25 results on '"Mercedes Delgado-Valverde"'
Search Results
2. Imipenem-Relebactam Susceptibility in Enterobacterales Isolates Recovered from ICU Patients from Spain and Portugal (SUPERIOR and STEP Studies)
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Marta Hernández-García, María García-Castillo, Germán Bou, Emilia Cercenado, Mercedes Delgado-Valverde, Antonio Oliver, Cristina Pitart, Jesús Rodríguez-Lozano, Nuria Tormo, José Melo-Cristino, Margarida F. Pinto, Elsa Gonçalves, Valquíria Alves, Ana Raquel Vieira, Elmano Ramalheira, Luísa Sancho, José Diogo, Rui Ferreira, Hugo Cruz, Catarina Chaves, Joana Duarte, Leonor Pássaro, Jazmín Díaz-Regañón, and Rafael Cantón
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imipenem-relebactam susceptibility ,carbapenemase-producing Enterobacterales ,ICU patients ,Spain ,Portugal ,Microbiology ,QR1-502 - Abstract
ABSTRACT Imipenem-relebactam is a novel β-lactam-β-lactamase inhibitor combination. We evaluated the in vitro activity of imipenem-relebactam and comparators against Enterobacterales clinical isolates recovered in 8 Spanish and 11 Portuguese intensive care units (ICUs) (SUPERIOR, 2016–2017; STEP, 2017–2018). Overall, 747 Enterobacterales isolates (378 Escherichia coli, 252 Klebsiella spp., 64 Enterobacter spp., and 53 other species) were prospectively collected from ICU patients with complicated intraabdominal (cIAI), complicated urinary tract (cUTI), and lower respiratory tract (LRTI) infections. MICs were determined (ISO-broth microdilution), and whole-genome sequencing (WGS) was performed in a subset of isolates displaying susceptible and resistant imipenem-relebactam MICs. Imipenem-relebactam (98.7% susceptible) showed similar activity to ceftazidime-avibactam (99.5% susceptible) and higher than ceftolozane-tazobactam (86.9% susceptible). Imipenem-relebactam was inactive against 1.3% (10/747) isolates, all of them due to carbapenemase production (9 K. pneumoniae and 1 E. cloacae). Imipenem-relebactam was active against 100% of extended-spectrum β-lactamase (ESBL)-E. coli and ESBL-Klebsiella spp. isolates and 80.4% of carbapenemase-Klebsiella spp. producers. Carbapenemase genes were confirmed by WGS in 41 Klebsiella spp.: OXA-48 (20/41), KPC-3 (14/41), OXA-181 (4/41), NDM-1 (1/41), OXA-48 + VIM-2 (1/41), and KPC-3 + VIM-2 (1/41). In Klebsiella spp. isolates, relebactam restored imipenem susceptibility in all KPC-3 producers, and resistant isolates (7/41) were mostly OXA-48 + CTX-M-15-K. pneumoniae high-risk clones (7/9). Intercountry differences were detected as follows: OXA-48 (17/21) was dominant in Spain, unlike KPC-3 (14/15) in Portugal. Imipenem-relebactam was 100% active against CTX-M-15-ST131-H30Rx-E. coli high-risk clone, predominant in both countries. Our results depict the potential role of imipenem-relebactam in ICU patients with cIAIs, cUTIs, and LRTIs due to wild-type ESBL- and carbapenemase-producing Enterobacterales, particularly KPC producers. IMPORTANCE We comparatively evaluate the in vitro activity of a drug combination consisting of a carbapenem (imipenem) and a novel inhibitor of beta-lactamases (relebactam), a mechanism that destroys beta-lactam antibiotics. We assess the activity against a collection of Enterobacterales clinical isolates recovered from difficult-to-treat infections in patients admitted to different intensive care units in Portugal and Spain. Imipenem-relebactam shows excellent activity in avoiding common resistance mechanisms in this setting, such as extended-spectrum beta-lactamases and carbapenemases widely distributed, including KPCs. We show few resistant isolates (
