David Parés, Miguel Pera, Joaquín López-Contreras, Enric Limón, Miquel Pujol, Members of the VINCat Colorectal Surveillance Team, [Badia JM, Flores-Yelamos M, Arroyo-García N] Department of Surgery, Hospital General Granollers, Granollers, Spain. School of Medicine, Universitat Internacional de Catalunya, Sant Cugat del Vallès, Barcelona, Spain. [Vázquez A] Servei d’Estadística Aplicada, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain. [Puig-Asensio M] Department of Infectious Diseases, Hospital Universitari de Bellvitge, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0005), L’Hospitalet del Llobregat, Spain. [Parés D] Department of Surgery, Hospital Universitari Germans Trias i Pujol, Badalona, Spain. [Pera M] Department of Surgery, Hospital del Mar, Barcelona, Spain. [López-Contreras J] Infectious Disease Unit, Hospital de la Santa Creu i Sant Pau–Institut d’Investigació Biomèdica Sant Pau, Barcelona, Spain. [Limón E] VINCat Program, Barcelona, Spain. Universitat de Barcelona, Barcelona, Spain. [Pujol M] Department of Infectious Diseases, Hospital Universitari de Bellvitge, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0005), L’Hospitalet del Llobregat, Spain. VINCat Program, Barcelona, Spain, and Hospital General de Granollers

Subjects
Infeccions quirúrgiques, Multivariate analysis, Surgical wound infection, Còlon - Cirurgia, Logistic regression, Profilaxi antibiòtica oral, Therapeutics::Drug Therapy::Therapeutics::Drug Therapy::Premedication::Antibiotic Prophylaxis [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Cirugía colorrectal, Antibiotics, afecciones patológicas, signos y síntomas::procesos patológicos::complicaciones posoperatorias::infección de la herida quirúrgica [ENFERMEDADES], Antibiotic prophylaxis, Univariate analysis, Infecció del lloc quirúrgic, terapéutica::farmacoterapia::terapéutica::farmacoterapia::premedicación::profilaxis antibiótica [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Preparación mecánica del intestino, Mesures preventives, General Medicine, surgical wound infection, Colorectal surgery, Pathological Conditions, Signs and Symptoms::Pathologic Processes::Postoperative Complications::Surgical Wound Infection [DISEASES], profesiones sanitarias::medicina::especialidades quirúrgicas::cirugía colorrectal [DISCIPLINAS Y OCUPACIONES], Medicine, Surgical site infection, Cohort study, medicine.medical_specialty, Cirurgia colorectal, mechanical bowel preparation, Antibiòtics, preventative measures, Article, Profilaxis antibiótica oral, Health Occupations::Medicine::Specialties, Surgical::Colorectal Surgery [DISCIPLINES AND OCCUPATIONS], Internal medicine, Infección del sitio quirúrgico, medicine, Infección de herida quirúrgica, business.industry, oral antibiotic prophylaxis, colorectal surgery, surgical site infection, Medidas preventivas, Infecció, Bowel preparation, Preparació mecànica de l'intestí, Infecció de la ferida quirúrgica, business
Abstract

Colorectal surgery; Mechanical bowel preparation; Oral antibiotic prophylaxis Cirugía colorrectal; Preparación mecánica del intestino; Profilaxis antibiótica oral Cirurgia colorrectal; Preparació mecànica de l'intestí; Profilaxi antibiòtica oral Background: The role of oral antibiotic prophylaxis (OAP) and mechanical bowel preparation (MBP) in the prevention of surgical site infection (SSI) after colorectal surgery is still controversial. The aim of this study was to analyze the effect of a bundle including both measures in a National Infection Surveillance Network in Catalonia. Methods: Pragmatic cohort study to assess the effect of OAP and MBP in reducing SSI rate in 65 hospitals, comparing baseline phase (BP: 2007-2015) with implementation phase (IP: 2016-2019). To compare the results, a logistic regression model was established. Results: Out of 34,421 colorectal operations, 5180 had SSIs (15.05%). Overall SSI rate decreased from 18.81% to 11.10% in BP and IP, respectively (OR 0.539, CI95 0.507-0.573, p < 0.0001). Information about bundle implementation was complete in 61.7% of cases. In a univariate analysis, OAP and MBP were independent factors in decreasing overall SSI, with OR 0.555, CI95 0.483-0.638, and OR 0.686, CI95 0.589-0.798, respectively; and similarly, organ/space SSI (O/S-SSI) (OR 0.592, CI95 0.494-0.710, and OR 0.771, CI95 0.630-0.944, respectively). However, only OAP retained its protective effect at both levels at multivariate analyses. Conclusions: oral antibiotic prophylaxis decreased the rates of SSI and O/S-SSI in a large series of elective colorectal surgery.

Published
2021
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37. Sterilization Procedure for Temperature-Sensitive Hydrogels Loaded with Silver Nanoparticles for Clinical Applications

Author

Joaquin Seras-Franzoso, Alberto Blanco, Simó Schwartz, Fernanda Andrade, Marc Pérez-Burgos, Roberto Vélez, Alba López-Fernández, Ibane Abasolo, Francesc Martinez-Trucharte, Marta Palau, Diana Rafael, Jana Basas, Marius Aguirre, Joan Gavaldà, Xavier Gomis, Instituto de Investigação e Inovação em Saúde, Institut Català de la Salut, [Rafael D] Grup Drug Delivery & Targeting (DDT), Vall d’Hebron Institut de Recerca, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. Networking Research Centre for Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III, Madrid, Spain. [Andrade F] Grup Drug Delivery & Targeting (DDT), Vall d’Hebron Institut de Recerca, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal. INEB-Instituto Nacional de Engenharia Biomédica, Universidade do Porto, Porto, Portugal. [Martinez-Trucharte F] Grup Drug Delivery & Targeting (DDT), Vall d’Hebron Institut de Recerca, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [Basas J] Laboratori de Resistencia Antimicrobiana, Vall d’Hebron Institut de Recerca, Barcelona, Spain. Servei de Malalties Infeccioses, Hospital Universitari Vall d'Hebron, Barcelona, Spain. Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0003), Instituto de Salud Carlos III, Madrid, Spain. [Seras-Franzoso J] Grup Drug Delivery & Targeting (DDT), Vall d’Hebron Institut de Recerca, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [Palau M] Laboratori de Resistencia Antimicrobiana, Vall d’Hebron Institut de Recerca, Barcelona, Spain. Servei de Malalties Infeccioses, Hospital Universitari Vall d'Hebron, Barcelona, Spain. Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0003), Instituto de Salud Carlos III, Madrid, Spain. [Gomis X] Laboratori de Resistència Antimicrobiana, Vall d’Hebron Institut de Recerca, Barcelona, Spain. Servei de Malalties Infeccioses, Hospital Universitari Vall d'Hebron, Barcelona, Spain. [Pérez-Burgos M] Grup Drug Delivery & Targeting (DDT), Vall d’Hebron Institut de Recerca, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [Blanco A] Servei de Cirurgia Ortopèdica, Hospital Universitari Vall d'Hebron, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. Grup en Enginyeria tissular musculoesquelètica, Vall d’Hebron Institut de Recerca, Barcelona, Spain. [López-Fernández A] Grup en Enginyeria tissular musculoesquelètica, Vall d’Hebron Institut de Recerca, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [Vélez R] Servei de Cirurgia Ortopèdica, Hospital Universitari Vall d'Hebron, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. Grup en Enginyeria tissular musculoesquelètica, Vall d’Hebron Institut de Recerca, Barcelona, Spain. [Abasolo I] Grup Drug Delivery & Targeting (DDT), Vall d’Hebron Institut de Recerca, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. Networking Research Centre for Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III, Madrid, Spain. [Aguirre M] Servei de Cirugia Ortopedica, Hospital Universitari Vall d'Hebron, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. [Gavaldà J] Laboratori de Resistencia Antimicrobiana, Vall d’Hebron Institut de Recerca, Barcelona, Spain. Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0003), Instituto de Salud Carlos III, Madrid, Spain. [Schwartz S Jr] Grup Drug Delivery & Targeting (DDT), Vall d’Hebron Institut de Recerca, Barcelona, Spain. Universitat Autònoma de Barcelona, Barcelona, Spain. Networking Research Centre for Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III, Madrid, Spain., and Vall d'Hebron Barcelona Hospital Campus

Subjects
Otros calificadores::Otros calificadores::/prevención & control [Otros calificadores], silver nanoparticles, Materials science, XDR strains, Other subheadings::/methods [Other subheadings], Sterilization procedure, General Chemical Engineering, Post-operative infecions, 02 engineering and technology, Chirurgic applications, Poloxamer, Post-operative infections, Silver nanoparticle, mezclas complejas::coloides::geles::hidrogeles [COMPUESTOS QUÍMICOS Y DROGAS], Autoclave, Complex Mixtures::Colloids::Gels::Hydrogels [CHEMICALS AND DRUGS], Other subheadings::Other subheadings::/prevention & control [Other subheadings], 03 medical and health sciences, anti-bacterial agents, Otros calificadores::/métodos [Otros calificadores], Anti-bacterial agents, General Materials Science, hydrogels, Col·loides, 0303 health sciences, 030306 microbiology, chirurgic applications, Sterilization, infecciones bacterianas y micosis::infección [ENFERMEDADES], Hydrogels, sterilization, Sterilization (microbiology), 021001 nanoscience & nanotechnology, Antimicrobial, Environment and Public Health::Public Health::Public Health Practice::Communicable Disease Control::Infection Control::Sterilization [HEALTH CARE], Bacterial Infections and Mycoses::Infection [DISEASES], Silver nanopaticles, ambiente y salud pública::salud pública::práctica de la salud pública::control de enfermedades transmisibles::control de infecciones::esterilización [ATENCIÓN DE SALUD], Esterilització, Drug delivery, Self-healing hydrogels, Temperature sensitive, Silver nanoparticles, Infecció - Prevenció, 0210 nano-technology, poloxamer, post-operative infections, Biomedical engineering
Abstract

Hydrogels (HG) have recognized benefits as drug delivery platforms for biomedical applications. Their high sensitivity to sterilization processes is however one of the greatest challenges regarding their clinical translation. Concerning infection diseases, prevention of post-operatory related infections is crucial to ensure appropriate patient recovery and good clinical outcomes. Silver nanoparticles (AgNPs) have shown good antimicrobial properties but sustained release at the right place is required. Thus, we produced and characterized thermo-sensitive HG based on Pluronic&reg, F127 loaded with AgNPs (HG-AgNPs) and their integrity and functionality after sterilization by dry-heat and autoclave methods were carefully assessed. The quality attributes of HG-AgNPs were seriously affected by dry-heat methods but not by autoclaving methods, which allowed to ensure the required sterility. Also, direct sterilization of the final HG-AgNPs product proved more effective than of the raw material, allowing simpler production procedures in non-sterile conditions. The mechanical properties were assessed in post mortem rat models and the HG-AgNPs were tested for its antimicrobial properties in vitro using extremely drug-resistant (XDR) clinical strains. The produced HG-AgNPs prove to be versatile, easy produced and cost-effective products, with activity against XDR strains and an adequate gelation time and spreadability features and optimal for in situ biomedical applications.

Published
2019

38. Neurological Complications of Infective Endocarditis

Author

Josefa Ruiz-Morales, José Manuel Lomas, Mariam Noureddine, Javier de la Torre-Lima, Francisco Javier Martínez-Marcos, Carmen Hidalgo-Tenorio, Antonio Plata, Radka Ivanova-Georgieva, Juan Gálvez-Acebal, Nuria Fernández-Hidalgo, J.M. Reguera, Benito Almirante, Arístides de Alarcón González, Emilio García-Cabrera, The Group for the Study of Cardiovascular Infections of the Andalusian Society of Infectious Diseases (SAEI) and the Spanish Network for Research in Infectious Diseases (REIPI), [García-Cabrera,E, Fernández-Hidalgo,N, Almirante,B, Ivanova-Georgieva,R, Noureddine,M, Plata,A, Lomas,ML, Gálvez-Acebal,J, Hidalgo-Tenorio,C, Ruíz-Morales,J, Martínez-Marcos,FJ, Reguera,JM, Torre-Lima,J De La, Alarcón González,A De] Spanish Network for Research in Infectious Diseases (REIPI), Seville, Spain. [García-Cabrera,E, Alarcón González,A De] Instituto de Biomedicina de Sevilla (IBIS) Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain. [Ivanova-Georgieva,R] Internal Medicine Unit, Hospital Universitario Virgen de la Victoria, Málaga, Spain. [Fernández-Hidalgo,N, Almirante,B] Diseases Department, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Medicine Department, Barcelona. [Ruíz-Morales,J] Infectious Diseases Service, Hospital Universitario Virgen de la Victoria, Malaga, Spain. [Noureddine,M] Infectious Diseases Unit Hospital Costa del Sol, Marbella, Malaga, Spain. [Plata,A, Ruíz-Morales,J] Infectious Diseases Service, Hospital Universitario Carlos Haya Malaga. [Lomas,JM, Martínez-Marcos,FJ] Infectious Diseases Unit Hospital Juan Ramón Jiménez, Huelva, Spain. [Gálvez-Acebal,J] Clinical Service of Infectious Disease and Clinical Microbiology, Hospital Universitario Virgen Macarena, Seville, Spain. [Hidalgo-Tenorio,C] Infectious Diseases Service, Hospital Universitario Virgen de las Nieves, Granada, Spain. [Alarcón González,A De] Infectious Diseases, Microbiology and Preventive Medicine Department, Hospital Universitario Virgen del Rocío, Seville, Spain., and This study was funded by the Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III, and cofinanced by the European Development Regional Fund 'A way to achieve Europe', Spanish Network for the Research in Infectious Diseases (REIPI RD06/0008).

Subjects
Male, Complications, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical::Proportional Hazards Models [Medical Subject Headings], Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Postoperative Complications [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies::Retrospective Studies [Medical Subject Headings], Hemorragia cerebral, Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Comorbidity, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Brain Ischemia, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Diseases::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Cerebrovascular Disorders::Intracranial Arterial Diseases::Intracranial Aneurysm [Medical Subject Headings], Postoperative Complications, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Clinical Trials as Topic::Multicenter Studies as Topic [Medical Subject Headings], Anti-Infective Agents, Risk Factors, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Epidemiologic Factors::Comorbidity [Medical Subject Headings], Diseases::Cardiovascular Diseases::Heart Diseases::Endocarditis [Medical Subject Headings], Infecciones estafilocócicas, Diseases::Nervous System Diseases::Central Nervous System Diseases::Meningitis [Medical Subject Headings], Multicenter Studies as Topic, Medicine, Antiinfecciosos, Absceso encefálico, Ultrasonography, Heart Valve Prosthesis Implantation, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Hematologic Agents::Anticoagulants [Medical Subject Headings], Diseases::Virus Diseases::Central Nervous System Viral Diseases::Encephalitis [Medical Subject Headings], Endocarditis, Incidence, Incidence (epidemiology), Hazard ratio, Pronóstico, Middle Aged, Staphylococcal Infections, Comorbilidad, Prognosis, Combined Modality Therapy, Cardiac surgery, Diseases::Bacterial Infections and Mycoses::Brain Abscess [Medical Subject Headings], Treatment Outcome, Infective endocarditis, Cohort, Encephalitis, Female, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents [Medical Subject Headings], Estudios de seguimiento, Aneurisma Intracraneal, Infection, Incidencia, Cardiology and Cardiovascular Medicine, Meningitis, Factores de riesgo, Nervous system, Adult, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Combined Modality Therapy [Medical Subject Headings], medicine.medical_specialty, Encephalopathy, Check Tags::Male [Medical Subject Headings], Brain Abscess, Estudios retrospectivos, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Morbidity::Incidence [Medical Subject Headings], Modelos de riesgos Proporcionales, Physiology (medical), Internal medicine, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Follow-Up Studies [Medical Subject Headings], Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], Humans, Estudios multicéntricos como Asunto, Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Diseases::Bacterial Infections and Mycoses::Bacterial Infections::Gram-Positive Bacterial Infections::Staphylococcal Infections [Medical Subject Headings], Isquemia encefálica, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment Outcome [Medical Subject Headings], Aged, Cerebral Hemorrhage, Proportional Hazards Models, Retrospective Studies, Terapia combinada, business.industry, Proportional hazards model, Diseases::Cardiovascular Diseases::Vascular Diseases::Cerebrovascular Disorders::Intracranial Hemorrhages::Cerebral Hemorrhage [Medical Subject Headings], Anticoagulants, Encefalitis, Intracranial Aneurysm, Complicaciones postoperatorias, medicine.disease, Surgery, Check Tags::Female [Medical Subject Headings], Spain, Diseases::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Cerebrovascular Disorders::Brain Ischemia [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis [Medical Subject Headings], Resultado del tratamiento, business, Endocardium, Follow-Up Studies
Abstract

Background— The purpose of this study was to assess the incidence of neurological complications in patients with infective endocarditis, the risk factors for their development, their influence on the clinical outcome, and the impact of cardiac surgery. Methods and Results— This was a retrospective analysis of prospectively collected data on a multicenter cohort of 1345 consecutive episodes of left-sided infective endocarditis from 8 centers in Spain. Cox regression models were developed to analyze variables predictive of neurological complications and associated mortality. Three hundred forty patients (25%) experienced such complications: 192 patients (14%) had ischemic events, 86 (6%) had encephalopathy/meningitis, 60 (4%) had hemorrhages, and 2 (1%) had brain abscesses. Independent risk factors associated with all neurological complications were vegetation size ≥3 cm (hazard ratio [HR] 1.91), Staphylococcus aureus as a cause (HR 2.47), mitral valve involvement (HR 1.29), and anticoagulant therapy (HR 1.31). This last variable was particularly related to a greater incidence of hemorrhagic events (HR 2.71). Overall mortality was 30%, and neurological complications had a negative impact on outcome (45% of deaths versus 24% in patients without these complications; P Conclusions— Moderate to severe ischemic stroke and brain hemorrhage were found to have a significant negative impact on the outcome of infective endocarditis. Early appropriate antimicrobial treatment is critical, and transitory discontinuation of anticoagulant therapy should be considered.

Published
2013
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39. Hyperthermia Prevents In Vitro and In Vivo Biofilm Formation on Endotracheal Tubes

Author

Marta Palau, Estela Muñoz, Nieves Larrosa, Xavier Gomis, Ester Márquez, Oscar Len, Benito Almirante, Joan Gavaldà, Institut Català de la Salut, [Palau M, Len O, Almirante B, Gavaldà J] Grup de Recerca de Microbiologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Muñoz E] Grup de Recerca de Microbiologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Larrosa N] Spanish Network for Research in Infectious Diseases (REIPI RD19/0016), Instituto de Salud Carlos III, Madrid, Spain. CIBERINFEC, ISCIII-CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain. Servei de Microbiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Gomis X] Grup de Recerca de Microbiologia, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. CIBERINFEC, ISCIII-CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain. [Márquez E] Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Microbiology (medical), Bacterial Infections and Mycoses::Infection::Cross Infection::Pneumonia, Ventilator-Associated [DISEASES], infecciones bacterianas y micosis::infección::infección hospitalaria::neumonía asociada al ventilador [ENFERMEDADES], General Immunology and Microbiology, Ecology, Physiology, terapéutica::hipertermia inducida [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Pneumònia, Cell Biology, acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinfecciosos::antibacterianos [COMPUESTOS QUÍMICOS Y DROGAS], Infeccions nosocomials, Infectious Diseases, Genetics, Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Anti-Bacterial Agents [CHEMICALS AND DRUGS], Medicaments antibacterians, Therapeutics::Hyperthermia, Induced [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT]
Abstract

Animal model; Biofilm; Hyperthermia Model animal; Biofilm; Hipertèrmia Modelo animal; Biofilm; Hipertermia There is currently an urgent need to find new strategies to tackle antimicrobial resistance and biofilm-related infections. This study has two aims. First, we evaluated the in vitro efficacy of hyperthermia in preventing biofilm formation on the surfaces of polyvinyl chloride discs. Second, we assessed the in vivo efficacy of hyperthermia in preventing biofilm formation in endotracheal tubes (ETTs) of a rabbit model. For the in vitro studies, nine clinical extensively drug-resistant/multidrug-resistant Gram-negative isolates of Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa and three clinical methicillin-resistant Staphylococcus aureus strains were studied. For biofilm formation, an adhesion step of 30 or 90 min followed by a growth step of 24 h were performed with application of one, two, and three pulses at 42°C for 15 min each pulse after the adhesion step. For the in vivo studies, New Zealand rabbits were intubated with ETTs previously colonized with K. pneumoniae or P. aeruginosa strains, and three pulses at 42°C for 15 min were applied after the adhesion step. The application of three pulses at 42°C for 15 min each pulse was needed to achieve the prevention of the in vitro biofilm formation of 100% of the tested strains. The application of heat pulses in a rabbit intubation model led to biofilm prevention of 85% against two K. pneumoniae strains and 80% against two P. aeruginosa strains compared to the control group. Hyperthermia application through pulses at 42°C could be a new nonantibiotic strategy to prevent biofilm formation in ETTs. IMPORTANCE Biofilm-producing microorganisms are considered medically crucial since they cause 80% of the infections that occur in the human body. Medical devices such as endotracheal tubes (ETTs) can act as a reservoir for pathogens providing the surface to which microorganisms can adhere and cause biofilm-associated infections in critically ill patients. This biofilm has been related with the development of ventilator-associated pneumonia (VAP), with an incidence of 8 to 28%, a mortality rate up to 17% and its associated high extra costs. Although some VAP-preventive measures have been reported, they have not demonstrated a significant reduction of VAP incidence. Therefore, we present a new nonantibiotic strategy based on hyperthermia application to prevent biofilm formation inside ETTs. This technology could reduce VAP incidence, intubation duration, hospital and intensive care unit (ICU) length stays, and mortality rates. Consequently, this could decrease the antibiotics administered and influence the impact of antibiotic resistance in the ICU. This study was supported by research grants from the Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III (FIS 01162), la Marató TV3 (472/U/2018), the CaixaImpulse Program (Fundació “LaCaixa”), the Fundación para la Innovación y la Prospectiva en Salud en España (FIPSE 3932-21), and the Spanish Network for the Research in Infectious Diseases (REIPI RD19/0016).