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- 2022
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3. CARB-ES-19 Multicenter Study of Carbapenemase-Producing Klebsiella pneumoniae and Escherichia coli From All Spanish Provinces Reveals Interregional Spread of High-Risk Clones Such as ST307/OXA-48 and ST512/KPC-3
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Javier E. Cañada-García, Zaira Moure, Pedro J. Sola-Campoy, Mercedes Delgado-Valverde, María E. Cano, Desirèe Gijón, Mónica González, Irene Gracia-Ahufinger, Nieves Larrosa, Xavier Mulet, Cristina Pitart, Alba Rivera, Germán Bou, Jorge Calvo, Rafael Cantón, Juan José González-López, Luis Martínez-Martínez, Ferran Navarro, Antonio Oliver, Zaira R. Palacios-Baena, Álvaro Pascual, Guillermo Ruiz-Carrascoso, Jordi Vila, Belén Aracil, María Pérez-Vázquez, Jesús Oteo-Iglesias, the GEMARA/GEIRAS-SEIMC/REIPI CARB-ES-19 Study Group, Mariela Martínez Ramírez, Pilar Zamarrón, Miriam Albert Hernández, M. Pilar Ortega Lafont, Emilia Cercenado, Cristobal del Rosario and Jose Luis Perez Arellano, María Lecuona, Luis López-Urrutia Lorente, José Leiva and José Luis del Pozo, Salvador Giner and Juan Frasquet, Lidia Garcia Agudo and Soledad Illescas, Pedro de la Iglesia, Rosario Sánchez Benito, Eugenio Garduño, Ma Isabel Fernández Natal and Marta Arias, Marta Lamata Subero, Mar Olga Pérez Moreno, Ana Isabel López-Calleja, Luis Torres Sopena, José Manuel Azcona, Alba Belles, Mercè García González, Miriam Valverde Troya and Begoña Palop, Fernando García Garrote, Jose Luis Barrios Andrés, Leyre López Soria, Adelina Gimeno, Susana Sabater, Ester Clapés Sanchez, Jennifer Villa, Nuria Iglesias Nuñez, Rafael Sánchez Arroyo, Inmaculada García García, Susana Hernando, Cristina Seral, Javier Castillo, Eva Riquelme Bravo, Caridad Sainz de Baranda, Oscar Esparcia Rodríguez, Jorge Gaitán, María Huertas, M.a José Rodríguez Escudero, Carmen Aldea, Nerea Sanchez, Antonio Casabella Pernas, Ma Dolores Quesada, Maria Pilar Chocarro, Francisco Javier Ramos, Carmina Martí Sala, Laura Mora, Encarnación Clavijo, Natalia Chueca, Federico García, José Gutierrez Fernández, Juan Manuel Sánchez Hospital de Jérez, Fátima Galán Sánchez, Carmen Liébana, Carolina Roldán, Ma Isabel Cabeza, José María Saavedra, Ma Teresa Cabezas Fernández, Lucía Martínez Lamas, Sonia Rey Cao, Ma Isabel Paz Vidal, Raquel Elisa Rodríguez Tarazona, Amparo Coira Nieto, Ma Luisa Pérez del Molino Bernal, María Gomáriz Díaz, Matxalen Vidal-García, Jose Luis Díaz de Tuesta, Moises García Bravo, Almudena Tinajas, Andrés Canut Blasco, Ma Luz Albina Cordón Rodriguez, Nieves Gonzalo Jiménez, Genoveva Yagüe Guirao, Fe Tubau Quintano, Carmen Aspiroz, Nuria Prim, and Jesús Rodríguez-Baño
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CARB-ES-19 study ,carbapenemases ,whole genome sequencing ,Klebsiella pneumoniae ,high-risk clones ,Microbiology ,QR1-502 - Abstract
ObjectivesCARB-ES-19 is a comprehensive, multicenter, nationwide study integrating whole-genome sequencing (WGS) in the surveillance of carbapenemase-producing K. pneumoniae (CP-Kpn) and E. coli (CP-Eco) to determine their incidence, geographical distribution, phylogeny, and resistance mechanisms in Spain.MethodsIn total, 71 hospitals, representing all 50 Spanish provinces, collected the first 10 isolates per hospital (February to May 2019); CPE isolates were first identified according to EUCAST (meropenem MIC > 0.12 mg/L with immunochromatography, colorimetric tests, carbapenem inactivation, or carbapenem