Published
2023
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40. In Vitro and In Vivo Antimicrobial Activity of Hypochlorous Acid against Drug-Resistant and Biofilm-Producing Strains

Author

Marta Palau, Estela Muñoz, Enric Lujan, Nieves Larrosa, Xavier Gomis, Ester Márquez, Oscar Len, Benito Almirante, Jordi Abellà, Sergi Colominas, Joan Gavaldà, Institut Català de la Salut, [Palau M, Len O, Almirante B, Gavaldà J] Laboratori de Resistència Antibiòtica, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Muñoz E] Laboratori de Resistència Antibiòtica, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Lujan E] Electrochemical Methods Laboratory-Analytical and Applied Chemistry Department, IQS School of Engineering, Universitat Ramon Llull, Barcelona, Spain. [Larrosa N] Spanish Network for Research in Infectious Diseases (REIPI RD19/0016), Instituto de Salud Carlos III, Madrid, Spain. CIBERINFEC, ISCIII—CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain. Servei de Microbiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Gomis X] Laboratori de Resistència Antibiòtica, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. CIBERINFEC, ISCIII—CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain. [Márquez E] Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Microbiology (medical), Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents [CHEMICALS AND DRUGS], Microbiological Phenomena::Drug Resistance, Microbial [PHENOMENA AND PROCESSES], infecciones bacterianas y micosis::infección::enfermedades transmisibles [ENFERMEDADES], General Immunology and Microbiology, Ecology, Physiology, Otros calificadores::/uso terapéutico [Otros calificadores], Medicaments antiinfecciosos - Ús terapèutic, acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antiinfecciosos [COMPUESTOS QUÍMICOS Y DROGAS], Cell Biology, Inorganic Chemicals::Acids::Acids, Noncarboxylic::Hypochlorous Acid [CHEMICALS AND DRUGS], compuestos inorgánicos::ácidos::ácidos no carboxílicos::ácido hipocloroso [COMPUESTOS QUÍMICOS Y DROGAS], Infectious Diseases, Àcids carboxílics, Genetics, Bacterial Infections and Mycoses::Infection::Communicable Diseases [DISEASES], Other subheadings::/therapeutic use [Other subheadings], fenómenos microbiológicos::farmacorresistencia microbiana [FENÓMENOS Y PROCESOS], Malalties transmissibles - Tractament, Resistència als medicaments
Abstract

Antibiotic lock technique; Biofilms; Catheter-related infection Técnica de bloqueo antibiótico; Biopelículas; Infección relacionada con el catéter Tècnica de bloqueig antibiòtic; Biofilms; Infecció relacionada amb el catèter The aims of this study were as follows. First, we determined the antimicrobial efficacy of hypochlorous acid (HClO) against bacterial, fungal, and yeast strains growing planktonically and growing in biofilms. Second, we sought to compare the activity of the combination of daptomycin and HClO versus those of the antimicrobial agents alone for the treatment of experimental catheter-related Staphylococcus epidermidis infection (CRI) using the antibiotic lock technique (ALT) in a rabbit model. HClO was generated through direct electric current (DC) shots at determined amperages and times. For planktonic susceptibility studies, 1 to 3 DC shots of 2, 5, and 10 mA from 0 to 300 s were applied. A DC shot of 20 mA from 0 to 20 min was applied to biofilm-producing strains. Central venous catheters were inserted into New Zealand White rabbits, inoculated with an S. epidermidis strain, and treated with saline solution or ALT using daptomycin (50 mg/mL), HClO (20 mA for 45 min), or daptomycin plus HClO. One hundred percent of the planktonic bacterial, fungal, and yeast strains were killed by applying one DC shot of 2, 5, and 10 mA, respectively. One DC shot of 20 mA for 20 min was sufficient to eradicate 100% of the tested biofilm-producing strains. Daptomycin plus HClO lock therapy showed the highest activity for experimental CRI with S. epidermidis. HClO could be an effective strategy for treating infections caused by extensively drug-resistant or multidrug-resistant and biofilm-producing strains in medical devices and chronic wounds. The results of the ALT using daptomycin plus HClO may be promising. IMPORTANCE Currently, drug-resistant infections are increasing and there are fewer antibiotics available to treat them. Therefore, there is an urgent need to find new antibiotics and nonantimicrobial strategies to treat these infections. We present a new nonantibiotic strategy based on hypochlorous acid generation to treat long-term catheter-related and chronic wounds infections. This study was supported by research grants from the Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III (FIS 01162), la Marató TV3 (472/U/2018), and CaixaImpulse Program (Fundació “LaCaixa”) and the Spanish Network for the Research in Infectious Diseases (REIPI RD19/0016).

Published
2022

41. Contribution of efflux pumps, porins, and β-lactamases to multidrug resistance in clinical isolates of Acinetobacter baumannii

Author

Jerónimo Pachón, María Tomás, Germán Bou, Carlos Rumbo, Luis Martínez-Martínez, María M. López, Jesús Rodríguez-Baño, José Miguel Cisneros, C. Ruiz de Alegría, Almudena Jiménez Pascual, Felipe Fernández-Cuenca, Eva Gato, Jordi Vila, Antimicrobials (GEIH-GEMARA) from the Spanish Society of Clinical Microbiology and Infectious Diseases (SEIMC), The Spanish Network for Research in Infectious Diseases (REIPI), [Rumbo,C, Gato,E, López,M, Bou,G, Tomás,M] Department of Microbiology, Complejo Hospitalario Universitario a Coruña-INIBIC, La Coruña, Spain.[Ruiz de Alegría,C, Martínez-Martínez,L] Department of Clinical Microbiology, Hospital Universitario Marqués de Valdecilla-IFIMAV, Santander, Spain.[Fernández-Cuenca,F, Rodríguez-Baño,J, Pascual,A] Clinical Unit of Infectious Diseases and Microbiology, Hospital Universitario Virgen Macarena, Seville, Spain.[Vila,J] Department of Clinical Microbiology, Hospital Clinic-CRESIB, School of Medicine, University of Barcelona, Barcelona, Spain.[Cisneros,JM] Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/CSIC/University of Seville, Seville, Spain., Research in our laboratories is financially supported by grants from the Instituto de Salud Carlos III, the Spanish Network for Research in Infectious Diseases (REIPI RD 06/0008/0025), the Fondo de Investigaciones Sanitarias (PI08/1368 and PS09/00687 to G.B. and PI10/00056 to M.T.), SERGAS (PS07/90), and the Xunta de Galicia (07CSA050916PR). C.R. is funded by a doctoral grant (PFIS) from the Instituto de Salud Carlos III, and M.T. is supported by the Instituto de Salud Carlos III (program Miguel Servet), both from the Ministerio de Economia y Competitividad., and Universidad de Sevilla. Departamento de Medicina

Subjects
Acinetobacter baumannii, Aminoglicósidos, Porinas, Tigecycline, Drug resistance, Quinolones, Carbapenémicos, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Aromatic::Polycyclic Hydrocarbons, Aromatic::Naphthacenes::Tetracyclines [Medical Subject Headings], Drug Resistance, Multiple, Bacterial, polycyclic compounds, Pharmacology (medical), Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Carrier Proteins::Membrane Transport Proteins::ATP-Binding Cassette Transporters [Medical Subject Headings], Phylogeny, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Amidohydrolases::beta-Lactamases [Medical Subject Headings], Minocycline, Anti-Bacterial Agents, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Microbiological Techniques::Microbial Sensitivity Tests [Medical Subject Headings], Phenomena and Processes::Microbiological Phenomena::Bacterial Physiological Phenomena::Drug Resistance, Bacterial::Drug Resistance, Multiple, Bacterial [Medical Subject Headings], Infectious Diseases, Tetracyclines, Gentamicin, Efflux, Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams::Carbapenems [Medical Subject Headings], Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Anti-Bacterial Agents [Medical Subject Headings], medicine.drug, Acinetobacter Infections, beta-Lactamasas, Tetraciclinas, CL 331002, Porins, Microbial Sensitivity Tests, Biology, beta-Lactamases, Microbiology, Diseases::Bacterial Infections and Mycoses::Bacterial Infections::Gram-Negative Bacterial Infections::Moraxellaceae Infections::Acinetobacter Infections [Medical Subject Headings], Organisms::Bacteria::Gram-Negative Bacteria::Gram-Negative Aerobic Bacteria::Gram-Negative Aerobic Rods and Cocci::Moraxellaceae::Acinetobacter::Acinetobacter baumannii [Medical Subject Headings], Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 2-Ring::Quinolines::Quinolones [Medical Subject Headings], Antibiotic resistance, Mechanisms of Resistance, medicine, Humans, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Carrier Proteins::Membrane Transport Proteins::Ion Channels::Porins [Medical Subject Headings], Pharmacology, Chemicals and Drugs::Carbohydrates::Glycosides::Aminoglycosides [Medical Subject Headings], Gene Expression Regulation, Bacterial, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, bacterial infections and mycoses, Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams::Cephalosporins [Medical Subject Headings], Multiple drug resistance, Aminoglycosides, Carbapenems, Quinolonas, Phenomena and Processes::Genetic Phenomena::Phylogeny [Medical Subject Headings], bacteria, ATP-Binding Cassette Transporters
Abstract

We investigated the mechanisms of resistance to carbapenems, aminoglycosides, glycylcyclines, tetracyclines, and quinolones in 90 multiresistant clinical strains of Acinetobacter baumannii isolated from two genetically unrelated A. baumannii clones: clone PFGE-ROC-1 (53 strains producing the OXA-58 β-lactamase enzyme and 18 strains with the OXA-24 β-lactamase) and clone PFGE-HUI-1 (19 strains susceptible to carbapenems). We used real-time reverse transcriptase PCR to correlate antimicrobial resistance (MICs) with expression of genes encoding chromosomal β-lactamases (AmpC and OXA-51), porins (OmpA, CarO, Omp33, Dcap-like, OprB, Omp25, OprC, OprD, and OmpW), and proteins integral to six efflux systems (AdeABC, AdeIJK, AdeFGH, CraA, AbeM, and AmvA). Overexpression of the AdeABC system (level of expression relative to that by A. baumannii ATCC 17978, 30- to 45-fold) was significantly associated with resistance to tigecycline, minocycline, and gentamicin and other biological functions. However, hyperexpression of the AdeIJK efflux pump (level of expression relative to that by A. baumannii ATCC 17978, 8- to 10-fold) was significantly associated only with resistance to tigecycline and minocycline (to which the TetB efflux system also contributed). TetB and TetA(39) efflux pumps were detected in clinical strains and were associated with resistance to tetracyclines and doxycycline. The absence of the AdeABC system and the lack of expression of other mechanisms suggest that tigecycline-resistant strains of the PFGE-HUI-1 clone may be associated with a novel resistance-nodulation-cell efflux pump (decreased MICs in the presence of the inhibitor Phe-Arg β-naphthylamide dihydrochloride) and the TetA(39) system.

Published
2013

42. SARS-CoV-2 viral load in nasopharyngeal swabs is not an independent predictor of unfavorable outcome

Author

Sonsoles Salto-Alejandre, Judith Berastegui-Cabrera, Pedro Camacho-Martínez, Carmen Infante-Domínguez, Marta Carretero-Ledesma, Juan Carlos Crespo-Rivas, Eduardo Márquez, José Manuel Lomas, Claudio Bueno, Rosario Amaya, José Antonio Lepe, José Miguel Cisneros, Jerónimo Pachón, Elisa Cordero, Javier Sánchez-Céspedes, The Virgen del Rocío Hospital COVID-19 Working Team, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Junta de Andalucía, Salto-Alejandre, Sonsoles, Camacho-Martínez, Pedro, Sánchez-Céspedes, Javier, Salto-Alejandre, Sonsoles [0000-0002-1280-4810], Camacho-Martínez, Pedro [0000-0002-6331-4600], Sánchez-Céspedes, Javier [0000-0003-2707-1979], The Virgen del Rocío Hospital COVID-19 Working Team, [Salto-Alejandre,S, Berastegui-Cabrera,J, Camacho-Martínez,P, Infante-Domínguez,C, Carretero-Ledesma,M, Crespo-Rivas,JC, Lomas,JM, Lepe,JA, Cisneros,JM, Cordero,E, Sánchez-Céspedes,J] Unit of Infectious Diseases, Microbiology, and Preventive Medicine, Virgen del Rocío University Hospital, Seville, Spain. [Salto-Alejandre,S, Pachón,J, Sánchez-Céspedes,J] Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain. [Márquez,E] Medico Surgical Unit of Respiratory Diseases, Virgen del Rocío University Hospital, Seville, Spain. [Bueno,C] Unit of Emergencies, Virgen del Rocío University Hospital, Seville, Spain. [Amaya,R] Intensive Care Unit, Virgen del Rocío University Hospital, Seville, Spain. [Pachón,J, Cordero,E] Department of Medicine, University of Seville, Seville, Spain., Tis work was supported by National Plan R+D+I 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministry of Economy, Industry, and Competitiveness, Spanish Network for Research in Infectious Diseases [REIPI RD16/0016/0009], cofnanced by European Develop ment Regional Fund 'A way to achieve Europe', Operative program Intelligent Growth 2014–2020, and supported by Grants from the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Proyectos de Investigación sobre el SARS-CoV-2 y la enfermedad COVID-19 [COV20/00370, and COV20/00580]. J.S.C. is a researcher belong ing to the program 'Nicolás Monardes' (C-0059-2018), Servicio Andaluz de Salud, Junta de Andalucía, Spain.

Subjects
0301 basic medicine, Male, Logistic regression, Severity of Illness Index, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], law.invention, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Patient Admission, Carga Viral, law, Nasopharynx, Clinical endpoint, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Aged, 80 and over, Multidisciplinary, Pronóstico, Middle Aged, Viral Load, Prognosis, Intensive care unit, Death, Intensive Care Units, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Health Surveys::Health Status Indicators::Patient Acuity::Severity of Illness Index [Medical Subject Headings], Muerte, Quartile, COVID-19 Nucleic Acid Testing, RNA, Viral, Medicine, Female, Viral load, Adult, medicine.medical_specialty, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Anatomy::Respiratory System::Pharynx::Nasopharynx [Medical Subject Headings], Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Science, 030106 microbiology, Check Tags::Male [Medical Subject Headings], Real-Time Polymerase Chain Reaction, Health Care::Health Care Facilities, Manpower, and Services::Health Facilities::Hospital Units::Intensive Care Units [Medical Subject Headings], Article, 03 medical and health sciences, Internal medicine, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Follow-Up Studies [Medical Subject Headings], Severity of illness, medicine, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Patient Care::Hospitalization::Patient Admission [Medical Subject Headings], Humans, Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Viral [Medical Subject Headings], Persons::Persons::Age Groups::Adult [Medical Subject Headings], Aged, business.industry, SARS-CoV-2, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Nucleic Acid Amplification Techniques::Polymerase Chain Reaction::Real-Time Polymerase Chain Reaction [Medical Subject Headings], COVID-19, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Diseases::Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [Medical Subject Headings], Check Tags::Female [Medical Subject Headings], Risk factors, Persons::Persons::Age Groups::Adult::Aged::Aged, 80 and over [Medical Subject Headings], Viral infection, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Microbiological Techniques::Viral Load [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis [Medical Subject Headings], business, Follow-Up Studies
Abstract

The aim was to assess the ability of nasopharyngeal SARS-CoV-2 viral load at first patient’s hospital evaluation to predict unfavorable outcomes. We conducted a prospective cohort study including 321 adult patients with confirmed COVID-19 through RT-PCR in nasopharyngeal swabs. Quantitative Synthetic SARS-CoV-2 RNA cycle threshold values were used to calculate the viral load in log10 copies/mL. Disease severity at the end of follow up was categorized into mild, moderate, and severe. Primary endpoint was a composite of intensive care unit (ICU) admission and/or death (n = 85, 26.4%). Univariable and multivariable logistic regression analyses were performed. Nasopharyngeal SARS-CoV-2 viral load over the second quartile (≥ 7.35 log10 copies/mL, p = 0.003) and second tertile (≥ 8.27 log10 copies/mL, p = 0.01) were associated to unfavorable outcome in the unadjusted logistic regression analysis. However, in the final multivariable analysis, viral load was not independently associated with an unfavorable outcome. Five predictors were independently associated with increased odds of ICU admission and/or death: age ≥ 70 years, SpO2, neutrophils > 7.5 × 103/µL, lactate dehydrogenase ≥ 300 U/L, and C-reactive protein ≥ 100 mg/L. In summary, nasopharyngeal SARS-CoV-2 viral load on admission is generally high in patients with COVID-19, regardless of illness severity, but it cannot be used as an independent predictor of unfavorable clinical outcome., This work was supported by National Plan R+D+I 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministry of Economy, Industry, and Competitiveness, Spanish Network for Research in Infectious Diseases [REIPI RD16/0016/0009]; cofinanced by European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 2014–2020; and supported by Grants from the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Proyectos de Investigación sobre el SARS-CoV-2 y la enfermedad COVID-19 [COV20/00370; COV20/00580]. J.S.C. is a researcher belonging to the program “Nicolás Monardes” (C-0059-2018), Servicio Andaluz de Salud, Junta de Andalucía, Spain.

Published
2021

43. Risk Factors for Relapse in Acute Bacterial Prostatitis: the Impact of Antibiotic Regimens

Author

Carles Pigrau, Benito Almirante, Pau Bosch-Nicolau, Judit Serra-Pladevall, Ester Marquez-Algaba, Belén Viñado, Joaquin Burgos, Institut Català de la Salut, [Marquez-Algaba E, Bosch-Nicolau P, Burgos J] Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Pigrau C, Almirante B] Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0003), Seville, Spain. [Viñado B, Serra-Pladevall J] Servei de Microbiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Male, antibiotic resistance, Physiology, Antibiotics, Male Urogenital Diseases::Genital Diseases, Male::Prostatic Diseases::Prostatitis [DISEASES], Quinolones, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Recurrence, Risk Factors, acute bacterial prostatitis, Microorganismes - Resistència als medicaments, enfermedades urogenitales masculinas::enfermedades de los genitales masculinos::enfermedades de la próstata::prostatitis [ENFERMEDADES], relapse, Aged, 80 and over, Ecology, Pyelonephritis, Mortality rate, beta-lactams, Middle Aged, Microbiological Phenomena::Bacterial Physiological Phenomena::Drug Resistance, Bacterial [PHENOMENA AND PROCESSES], QR1-502, Anti-Bacterial Agents, Prostatitis, Ciprofloxacin, Infectious Diseases, Female, Pròstata - Malalties - Tractament, medicine.drug, Research Article, Microbiology (medical), Adult, medicine.medical_specialty, Bacteriuria, medicine.drug_class, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Pròstata - Malalties - Recaiguda, técnicas de investigación::métodos epidemiológicos::estadística como asunto::probabilidad::riesgo::factores de riesgo [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Microbiology, Antibiotic resistance, Internal medicine, Drug Resistance, Bacterial, Trimethoprim, Sulfamethoxazole Drug Combination, Genetics, medicine, Humans, Risk factor, co-trimoxazole, Aged, General Immunology and Microbiology, business.industry, Cell Biology, Odds ratio, medicine.disease, fenómenos microbiológicos::fenómenos fisiológicos bacterianos::farmacorresistencia bacteriana [FENÓMENOS Y PROCESOS], Chronic Disease, Etiology, Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], business
Abstract

Acute bacterial prostatitis; Antibiotic resistance; Relapse Prostatitis bacteriana aguda; Resistencia a los antibióticos; Recaída Prostatitis bacteriana aguda; Resistència als antibiòtics; Recaiguda The aim of the study was to analyze the risk factors for relapse in patients with acute bacterial prostatitis (ABP), focusing on the impact of different antibiotic regimens. We conducted an observational study of all patients diagnosed with ABP (irritative and/or obstructive urinary symptoms, temperature of >37.8°C, and the presence of bacteriuria in urine culture, in the absence of data suggesting pyelonephritis) from January 2017 to December 2018. The main outcome was relapse. We performed a multivariate analysis to identify the risk factors associated with relapse. A propensity score with inverse weighting was applied to attenuate antibiotic selection bias. We included 410 patients. The mean age was 68 years; 28.8% had diabetes mellitus, and 61.1% benign prostatic hyperplasia. The most common isolated bacteria were Escherichia coli (62.4%) and Klebsiella spp. (10%). The overall resistance rate was 39.5% to quinolones. The mortality rate was 1.2%, and the relapse rate was 6.3%. The only independent risk factor for relapse was inadequate antibiotic therapy (odds ratio [OR] 12.3; 95% confidence interval [95% CI], 3.5 to 43.1). When the antibiotic was modified according to the susceptibility pattern, the rates of relapse were 1.8% in those treated with ciprofloxacin, 3.6% with intravenous beta-lactam, 9.3% with co-trimoxazole, and 9.8% with oral (p.o.) beta-lactam (P = 0.03). Treatment with oral beta-lactam (OR, 5.3; 95% CI, 1.2 to 23.3) and co-trimoxazole (OR, 4.9; 95% CI, 1.1 to 23.2) were associated with a risk of relapse. In this large real-life observational study, a significantly higher relapse rate was observed when antibiotic treatment was inadequate. When the antibiotic was tailored, quinolones and intravenous beta-lactams had a lower relapse rate than co-trimoxazole and oral beta-lactams. IMPORTANCE In the manuscript, we report a large series of acute bacterial prostatitis cases and describe data about the etiology, antibiotic resistance rate, and outcome, specially focused on the risk factors for relapse. We found high rates of resistance to the most frequently used antibiotics and a high relapse rate in patients whose treatment was not adjusted according to their microbiological susceptibility. We did not observe differences, though, in mortality or relapse according to appropriate or inappropriate empirical treatment. What is new in this article is the different relapse rates observed depending upon the definitive adequate antibiotic used. Quinolones and intravenous (i.v.) beta-lactam have lower rates of relapse (1.8% and 3.6%, respectively) compared to co-trimoxazole and oral (p.o.) beta-lactam (3.3% and 9.8%, respectively). Clinicians should carefully choose an adequate antibiotic for definitive ABP treatment depending on the results of microbiological isolation, using quinolones as the first option. Whenever quinolones cannot be administered, i.v. beta-lactams seem to be the second-best option. The Spanish Network for Research in Infectious Diseases is supported by AGAUR grant 2017 SGR 1055, Generalitat de Catalunya. No other financial support was received for this work.