hydrolysis with MALDI-TOF). Prevalence and incidence were calculated according to population denominators. Antibiotic susceptibility testing was performed using the microdilution method (EUCAST). All 403 isolates collected were sequenced for high-resolution single-nucleotide polymorphism (SNP) typing, core genome multilocus sequence typing (cgMLST), and resistome analysis.ResultsIn total, 377 (93.5%) CP-Kpn and 26 (6.5%) CP-Eco isolates were collected from 62 (87.3%) hospitals in 46 (92%) provinces. CP-Kpn was more prevalent in the blood (5.8%, 50/853) than in the urine (1.4%, 201/14,464). The cumulative incidence for both CP-Kpn and CP-Eco was 0.05 per 100 admitted patients. The main carbapenemase genes identified in CP-Kpn were blaOXA–48 (263/377), blaKPC–3 (62/377), blaVIM–1 (28/377), and blaNDM–1 (12/377). All isolates were susceptible to at least two antibiotics. Interregional dissemination of eight high-risk CP-Kpn clones was detected, mainly ST307/OXA-48 (16.4%), ST11/OXA-48 (16.4%), and ST512-ST258/KPC (13.8%). ST512/KPC and ST15/OXA-48 were the most frequent bacteremia-causative clones. The average number of acquired resistance genes was higher in CP-Kpn (7.9) than in CP-Eco (5.5).ConclusionThis study serves as a first step toward WGS integration in the surveillance of carbapenemase-producing Enterobacterales in Spain. We detected important epidemiological changes, including increased CP-Kpn and CP-Eco prevalence and incidence compared to previous studies, wide interregional dissemination, and increased dissemination of high-risk clones, such as ST307/OXA-48 and ST512/KPC-3.
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- 2022
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4. Carbapenemase-Producing Gram-Negative Bacteria in Andalusia, Spain, 2014–2018
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Inmaculada López-Hernández, Mercedes Delgado-Valverde, Felipe Fernández-Cuenca, Lorena López-Cerero, Jesús Machuca, and Álvaro Pascual
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Acinetobacter baumannii ,AMR ,antimicrobial resistance ,bacteria ,carbapenemases ,Citrobacter freundii ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
The emergence and spread of carbapenemase-producing gram-negative bacteria is a major public health concern. We used data collected from microbiology laboratories as part of the PIRASOA program during 2014–2018 to study the epidemiology of carbapenemase-producing bacteria in Andalusia, Spain. Our findings highlight the importance of ongoing surveillance and epidemiologic studies for these bacteria.
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- 2020
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5. Population Pharmacokinetics of Piperacillin in Non-Critically Ill Patients with Bacteremia Caused by Enterobacteriaceae
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Vicente Merino-Bohórquez, Fernando Docobo-Pérez, Adoración Valiente-Méndez, Mercedes Delgado-Valverde, Manuel Cameán, William W. Hope, Álvaro Pascual, and Jesús Rodríguez-Baño
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bloodstream infection ,renal function ,neurotoxicity ,nephrotoxicity ,pharmacokinetics ,piperacillin–tazobactam ,Therapeutics. Pharmacology ,RM1-950 - 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 > MIC) of 50% for efficacy and targets for piperacillin-associated neurotoxicity. Twenty-seven patients (102 samples) were included. Extended piperacillin infusions reached a PTA > 90% (50%fT > 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.