Published
2021

44. Impact of an Antimicrobial Stewardship Program on the Incidence of Carbapenem Resistant Gram-Negative Bacilli: An Interrupted Time-Series Analysis

Author

Elena Pérez-Nadales, Julián Torre-Cisneros, José Ramón del Prado, Luis Martínez-Martínez, Lucrecia García-Martinez, Germán Peñalva, Angela Cano, Elena García-Martinez, José Miguel Cisneros, Inmaculada Salcedo, Manuel Recio, Juan José Castón, Teresa López-Viñau, José Rumbao Aguirre, Irene Gracia-Ahufinger, Montserrat Muñoz-Rosa, Carmen de la Fuente, Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), Red Española de Investigación en Patología Infecciosa, European Commission, [López-Viñau,T, García-Martínez,L, Del Prado,JR] Pharmacy Unit, Reina Sofia University Hospital, Cordoba, Spain. [López-Viñau,T, Castón,JJ, Cano,Á, Recio,M, Pérez-Nadales,E, Torre-Cisneros,J] Infectious Diseases Unit, Reina Sofia University Hospital, Maimonides, Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba (UCO), Cordoba, Spain. [Peñalva,G, Cisneros,JM] Department of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville, Virgen del Rocio University Hospital, Seville, Spain. [Muñoz-Rosa,M, Martínez-Martínez,L, Gracia-Ahufinger,I] Microbiology Unit, Reina Sofia University Hospital, IMIBIC, Department of Agricultural Chemistry, Edafology and Microbiology, University of Cordoba, Cordoba, Spain. [Rumbao Aguirre,J, García-Martínez,E] Hospital Management, Reina Sofia University Hospital, Cordoba, Spain. [Salcedo,I] Preventive Medicine Unit, Reina Sofia University Hospital, Cordoba, Spain. [de la Fuente,C] Intensive Care Unit, Reina Sofia University Hospital, Cordoba, Spain., This research was funded by the Plan Nacional de I + D+i 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0008, and RD16/0016/0009) co-financed by European Development Regional Fund ‘A way to achieve Europe’ and Operative program intelligent Growth 2014–2020, which did not participate in the development of the program or the analysis of its results.

Subjects
0301 basic medicine, Carbapenem, Carbapenem-resistant enterobacteriaceae, Antimicrobial resistance, Biochemistry, Carbapenémicos, Interrupted Time Series Analysis, 0302 clinical medicine, Information Science::Information Science::Data Collection::Vital Statistics::Morbidity::Incidence [Medical Subject Headings], Health Care::Environment and Public Health::Public Health [Medical Subject Headings], polycyclic compounds, Medicine, Antimicrobial stewardship, Pharmacology (medical), 030212 general & internal medicine, General Pharmacology, Toxicology and Pharmaceutics, Health Care::Health Care Facilities, Manpower, and Services::Health Facilities::Hospitals [Medical Subject Headings], Incidence (epidemiology), Mortality rate, Carbapenemases, Organisms::Bacteria::Gram-Negative Bacteria::Gram-Negative Facultatively Anaerobic Rods::Enterobacteriaceae::Escherichia::Escherichia coli [Medical Subject Headings], Klebsiella pneumoniae, Infectious Diseases, carbapenem-resistant Enterobacteriaceae, carbapenems, Organisms::Bacteria::Gram-Negative Bacteria::Gram-Negative Facultatively Anaerobic Rods::Enterobacteriaceae::Klebsiella::Klebsiella pneumoniae [Medical Subject Headings], Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents [Medical Subject Headings], Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams::Carbapenems [Medical Subject Headings], Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Anti-Bacterial Agents [Medical Subject Headings], medicine.drug, Microbiology (medical), medicine.medical_specialty, carbapenemases, 030106 microbiology, Farmacorresistencia microbiana, RM1-950, Microbiology, Article, 03 medical and health sciences, Antibiotic resistance, Carbapenem resistant Enterobacteriaceae, Internal medicine, Enterobacterias resistentes a carbapenémicos, Antimicrobial stewardship program, antimicrobial resistance, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Statistics as Topic::Regression Analysis [Medical Subject Headings], Programas de optimización del uso de los antimicrobianos, antimicrobial stewardship program, Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 2-Ring::Quinolines [Medical Subject Headings], business.industry, Gram negative bacilli, biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses, Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams::Cephalosporins [Medical Subject Headings], Carbapenem-resistant Enterobacteriaceae, Carbapenems, Therapeutics. Pharmacology, business
Abstract

This article belongs to the Section Antibiotics Use and Antimicrobial Stewardship., Carbapenem-resistant Gram-negative bacilli (CR-GNB) are a critical public health threat, and carbapenem use contributes to their spread. Antimicrobial stewardship programs (ASPs) have proven successful in reducing antimicrobial use. However, evidence on the impact of carbapenem resistance remains unclear. We evaluated the impact of a multifaceted ASP on carbapenem use and incidence of CR-GNB in a high-endemic hospital. An interrupted time-series analysis was conducted one year before and two years after starting the ASP to assess carbapenem consumption, CR-GNB incidence, death rates of sentinel events, and other variables potentially related to CR-GNB incidence. An intense reduction in carbapenem consumption occurred after starting the intervention and was sustained two years later (relative effect −83.51%; 95% CI −87.23 to −79.79). The incidence density of CR-GNB decreased by −0.915 cases per 1000 occupied bed days (95% CI −1.743 to −0.087). This effect was especially marked in CR-Klebsiella pneumoniae and CR-Escherichia coli, reversing the pre-intervention upward trend and leading to a relative reduction of −91.15% (95% CI −105.53 to −76.76) and −89.93% (95% CI −107.03 to −72.83), respectively, two years after starting the program. Death rates did not change. This ASP contributed to decreasing CR-GNB incidence through a sustained reduction in antibiotic use without increasing mortality rates., This research was funded by the Plan Nacional de I + D+i 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0008; RD16/0016/0009) co-financed by European Development Regional Fund ‘A way to achieve Europe’ and Operative program intelligent Growth 2014–2020, which did not participate in the development of the program or the analysis of its results.

Published
2021
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45. Efficacy of Fosfomycin and Its Combination With Aminoglycosides in an Experimental Sepsis Model by Carbapenemase-Producing Klebsiella pneumoniae Clinical Strains

Author

Tania Cebrero-Cangueiro, Gema Labrador-Herrera, Álvaro Pascual, Caridad Díaz, Jesús Rodríguez-Baño, Jerónimo Pachón, José P. del Palacio, María E. Pachón-Ibáñez, M. Carmen Conejo, [Cebrero-Cangueiro,T, Labrador-Herrera,G, Pachón-Ibáñez,ME] Clinical Unit of Infectious Diseases, Microbiology, and Preventive Medicine, University Hospital Virgen del Rocío, Seville, Spain. [Cebrero-Cangueiro,T, Pascual,Á, Rodríguez-Baño,J, Pachón,J, Pachón-Ibáñez,ME] Institute of Biomedicine of Seville (IBiS), Virgen del Rocío and Virgen Macarena University Hospitals/Consejo Superior de Investigaciones Científicas (CSIC)/University of Seville, Seville, Spain. [Cebrero-Cangueiro,T, Pachón,J] Department of Medicine, University of Seville, Seville, Spain. [Pascual,Á, Rodríguez-Baño,J] Clinical Unit of Infectious Diseases, Microbiology, and Preventive Medicine, Virgen Macarena University Hospital, Seville, Spain. [Pascual,Á, Conejo,MC] Department of Microbiology, University of Seville, Seville, Spain. [Díaz,C, Del Palacio,JP] Fundacion Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, MEDINA Foundation, Granada, Spain., This study was supported by the Consejería de Salud of the Junta de Andalucía (PI-0622-2012) and supported by Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI, RD16/0016/0001, RD16/0016/0009)—co-financed by European Development Regional Fund A way to achieve Europe, Operative program Intelligent Growth 2014-2020. MP-I is a researcher belonging to the program Nicolás Monardes (C1-0038-2019), Servicio Andaluz de Salud, Junta de Andalucía, Spain. TC-C was supported by the V Plan Propio of the University of Seville with a postdoctoral contract as research personnel in training. GL-H has a grant from the Ministerio de Ciencia, Innovación y Universidades, Instituto de Salud Carlos III, cofinanced by the European Development Regional Fund (A Way to Achieve Europe) and by the Spanish Network for Research in Infectious Diseases (Grant REIPI RD16/0016/0009)., Universidad de Sevilla. Departamento de Microbiología, Universidad de Sevilla. Departamento de Medicina, Junta de Andalucía, Ministerio de Economia, Industria y Competitividad (MINECO). España, European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER), Instituto de Salud Carlos III, Ministerio de Economía, Industria y Competitividad (España), Red Española de Investigación en Patología Infecciosa, European Commission, Universidad de Sevilla, and Ministerio de Ciencia, Innovación y Universidades (España)

Subjects
Chemicals and Drugs::Carbohydrates::Glycosides::Aminoglycosides::Gentamicins [Medical Subject Headings], Aminoglicósidos, Klebsiella pneumoniae, Time kill curves, Context (language use), Fosfomycin, Carbapenemase-producing Klebsiella pneumoniae, Microbiology, In vivo, medicine, polycyclic compounds, Organisms::Eukaryota::Animals [Medical Subject Headings], fosfomycin, Diseases::Bacterial Infections and Mycoses::Infection::Sepsis [Medical Subject Headings], aminoglycosides, lcsh:R5-920, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice [Medical Subject Headings], biology, Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Amidohydrolases::beta-Lactamases [Medical Subject Headings], business.industry, Chemicals and Drugs::Carbohydrates::Glycosides::Aminoglycosides::Kanamycin::Amikacin [Medical Subject Headings], Chemicals and Drugs::Carbohydrates::Glycosides::Aminoglycosides [Medical Subject Headings], Diseases::Bacterial Infections and Mycoses::Bacterial Infections::Bacteremia [Medical Subject Headings], Fosfomicina, Chemicals and Drugs::Organic Chemicals::Organophosphorus Compounds::Organophosphonates::Fosfomycin [Medical Subject Headings], Anatomy::Tissues::Lymphoid Tissue::Spleen [Medical Subject Headings], General Medicine, biochemical phenomena, metabolism, and nutrition, medicine.disease, Antimicrobial, biology.organism_classification, bacterial infections and mycoses, time kill curves, in vivo, Aminoglycosides, carbapenemase-producing Klebsiella pneumoniae, Amikacin, Bacteremia, Gentamicin, Organisms::Bacteria::Gram-Negative Bacteria::Gram-Negative Facultatively Anaerobic Rods::Enterobacteriaceae::Klebsiella::Klebsiella pneumoniae [Medical Subject Headings], business, lcsh:Medicine (General), medicine.drug
Abstract

Carbapenemase-producing Klebsiella pneumoniae infections are an increasing global threat with scarce and uncertain treatment options. In this context, combination therapies are often used for these infections. The bactericidal and synergistic activity of fosfomycin plus amikacin and gentamicin was studied trough time–kill assays against four clonally unrelated clinical isolates of carbapenemase-producing K. pneumoniae, VIM-1, VIM-1 plus DHA-1, OXA-48 plus CTXM-15, and KPC-3, respectively. The efficacy of antimicrobials that showed synergistic activity in vitro against all the carbapenemase-producing K. pneumoniae were tested in monotherapy and in combination, in a murine peritoneal sepsis model. In vitro, fosfomycin plus amikacin showed synergistic and bactericidal effect against strains producing VIM-1, VIM-1 plus DHA-1, and OXA-48 plus CTX-M-15. Fosfomycin plus gentamicin had in vitro synergistic activity against the strain producing KPC-3. In vivo, fosfomycin and amikacin and its combination reduced the spleen bacterial concentration compared with controls groups in animals infected by K. pneumoniae producing VIM-1 and OXA-48 plus CTX-M-15. Moreover, amikacin alone and its combination with fosfomycin reduced the bacteremia rate against the VIM-1 producer strain. Contrary to the in vitro results, no in vivo efficacy was found with fosfomycin plus amikacin against the VIM-1 plus DHA-1 producer strain. Finally, fosfomycin plus gentamicin reduced the bacterial concentration in spleen against the KPC-3 producer strain. In conclusion, our results suggest that fosfomycin plus aminoglycosides has a dissimilar efficacy in the treatment of this severe experimental infection, when caused by different carbapenemase-producing K. pneumoniae strains. Fosfomycin plus amikacin or plus gentamycin may be useful to treat infections by OXA-48 plus CTX-M-15 or KPC-3 producer strains, respectively., This study was supported by the Consejería de Salud of the Junta de Andalucía (PI-0622-2012) and supported by Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI, RD16/0016/0001, RD16/0016/0009)—co-financed by European Development Regional Fund A way to achieve Europe, Operative program Intelligent Growth 2014-2020. MP-I is a researcher belonging to the program Nicolás Monardes (C1-0038-2019), Servicio Andaluz de Salud, Junta de Andalucía, Spain. TC-C was supported by the V Plan Propio of the University of Seville with a postdoctoral contract as research personnel in training. GL-H has a grant from the Ministerio de Ciencia, Innovación y Universidades, Instituto de Salud Carlos III, cofinanced by the European Development Regional Fund (A Way to Achieve Europe) and by the Spanish Network for Research in Infectious Diseases (Grant REIPI RD16/0016/0009).

Published
2021

46. Population Pharmacokinetics of Piperacillin in Non-Critically Ill Patients with Bacteremia Caused by Enterobacteriaceae

Author

Adoración Valiente-Mendez, Álvaro Pascual, Mercedes Delgado-Valverde, Jesús Rodríguez-Baño, Manuel Camean, William W. Hope, Vicente Merino-Bohórquez, Fernando Docobo-Pérez, Instituto de Salud Carlos III, Ministerio de Economía, Industria y Competitividad (España), Red Española de Investigación en Patología Infecciosa, European Commission, Universidad de Sevilla. Departamento de Farmacología, Pediatría y Radiología, Universidad de Sevilla. Departamento de Microbiología, Universidad de Sevilla. Departamento de Medicina, [Merino-Bohórquez,V, Cameán,M] Unidad de Gestión de Farmacia Hospitalaria, Hospital Universitario Virgen Macarena, Sevilla, Spain. [Merino-Bohórquez,V] Departamento de Farmacología, Universidad de Sevilla, Sevilla, Spain. [Docobo-Pérez,F, Pascual,Á] Departamento de Microbiología, Universidad de Sevilla, Sevilla, Spain. [Docobo-Pérez,F, Valiente-Méndez,A, Delgado-Valverde,M, Pascual,Á, Rodríguez-Baño,J] Instituto de Biomedicina de Sevilla IBIS, Hospital Universitario Virgen Macarena/CSIC/Universidad de Sevilla, Sevilla, Spain. [Docobo-Pérez,F, Rodríguez-Baño,J] Red Española de Investigación en Patología Infecciosa (REIPI RD16/0016), Instituto de Salud Carlos III, Madrid, Spain. [Valiente-Méndez,A, Rodríguez-Baño,J] Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen Macarena, Sevilla, Spain. [Hope,WW] Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK. [Hope,WW] Royal Liverpool and Broadgreen University Hospital Trust, Liverpool, UK. [Rodríguez-Baño,J] Departamento de Medicina, Universidad de Sevilla, Sevilla, Spain., and This study was funded by Plan Nacional de I+D+i 2013–2016, Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001) and PI10/02021, cofunded by European Development Regional Fund 'A way toachieve Europe', Operative Programme Intelligent Growth 2014–2020.

Subjects
0301 basic medicine, piperacillin–tazobactam, Biochemistry, Gastroenterology, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, neurotoxicity, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Monte Carlo Method [Medical Subject Headings], Medicine, Pharmacology (medical), 030212 general & internal medicine, General Pharmacology, Toxicology and Pharmaceutics, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Techniques, Urological::Kidney Function Tests::Glomerular Filtration Rate [Medical Subject Headings], Diseases::Bacterial Infections and Mycoses::Infection::Sepsis [Medical Subject Headings], Organisms::Bacteria::Gram-Negative Bacteria::Gram-Negative Facultatively Anaerobic Rods::Enterobacteriaceae [Medical Subject Headings], education.field_of_study, Diseases::Male Urogenital Diseases::Urologic Diseases::Kidney Diseases::Renal Insufficiency::Renal Insufficiency, Chronic [Medical Subject Headings], Combinación de piperacilina y tazobactam, nephrotoxicity, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability [Medical Subject Headings], Infectious Diseases, Piperacillin/tazobactam, pharmacokinetics, medicine.drug, Microbiology (medical), medicine.medical_specialty, 030106 microbiology, Population, Renal function, bloodstream infection, Microbiology, Loading dose, Article, Nephrotoxicity, 03 medical and health sciences, Pharmacokinetics, Enterobacteriaceae, Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 2-Ring::Bicyclo Compounds, Heterocyclic::Penicillins::Penicillin G::Ampicillin::Piperacillin [Medical Subject Headings], Sepsis, Internal medicine, education, Síndromes de neurotoxicidad, business.industry, lcsh:RM1-950, renal function, medicine.disease, lcsh:Therapeutics. Pharmacology, Farmacocinética, Pruebas de función renal, business, Kidney disease, Piperacillin
Abstract

This study analyzes the pharmacokinetic variability of piperacillin in non-critically ill patients with Enterobacteriaceae bloodstream infections (EBSI) and explores predicted clinical outcomes and piperacillin-related neurotoxicity under different renal conditions. Hospitalized, non-critically ill patients treated with piperacillin–tazobactam for EBSI were included. Four serum samples per patient were collected and analyzed. A population pharmacokinetic model was developed using the Pmetrics package for R. Monte Carlo simulations of various dosage regimens of 4 g piperacillin, administered q8 h or q12 h by short (0.5 h) or long (4 h) infusion, following the different glomerular filtration rate (GFR) categories used to classify chronic kidney disease (Kidney Disease: Improving Global Outcomes, KDIGO) to determine the probability of target attainment (PTA) using a free drug concentrations above the minimal inhibitory concentration (fT &gt, MIC) of 50% for efficacy and targets for piperacillin-associated neurotoxicity. Twenty-seven patients (102 samples) were included. Extended piperacillin infusions reached a PTA &gt, 90% (50%fT &gt, MIC) within the susceptibility range, although a loading dose did not greatly improve the expected outcome. Long infusions reduced the expected toxicity in patients with severe renal impairment. The study supports the use of extended infusions of piperacillin in non-critically ill patients with EBSI. No benefits of a loading dose were expected in our population. Finally, extended infusions may reduce the risk of toxicity in patients with severe renal impairment.

Published
2021

47. Repurposing of the Tamoxifen Metabolites to Combat Infections by Multidrug-Resistant Gram-Negative Bacilli

Author

Jerónimo Pachón, Manuel E. Jiménez-Mejías, Andrea Miró-Canturri, Andrea Vila-Domínguez, Rafael Ayerbe-Algaba, Younes Smani, Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), Red Española de Investigación en Patología Infecciosa, European Commission, Ministerio de Economía y Competitividad (España), Universidad de Sevilla. Departamento de Medicina, Instituto de Biomedicina de Sevilla (IBIS). Grupo de Investigación: CTS-203 Estudio de las Enfermedades Infecciosas, [Miró-Canturri,A, Ayerbe-Algaba,R, Vila-Domínguez,A, Jiménez-Mejías,ME, Smani,Y] Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, University Hospital Virgen del Rocío, Seville, Spain. [Miró-Canturri,A, Pachón,J, Smani,Y] Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío, CSIC, University of Seville, Seville, Spain. [Pachón,J] Department of Medicine, University of Seville, Seville, Spain., and This study was supported by the Instituto de Salud Carlos III, Proyectos de Investigación en Salud (grants PI16/01378 and PI19/01453) and by Plan Nacional de I+D+i 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009)—co-financed by European Development Regional Fund 'A way to achieve Europe', Operative program Intelligent Growth 2014–2020. Younes Smani is supported by the Subprograma Miguel Servet Tipo I from the Ministerio de Economía y Competitividad of Spain (CP15/00132).