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- 2021
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6. Mechanisms of Tolerance and Resistance to Chlorhexidine in Clinical Strains of Klebsiella pneumoniae Producers of Carbapenemase: Role of New Type II Toxin-Antitoxin System, PemIK
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Ines Bleriot, Lucia Blasco, Mercedes Delgado-Valverde, Ana Gual-de-Torrella, Anton Ambroa, Laura Fernandez-Garcia, Maria Lopez, Jesus Oteo-Iglesias, Thomas K. Wood, Alvaro Pascual, German Bou, Felipe Fernandez-Cuenca, and Maria Tomas
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tolerance ,persistence ,cross-resistance ,toxin-antitoxin system ,PemI/PemK ,Klebsiella pneumoniae ,Medicine - Abstract
Although the failure of antibiotic treatment is normally attributed to resistance, tolerance and persistence display a significant role in the lack of response to antibiotics. Due to the fact that several nosocomial pathogens show a high level of tolerance and/or resistance to chlorhexidine, in this study we analyzed the molecular mechanisms associated with chlorhexidine adaptation in two clinical strains of Klebsiella pneumoniae by phenotypic and transcriptomic studies. These two strains belong to ST258-KPC3 (high-risk clone carrying β-lactamase KPC3) and ST846-OXA48 (low-risk clone carrying β-lactamase OXA48). Our results showed that the K. pneumoniae ST258-KPC3CA and ST846-OXA48CA strains exhibited a different behavior under chlorhexidine (CHLX) pressure, adapting to this biocide through resistance and tolerance mechanisms, respectively. Furthermore, the appearance of cross-resistance to colistin was observed in the ST846-OXA48CA strain (tolerant to CHLX), using the broth microdilution method. Interestingly, this ST846-OXA48CA isolate contained a plasmid that encodes a novel type II toxin/antitoxin (TA) system, PemI/PemK. We characterized this PemI/PemK TA system by cloning both genes into the IPTG-inducible pCA24N plasmid, and found their role in persistence and biofilm formation. Accordingly, the ST846-OXA48CA strain showed a persistence biphasic curve in the presence of a chlorhexidine-imipenem combination, and these results were confirmed by the enzymatic assay (WST-1).
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- 2020
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7. Brote nosocomial causado por Serratia marcescens en una unidad de cuidados intensivos neonatal de un hospital regional. Análisis y propuestas de mejora
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María Liébana-Rodríguez, Inés Portillo-Calderón, María Amelia Fernández-Sierra, Mercedes Delgado-Valverde, Lina Martín-Hita, and José Gutiérrez-Fernández
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Microbiology (medical) - Published
- 2023
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8. Higher prevalence of CTX-M-27-producing Escherichia coli belonging to ST131 clade C1 among residents of two long-term care facilities in Southern Spain
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José-Manuel Rodríguez-Martínez, Elena Salamanca, Álvaro Pascual, Lorena López-Cerero, Jesús Rodríguez-Baño, Mercedes Delgado-Valverde, Instituto de Salud Carlos III, Ministerio de Economía, Industria y Competitividad (España), Red Española de Investigación en Patología Infecciosa, and European Commission
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Microbiology (medical) ,Veterinary medicine ,medicine.medical_specialty ,ST131 ,Strain (biology) ,CTX-M-27 ,General Medicine ,Biology ,Disease cluster ,medicine.disease_cause ,Long-term care facility ,Infectious Diseases ,Medical microbiology ,medicine ,Clade ,Escherichia coli - Abstract
Recently, the emergence of an international lineage of the CTX-M-27-producing clade C1 of Escherichia coli ST131 is being observed. The aim is to see if this strain has also been introduced in our area. Twenty-eight (33%) out of 86 individuals from two LTCFs in Seville were found to be colonized with fluoroquinolone-resistant E. coli ST131 and 46% isolates were ESBL/pAmpC producers. C1 isolates were more common than C2 and more frequently produced blaESBL/pAmpC genes (53% vs 33%). Strain sharing was observed in 6 groups of 2–5 cases (61%). A differentiated cluster of 5 C1-CTX-M-27 isolates was found which lacked the M27PP1 region., This work was funded by the Plan Nacional de I + D + i 2013–2016 and the Instituto de Salud Carlos III (Acciones Complementarias AC16/00072) supported by the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR) with a One Health approach; and 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 REIPI RD16/0016/0009) co-financed by European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 2014–2020.