Subjects
0301 basic medicine, Terapéutica, medicine.disease_cause, Biochemistry, Organisms::Eukaryota::Animals [Medical Subject Headings], Pharmacology (medical), Tamoxifeno, General Pharmacology, Toxicology and Pharmaceutics, bacteria, Diseases::Bacterial Infections and Mycoses::Infection::Sepsis [Medical Subject Headings], biology, tamoxifen, treatment, Antimicrobial, Tamoxifen metabolite, Acinetobacter baumannii, Organisms::Bacteria::Gram-Negative Bacteria::Gram-Negative Facultatively Anaerobic Rods::Enterobacteriaceae::Escherichia::Escherichia coli [Medical Subject Headings], Infectious Diseases, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Clinical Laboratory Techniques::Microbiological Techniques::Microbial Sensitivity Tests [Medical Subject Headings], Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents [Medical Subject Headings], Bacterias, Infection, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Drug Discovery::Drug Repositioning [Medical Subject Headings], medicine.drug, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Anti-Bacterial Agents [Medical Subject Headings], Microbiology (medical), Membrane permeability, 030106 microbiology, tamoxifen metabolite, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins [Medical Subject Headings], Microbiology, Article, 03 medical and health sciences, Minimum inhibitory concentration, Organisms::Bacteria::Gram-Negative Bacteria::Gram-Negative Aerobic Bacteria::Gram-Negative Aerobic Rods and Cocci::Moraxellaceae::Acinetobacter::Acinetobacter baumannii [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Clinical Laboratory Techniques::Microbiological Techniques::Bacteriological Techniques::Bacterial Load [Medical Subject Headings], Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Aromatic::Benzene Derivatives::Benzylidene Compounds::Stilbenes::Tamoxifen [Medical Subject Headings], medicine, Infección, Escherichia coli, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice [Medical Subject Headings], Bacteria, Pseudomonas aeruginosa, lcsh:RM1-950, Organisms::Bacteria::Gram-Negative Bacteria::Gram-Negative Aerobic Bacteria::Gram-Negative Aerobic Rods and Cocci::Pseudomonadaceae::Pseudomonas::Pseudomonas aeruginosa [Medical Subject Headings], Anatomy::Hemic and Immune Systems::Immune System [Medical Subject Headings], biology.organism_classification, Phenomena and Processes::Chemical Phenomena::Permeability [Medical Subject Headings], infection, Multiple drug resistance, Treatment, Tamoxifen, lcsh:Therapeutics. Pharmacology, 030104 developmental biology
Abstract

This article belongs to the Special Issue The Quest for Novel Antimicrobials: From Chemical Synthesis and Discovery to Mechanisms of Action and Resistance., The development of new strategic antimicrobial therapeutic approaches, such as drug repurposing, has become an urgent need. Previously, we reported that tamoxifen presents therapeutic efficacy against multidrug-resistant (MDR) Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli in experimental infection models by modulating innate immune system cell traffic. The main objective of this study was to analyze the activity of N-desmethyltamoxifen, 4-hydroxytamoxifen, and endoxifen, three major metabolites of tamoxifen, against these pathogens. We showed that immunosuppressed mice infected with A. baumannii, P. aeruginosa, or E. coli in peritoneal sepsis models and treated with tamoxifen at 80 mg/kg/d for three days still reduced the bacterial load in tissues and blood. Moreover, it increased mice survival to 66.7% (for A. baumannii and E. coli) and 16.7% (for P. aeruginosa) when compared with immunocompetent mice. Further, susceptibility and time-kill assays showed that N-desmethyltamoxifen, 4-hydroxytamoxifen, and endoxifen exhibited minimum inhibitory concentration of the 90% of the isolates (MIC90) values of 16 mg/L, and were bactericidal against clinical isolates of A. baumannii and E. coli. This antimicrobial activity of tamoxifen metabolites paralleled an increased membrane permeability of A. baumannii and E. coli without affecting their outer membrane proteins profiles. Together, these data showed that tamoxifen metabolites presented antibacterial activity against MDR A. baumannii and E. coli, and may be a potential alternative for the treatment of infections caused by these two pathogens., This study was supported by the Instituto de Salud Carlos III, Proyectos de Investigación en Salud (grants PI16/01378 and PI19/01453) and by Plan Nacional de I+D+i 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009)—co-financed by European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 2014–2020. Younes Smani is supported by the Subprograma Miguel Servet Tipo I from the Ministerio de Economía y Competitividad of Spain (CP15/00132).

Published
2021
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48. Antimicrobial resistance research in a post-pandemic world: Insights on antimicrobial resistance research in the COVID-19 pandemic

Author

Margo Warren, Birgitta Henriques-Normark, Ramanan Laxminarayan, Ghada Zoubiane, Gian Maria Rossolini, Till T. Bachmann, Adam P. Roberts, Alison Holmes, Sabiha Y. Essack, Benedikt Huttner, Steven J. Hoffman, Charu Kaushic, Herman Goossens, Norio Ohmagari, Srinivas Murthy, Evelina Tacconelli, Jesús Rodríguez-Baño, Shawon Lahiri, Laura Plant, Patriq Fagerstedt, Rafael Cantón, Cornelius J. Clancy, Constance Schultsz, [Rodríguez-Baño,J] Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen Macarena, Seville, Spain. [Rodríguez-Baño,J] Departamento de Medicina, Universidad de Sevilla, Seville, Spain. [Rodríguez-Baño,J] Instituto de Biomedicina de Sevilla (IBiS), Seville, Spain. [Rossolini,GM] Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy. [Rossolini,GM] Clinical Microbiology and Virology Unit, Florence Careggi University Hospital, Florence, Italy. [Schultsz,C] Department of Global Health–AIGHD Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands. [Tacconelli,E] Division of Infectious Diseases, Department of Diagnostic and Public Health, University of Verona, Verona, Italy. [Murthy,S] BC Children’s Hospital, University of British Columbia, Vancouver, Canada. [Ohmagari,N] Disease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo, Japan. [Holmes,A] Department of Medicine, Faculty of Medicine, Imperial College London, London, UK. [Bachmann,T] The University of Edinburgh, Edinburgh Medical School, Division of Infection and Pathway Medicine, The Chancellor’s Building, Edinburgh, UK. [Goossens,H] Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, University of Antwerp, Antwerp, Belgium. [Canton,R] Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria, Madrid, Spain. [Canton,R] Red Española de Investigación en Patología Infecciosa (REIPI), Instituto de Salud Carlos III, Madrid, Spain. [Roberts,AP] Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, UK. [Henriques-Normark,B] Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden. [Henriques-Normark,B] Clinical Microbiology, Karolinska University Hospital, Stockholm, Sweden. [Clancy,CJ] University of Pittsburgh, Pittsburgh, PA, USA. [Huttner,B] Division of Infectious Diseases, Geneva University Hospitals, Faculty of Medicine, University of Geneva, Geneva, Switzerland. [Fagerstedt,P, Lahiri,S] JPIAMR Secretariat, Swedish Research Council, Stockholm, Sweden. [Kaushic,C, Plant,L] Institute of Infection and Immunity, Canadian Institutes of Health Research, Canada. [Kaushic,C] McMaster Immunology Research Center, Department Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada. [Hoffman,SJ] Global Strategy Lab, Dahdaleh Institute for Global Health Research, School of Global Health and Osgoode Hall Law School, York University, Toronto, Canada. [Warren,M] Access to Medicine Foundation, Amsterdam, The Netherlands. [Zoubiane,G, Essack,S] International Centre for Antimicrobial Resistance Solutions (ICARS), Copenhagen, Denmark. [Essack,S] Antimicrobial Research Unit, University of KwaZulu-Natal, Durban, South Africa. [Laxminarayan,R] Center for Disease Dynamics, Economics & Policy, New Delhi, India. [Rodríguez-Baño,J] Red Española de Investigación en Patología Infecciosa (REIPI), Instituto de Salud Carlos III. Madrid, Spain., APR would like to acknowledge funding from the AMR CrossCouncil Initiative through a grant from the Medical Research Council, a Council of UK Research and Innovation [grant number MR/S004793/1], the National Institute for Health Research [grant number NIHR200632] and the Joint Programming Initiative for Antimicrobial Resistance (JPIAMR) via the Medical Research Council in the UK [grant number MR/S037640/1]. JRB and RC acknowledge funding on AMR from Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases [REIPI RD16/0016/0001 and RD16/0016/ 0011], co-financed by the European Regional Development Fund ‘A way to achieve Europe’, Operative Program Intelligence Growth 2014–2020. JRB also acknowledges the Joint Programming Initiative for Antimicrobial Resistance (JPIAMR) via Instituto de Salud Carlos III [grant number AC16/00076]. ET acknowledges funding on AMR from the Joint Programming Initiative for Antimicrobial Resistance (JPIAMR) via the German Federal Ministry of Education and Research (BMBF) [grant number 01KI1830], Innovative Medicines Initiative 1 and 2 Joint Undertaking [grants number 115737,115523 and820755] and the Global Antibiotic Research and Development Partnership (GARDP). LP, PF and SL would like to acknowledge funding to the JPIAMR from the European Commission (EXEDRA, JPI-EC-AMR and JPIAMR-ACTION)., Medical Research Council (UK), UK Research and Innovation, National Institute for Health Research (UK), Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), Red Española de Investigación en Patología Infecciosa, European Commission, Federal Ministry of Education and Research (Germany), Innovative Medicines Initiative, Global Health, AII - Infectious diseases, and APH - Global Health

Subjects
0301 basic medicine, Vulnerability, Antimicrobial stewardship, Antimicrobial resistance, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Pandemic, wc_505, Immunology and Allergy, Phenomena and Processes::Microbiological Phenomena::Bacterial Physiological Phenomena::Drug Resistance, Bacterial [Medical Subject Headings], 030212 general & internal medicine, wb_330, Surveillance, Transmission (medicine), Pharmacology. Therapy, QR1-502, Anti-Bacterial Agents, Investigación, qw_160, Healthcare system, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Anti-Bacterial Agents [Medical Subject Headings], Microbiology (medical), medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Infecciones por coronavirus, 030106 microbiology, Immunology, Microbiology, Article, qw_45, Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Data Collection::Health Surveys::Population Surveillance::Public Health Surveillance [Medical Subject Headings], 03 medical and health sciences, Antibiotic resistance, Stewardship, covid-19, research, surveillance, Drug Resistance, Bacterial, medicine, Humans, Intensive care medicine, Pandemics, Programas de optimización del uso de los antimicrobianos, Pandemia, business.industry, SARS-CoV-2, Research, COVID-19, Health Care::Environment and Public Health::Public Health::Disease Outbreaks::Epidemics::Pandemics [Medical Subject Headings], Diseases::Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [Medical Subject Headings], Infectious disease (medical specialty), wc_518, Clinical Microbiology and Infection, Human medicine, Disciplines and Occupations::Health Occupations::Medicine::Public Health::Epidemiology [Medical Subject Headings], business
Abstract

Antimicrobial resistance must be recognised as a global societal priority - even in the face of the worldwide challenge of the COVID-19 pandemic. COVID-19 has illustrated the vulnerability of our healthcare systems in co-managing multiple infectious disease threats as resources for monitoring and detecting, and conducting research on antimicrobial resistance have been compromised during the pandemic. The increased awareness of the importance of infectious diseases, clinical microbiology and infection control and lessons learnt during the COVID-19 pandemic should be exploited to ensure that emergence of future infectious disease threats, including those related to AMR, are minimised. Harnessing the public understanding of the relevance of infectious diseases towards the long-term pandemic of AMR could have major implications for promoting good practices about the control of AMR transmission., APR would like to acknowledge funding from the AMR Cross-Council Initiative through a grant from the Medical Research Council, a Council of UK Research and Innovation [grant number MR/S004793/1], the National Institute for Health Research [grant number NIHR200632] and the Joint Programming Initiative for Antimicrobial Resistance (JPIAMR) via the Medical Research Council in the UK [grant number MR/S037640/1]. JRB and RC acknowledge funding on AMR from Plan Nacional de I+D+i 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases [REIPI RD16/0016/0001 and RD16/0016/0011], co-financed by the European Regional Development Fund ‘A way to achieve Europe’, Operative Program Intelligence Growth 2014–2020. JRB also acknowledges the Joint Programming Initiative for Antimicrobial Resistance (JPIAMR) via Instituto de Salud Carlos III [grant number AC16/00076]. ET acknowledges funding on AMR from the Joint Programming Initiative for Antimicrobial Resistance (JPIAMR) via the German Federal Ministry of Education and Research (BMBF) [grant number 01KI1830], Innovative Medicines Initiative 1 and 2 Joint Undertaking [grants number 115737, 115523 and820755] and the Global Antibiotic Research and Development Partnership (GARDP). LP, PF and SL would like to acknowledge funding to the JPIAMR from the European Commission (EXEDRA, JPI-EC-AMR and JPIAMR-ACTION).