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- 2021
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9. Formulation, long-term physicochemical and microbiological stability of 15% topical resorcinol for hidradenitis suppurativa
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Jaime Cordero-Ramos, Rubén Barros-Tornay, Vicente Merino-Bohórquez, Mercedes Delgado-Valverde, Miguel Ángel Calleja-Hernández, and Manuel Cameán-Fenández
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Materials science ,Chemical Phenomena ,Varnish ,Pain ,chemistry.chemical_element ,Resorcinol ,030226 pharmacology & pharmacy ,High-performance liquid chromatography ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Drug Stability ,Aluminium ,Polyethylene terephthalate ,Humans ,030212 general & internal medicine ,General Pharmacology, Toxicology and Pharmaceutics ,Chromatography ,Polyethylene Terephthalates ,Resorcinols ,Amber ,Hidradenitis Suppurativa ,Low-density polyethylene ,chemistry ,Polyethylene ,Compounding ,visual_art ,Emulsion ,visual_art.visual_art_medium ,Emulsions ,Aluminum - Abstract
Objectives Topical resorcinol 15% is a self-treatment for painful hidradenitis suppurativa nodules and abscesses with good results in reducing pain and lesion duration. The aim of this study is to establish a 15% topical resorcinol formula, to develop a physicochemical and microbiological stability study and to further determine the compounding shelf-life in different package conditions following the European Pharmacopoeia (Ph. Eur.) specifications. Methods Physicochemical and microbiological stability studies of the formulation were conducted for 12 months at room temperature (25°C±2°C) in different package conditions: aluminium tubes (aluminium A7-99.7% varnish DF-6172), plastic tubes (low density polyethylene) and amber plastic containers (polyethylene terephthalate). High performance liquid chromatography (HPLC) was developed as a method of indicating the stability of the resorcinol formulation. A microbiological growth assay was also validated according to the Ph. Eur. Physical properties were inspected to determine parameters such as odour, colour, pH, emulsion phase and extensibility index and its evolution. Results The HPLC method was validated according to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines. At day 365, visual inspection remained unchanged only for preparations packaged in aluminium tubes. The pH did not vary by more than 0.3 units in all conditions. The extensibility index decreased in the preparations packaged in plastic and amber plastic containers. HPLC analysis conducted over 1 year did not show a degradation greater than 7% of resorcinol in the preparation in plastic and aluminium packages. The ability of ATCC strains to grow in resorcinol formulation was confirmed under the suitability test. Resorcinol packed in aluminium tubes achieved microbiological stability at day 365. Conclusions Only the formulation package in aluminium tubes showed physicochemical and microbiological stability of resorcinol for 12 months at room temperature (25°C±2°C).
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- 2020
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10. Co-transfer of plasmid-encoded bla carbapenemases genes and mercury resistance operon in high-risk clones of Klebsiella pneumoniae
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Ana Gual-de-Torrella, Jesús Oteo-Iglesias, Álvaro Pascual, Patricia Pérez-Palacios, Mercedes Delgado-Valverde, Felipe Fernández-Cuenca, Ministerio de Sanidad y Consumo (España), Instituto de Salud Carlos III, Red Española de Investigación en Patología Infecciosa, Ministerio de Economía y Competitividad (España), and European Commission
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Whole genome sequencing ,Genetics ,Carbapenemase gene ,Potential impact ,biology ,Klebsiella pneumoniae ,Operon ,General Medicine ,Mercury ,Co-resistance ,biology.organism_classification ,Applied Microbiology and Biotechnology ,Plasmid ,Plasmid dna ,Metals ,Gene ,Bacteria ,Biotechnology - Abstract
Carbapenemase-producing Klebsiella pneumoniae (CP-Kp) is a real global health threat. Environmental reservoirs of resistance gene determinats, such as effluents of hospital wastewaters, are acquiring increased relevance in the selection of plasmid-encoded carbapenemase genes. The presence of Hg in environmental reservoirs may exert a positive selective pressure on tolerant bacteria, favoring the co-transfer of carbapenemase genes and mer operons. In our study, 63 CP-Kp isolates were screened for mer operons by whole genome sequencing (MySeq). Conjugation assays were performed with 24 out of 63 CP-Kp isolates harboring the mer operon. Ten transconjugants (Tc-Kp) were selected with Hg. Plasmid DNA of Tc-Kp was extracted and sequenced using single-molecule real-time (SMRT) technology (PacBio, Sequel II system) with later annotation. Plasmid analysis revealed that Tc-Kp from blaIMP-like (n = 3) showed a single plasmid belonging to IncC group with two complete mer operon next to blaIMP-like. Tc-Kp from blaVIM-1 (n = 2) harbored two plasmids, one with blaVIM-1 in an IncL, and mer operon was in an IncFIB plasmid. Tc-Kp from blaOXA-48-like (n = 5) showed 2 plasmids. blaOXA-48-like was found in an IncL plasmid, whereas mer operon was (i) in an IncR plasmid associated with blaCTX-M-15 in 3 Tc-Kp-OXA-48-like, (ii) in an IncC plasmid associated with blaCMY-2 in 1 Tc-Kp-OXA-48-like, (iii) and in an IncFIB plasmid associated with blaCTX-M-15 in 1 Tc-Kp-OXA-48-like. This is, to our knowledge, the first study to describe in K. pneumoniae producing plasmid-encoded carbapenemase, the potential impact of Hg in the co-transfer of mer operons and carbapenemase genes located in the same or different plasmids., This work was supported by the Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III (project PI15-01172), and the Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía y Competitividad, the Spanish Network for Research in Infectious Diseases (REIPI RD12/0015) co-financed by European Development Regional Fund “A way to achieve Europe” ERDF.
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- 2021
11. Co-transfer of plasmid-encoded bla carbapenemases genes and mercury resistance operon in high-risk clones of Klebsiella pneumoniae
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Patricia, Perez-Palacios, Mercedes, Delgado-Valverde, Ana, Gual-de-Torrella, Jesús, Oteo-Iglesias, Álvaro, Pascual, and Felipe, Fernández-Cuenca
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Klebsiella pneumoniae ,Bacterial Proteins ,Operon ,Humans ,Mercury ,Microbial Sensitivity Tests ,beta-Lactamases ,Clone Cells ,Klebsiella Infections ,Plasmids - Abstract
Carbapenemase-producing Klebsiella pneumoniae (CP-Kp) is a real global health threat. Environmental reservoirs of resistance gene determinats, such as effluents of hospital wastewaters, are acquiring increased relevance in the selection of plasmid-encoded carbapenemase genes. The presence of Hg in environmental reservoirs may exert a positive selective pressure on tolerant bacteria, favoring the co-transfer of carbapenemase genes and mer operons. In our study, 63 CP-Kp isolates were screened for mer operons by whole genome sequencing (MySeq). Conjugation assays were performed with 24 out of 63 CP-Kp isolates harboring the mer operon. Ten transconjugants (Tc-Kp) were selected with Hg. Plasmid DNA of Tc-Kp was extracted and sequenced using single-molecule real-time (SMRT) technology (PacBio, Sequel II system) with later annotation. Plasmid analysis revealed that Tc-Kp from bla
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- 2021
12. Higher prevalence of CTX-M-27-producing Escherichia coli belonging to ST131 clade C1 among residents of two long-term care facilities in Southern Spain
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Lorena, López-Cerero, Elena, Salamanca, Mercedes, Delgado-Valverde, José Manuel, Rodríguez-Martínez, Jesús, Rodríguez-Baño, and Álvaro, Pascual
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Spain ,Escherichia coli Proteins ,Escherichia coli ,Prevalence ,Humans ,Long-Term Care ,Polymorphism, Single Nucleotide ,Escherichia coli Infections ,beta-Lactamases ,Anti-Bacterial Agents - Abstract
Recently, the emergence of an international lineage of the CTX-M-27-producing clade C1 of Escherichia coli ST131 is being observed. The aim is to see if this strain has also been introduced in our area. Twenty-eight (33%) out of 86 individuals from two LTCFs in Seville were found to be colonized with fluoroquinolone-resistant E. coli ST131 and 46% isolates were ESBL/pAmpC producers. C1 isolates were more common than C2 and more frequently produced bla
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- 2021
13. Transfer of plasmids harbouring bla
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Patricia, Perez-Palacios, Ana, Gual-de-Torrella, Mercedes, Delgado-Valverde, Jesús, Oteo-Iglesias, Carmen, Hidalgo-Díaz, Álvaro, Pascual, and Felipe, Fernández-Cuenca
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Klebsiella pneumoniae ,Bacterial Proteins ,Biofilms ,Escherichia coli ,beta-Lactamases ,Disinfectants ,Plasmids - Abstract