Published
2021
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49. AOA-2 Derivatives as Outer Membrane Protein A Inhibitors for Treatment of Gram-Negative Bacilli Infections

Author

Rafael Ayerbe-Algaba, Nuria Bayó, Ester Verdú, Raquel Parra-Millán, Jesús Seco, Meritxell Teixidó, Jerónimo Pachón, Ernest Giralt, Younes Smani, Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), Red Española de Investigación en Patología Infecciosa, European Commission, Ministerio de Economía y Competitividad (España), [Ayerbe-Algaba,R, Parra-Millán,R, Smani,Y] Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, University Hospital Virgen del Rocío, Seville, Spain. [Ayerbe-Algaba,R, Pachón,J, Smani,Y] Institute of Biomedicine of Seville (IBiS), University Hospital Virgen del Rocío/Spanish National Research Council (CSIC)/University of Seville, Seville, Spain. [Bayó,N, Verdú,E, Seco,J, Teixidó,M, Giralt,E] Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute for Science and Technology (BIST), Barcelona, Spain. [Pachón,J] Department of Medicine, University of Seville, Seville, Spain. [Giralt,E] Department of Inorganic and Organic Chemistry, University of Barcelona, Barcelona, Spain., This study was supported by the Instituto de Salud Carlos III, Proyectos de Investigación en Salud (Grants PI15/01358, PI16/01378, and PI19/01453) and by Plan Nacional de I + D + i 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Inno-vación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009)—co-financed by the European Development Regional Fund 'A way to achieve Europe,' Operative program Intelligent Growth 2014–2020. YS was supported by the Subprograma Miguel Servet Tipo I from the Ministerio de Economía y Competitividad of Spain (CP15/00132)., and Universidad de Sevilla. Departamento de Medicina

Subjects
Microbiology (medical), Chemicals and Drugs::Organic Chemicals::Amines::Hydroxylamines::Aminooxyacetic Acid [Medical Subject Headings], Bacilli, Proteínas de la membrana bacteriana externa, Inhibitor, Gram-negative bacilli, Proteína estafilocócica A, lcsh:QR1-502, Organisms::Bacteria::Proteobacteria::Gammaproteobacteria::Enterobacteriaceae::Escherichia::Escherichia coli [Medical Subject Headings], AOA-2 derivatives, medicine.disease_cause, Microbiology, lcsh:Microbiology, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 03 medical and health sciences, Organisms::Bacteria::Gram-Negative Bacteria::Gram-Negative Aerobic Bacteria::Gram-Negative Aerobic Rods and Cocci::Moraxellaceae::Acinetobacter::Acinetobacter baumannii [Medical Subject Headings], medicine, Outer membrane protein A, Escherichia coli, Diseases::Bacterial Infections and Mycoses::Infection::Sepsis [Medical Subject Headings], Original Research, 030304 developmental biology, A549 cell, 0303 health sciences, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice [Medical Subject Headings], Infecciones, biology, Infecciones por bacterias gramnegativas, 030306 microbiology, Pseudomonas aeruginosa, Chemistry, In vitro toxicology, Organisms::Bacteria::Gram-Negative Bacteria::Gram-Negative Aerobic Bacteria::Gram-Negative Aerobic Rods and Cocci::Pseudomonadaceae::Pseudomonas::Pseudomonas aeruginosa [Medical Subject Headings], Péptidos, Chemicals and Drugs::Inorganic Chemicals::Bromine Compounds::Hydrobromic Acid::Bromides [Medical Subject Headings], Anatomy::Respiratory System::Lung [Medical Subject Headings], biology.organism_classification, In vitro, outer membrane protein A, Acinetobacter baumannii, inhibitor, Ácido aminooxiacético, Colistin, peptides, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Peptides, Cyclic::Polymyxins::Colistin [Medical Subject Headings], Peptides, medicine.drug
Abstract

Previously, we identified that a cyclic hexapeptide AOA-2 inhibited the interaction of Gram-negative bacilli (GNB) like Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli to host cells thereby preventing the development of infection in vitro and in a murine sepsis peritoneal model. In this work, we aimed to evaluate in vitro a library of AOA-2 derivatives in order to improve the effect of AOA-2 against GNB infections. Ten AOA-2 derivatives were synthetized for the in vitro assays. Their toxicities to human lung epithelial cells (A549 cells) for 24 h were evaluated by determining the A549 cells viability using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The effect of these peptide derivatives and AOA-2 at 250, 125, 62.5, and 31.25 μg/mL on the attachment of A. baumannii ATCC 17978, P. aeruginosa PAO1 and E. coli ATCC 25922 strains to A549 cells was characterized by adherence and viability assays. None of the 10 derivatives showed toxicity to A549 cells. RW01 and RW06 have reduced more the adherence of ATCC 17978, PAO1 and ATCC 2599 strains to A549 cells when compared with the original compound AOA-2. Moreover, both peptides have increased slightly the viability of infected A549 cells by PAO1 and ATCC 25922 than those observed with AOA-2. Finally, RW01 and RW06 have potentiated the activity of colistin against ATCC 17978 strain in the same level with AOA-2. The optimization program of AOA-2 has generated two derivatives (RW01 and RW06) with best effect against interaction of GNB with host cells, specifically against P. aeruginosa and E. coli., This study was supported by the Instituto de Salud Carlos III, Proyectos de Investigación en Salud (Grants PI15/01358 and PI16/01378) and by Plan Nacional de I + D + i 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Inno-vación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009)—co-financed by the European Development Regional Fund “A way to achieve Europe,” Operative program Intelligent Growth 2014–2020. YS was supported by the Subprograma Miguel Servet Tipo I from the Ministerio de Economía y Competitividad of Spain (CP15/00132).

Published
2021
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50. Impact of Treating Asymptomatic Bacteriuria in Kidney Transplant Recipients: A Prospective Cohort Study

Author

Guillermo Martín-Gutiérrez, Marta Suñer-Poblet, Alejandro Suárez-Benjumea, Carmen González-Corvillo, Jerónimo Pachón, Carmen Infante-Domínguez, Sara Fontserè, Gabriel Bernal, María Eugenia Pachón-Ibáñez, Elisa Cordero, Universidad de Sevilla. Departamento de Medicina, [Fontserè,S, Infante-Domínguez,C, Martín-Gutiérrez,G, Bernal,G, Pachón,J, Pachón-Ibáñez,ME, Cordero,E] Unit of Infectious Diseases, Microbiology, and Preventive Medicine, Virgen del Rocío University Hospital of Seville, Seville, Spain. [Suárez-Benjumea,A, Suñer-Poblet,M, González-Corvillo,C] Urology and Nephrology Unit, Virgen del Rocío University Hospital, Seville, Spain. [Pachón,J, Cordero,E] Department of Medicine, University of Seville, Seville, Spain. [Pachón-Ibáñez,ME, Cordero,E] Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital/CSIC/University of Seville, Seville, Spain., and This work was supported by the Instituto de Salud Carlos III, Subdirección General de Evaluación y Fomento de la Investigación, Ministerio de Economía, Industria y Competitividad (PI17-01405) and by Plan Nacional de I + D + i 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009)-cofinanced by European Development Regional Fund 'A way to achieve Europe', Operative program Intelligent Growth 2014–2020. G.M.-G. was supported by a Río Hortega research contract from the Instituto de Salud Carlos III.). M.E.P.I. is supported by the 'Contract to Access to the Spanish System of Research and Innovation, V Research Program of the University of Seville' (USE13901-D) grant.

Subjects
Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Renal Replacement Therapy::Kidney Transplantation [Medical Subject Headings], 030230 surgery, medicine.disease_cause, Biochemistry, Infecciones asintomáticas, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Cystitis, Trasplante de riñón, Pharmacology (medical), 030212 general & internal medicine, Infecciones urinarias, Cistitis, General Pharmacology, Toxicology and Pharmaceutics, Prospective cohort study, Kidney transplantation, Kidney recipients, Diseases::Bacterial Infections and Mycoses::Infection::Urinary Tract Infections::Bacteriuria [Medical Subject Headings], Estudio observacional, Antimicrobial, Infectious Diseases, Organisms::Bacteria::Gram-Negative Bacteria::Gram-Negative Facultatively Anaerobic Rods::Enterobacteriaceae::Klebsiella::Klebsiella pneumoniae [Medical Subject Headings], Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents [Medical Subject Headings], Microbiology (medical), medicine.medical_specialty, prospective observational cohort, kidney recipients, Urinary system, Estudios de cohortes, Microbiology, Article, Diseases::Bacterial Infections and Mycoses::Infection::Urinary Tract Infections [Medical Subject Headings], 03 medical and health sciences, Internal medicine, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Follow-Up Studies [Medical Subject Headings], medicine, cystitis, Thymoglobulin, Pseudomonas aeruginosa, business.industry, lcsh:RM1-950, Organisms::Bacteria::Gram-Negative Bacteria::Gram-Negative Aerobic Bacteria::Gram-Negative Aerobic Rods and Cocci::Pseudomonadaceae::Pseudomonas::Pseudomonas aeruginosa [Medical Subject Headings], Prospective observational cohort, Receptores de trasplantes, asymptomatic bacteriuria, medicine.disease, Urinary tract infections, Transplantation, lcsh:Therapeutics. Pharmacology, Organisms::Bacteria::Gram-Positive Bacteria::Lactobacillales::Enterococcaceae::Enterococcus::Enterococcus faecalis [Medical Subject Headings], Etiology, Diseases::Male Urogenital Diseases::Urologic Diseases::Kidney Diseases::Nephritis::Nephritis, Interstitial::Pyelonephritis [Medical Subject Headings], urinary tract infections, business, Diseases::Male Urogenital Diseases::Urologic Diseases::Urinary Bladder Diseases::Cystitis [Medical Subject Headings], Asymptomatic bacteriuria
Abstract

This study aims to define the epidemiologic, clinical, and microbiological features of asymptomatic bacteriuria (AB) and cystitis in kidney transplantation recipients (KTRs), and to determine the impact of antimicrobial therapy of AB and the risk factors of cystitis. We conducted a prospective observational study of AB and cystitis in KTRs from January to June 2017. One-hundred ninety seven KTRs were included: 175 (88.8%) with AB and 22 (11.2%) with cystitis. The most frequent etiologies were Escherichia coli, Klebsiellapneumoniae, Enterococcusfaecalis, and Pseudomonas aeruginosa. No differences were observed regarding the etiologies, antimicrobial susceptibility patterns, and microbiologic outcomes in AB vs. cystitis. The treatment of AB diminished the microbiological cure and increased the rates of microbiologic relapses and reinfections, in addition, treated AB patients showed a trend of developing symptomatic urinary tract infection in the following six months. The analysis of the data identified the following independent risk factors for cystitis during the six months of follow-up: AB treatment, thymoglobulin induction, previous acute pyelonephritis, and time since transplantation &lt, 1 year. In summary, considering the lack of clinical benefits of treating AB and its impact on cystitis development in the follow-up, we support the recommendation of not screening for or treating AB.

Published
2021

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