The spread of OXA-48-encoding plasmids from Klebsiella pneumoniae (OXA-48-Kpn), especially successful high-risk (HR) clones, is a growing concern. Biofilm formation can contribute to the dissemination of OXA-48-Kpn. It is not known whether biocides can affect the transfer of OXA-48-Kpn in biofilm. The aim of this study was to evaluate the effect of biocides on the conjugation frequency (CF) of OXA-48-Kpn in both biofilm and planktonic cultures. For that, seven OXA-48-Kpn isolates (4 belonging to HR clones and 3 to non-HR clones) were selected as donors. Each isolate was mixed (1:1) with Escherichia coli J53 (recipient) and grown on polystyrene microplates without biocides (control) and with 0.25x MIC of triclosan (TRI), chlorhexidine digluconate (CHX), povidone-iodine (POV), sodium hypochlorite (SOD) or ethanol (ETH). The CF was calculated as the number of transconjugants/number of E. coli J53. The results showed that for isolates growing in the absence of biocide, the mean fold change in the CF in biofilm with respect to that determined in planktonic cells (CF-BF/CF-PK) was 0.2 in non-HR isolates and ranged from 2.0 to 14.7 in HR isolates. In HR isolates grown in the presence of biocide, especially CHX, TRI, and ETH, the fold changes in CF-BF/CF-PK decreased, whereas in non-HR isolates the fold changes were similar or increased slightly with CHX, ETH, SOD and POV. In conclusion, the fold changes in the CF-BF/CF-PK are higher in HR isolates comparing to non-HR isolates in abscence of biocides. The fold changes in CF-BF/CF-PK of the HR isolates in the presence of biocides varied with the type of biocides, whereas in non-HR isolates, biocides have no significant effect, or produce only a slight increase in the fold change of CF-BF/CF-PK.
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- 2021
14. Infecciones en pacientes colonizados con bacterias gramnegativas resistentes a carbapenémicos en una ciudad media española
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Soria-Segarra, Carmen, Mercedes Delgado, Valverde, Serrano-García, María Luisa, Inmaculada López, Hernández, Navarro-Marí, José María, and Gutiérrez-Fernández, José
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Adult ,Carbapenemasas ,Colonization ,Resistencia a carbapenémicos ,Original ,Carbapenemases ,beta-Lactamases ,Anti-Bacterial Agents ,Cross-Sectional Studies ,Bacterial Proteins ,Carbapenems ,Gram-negative bacteria ,Humans ,Bacterias gramnegativas ,Carbapenems resistance ,Colonización ,Multilocus Sequence Typing ,Retrospective Studies - Abstract
[ES] Objetivo. Debido a que existen pocos estudios sobre las implicaciones clínicas de la colonización por bacterias gramne-gativas resistentes a carbapenémicos (BRC) se analizó ésta en frotis rectales (FR) y faríngeos (FF) y su relación con la capacidad de predecir infección/colonización. Material y métodos. Se realizó un estudio transversal, retrospectivo de los pacientes adultos hospitalizados entre enero del 2016 y diciembre del 2019. Los aislamientos fueron caracterizados mediante MicroScan y espectrometría de masas, aplicando los puntos de corte EUCAST 2018. La detección de carbapenemasas se realizó mediante PCR y secuenciación Sanger; se asignó el secuenciotipo mediante MLST. La relación genética entre los aislados se hizo mediante electroforesis de campo pulsado usando las enzimas Xbal, Spel o Apal. Resultados. Se detectaron 308 (86,03 %) FR y 50 (13,97%) FF positivos, teniendo el FR una sensibilidad del 85%, especificidad del 100%, VPP 100% y VPN 97%. En los FR se aislaron: 44% (n=135) Acinetobacter baumannii, 26% (n=80) Enterobacterales (20 KPC, 29 OXA-48, 22 VIM, 2 IMP, 7 NDM), 17% (n=53) Pseudomonas aeruginosa y 13% (n=40) Stenotrophomonas maltophilia. En los FF se aislaron un 44% (n=22) S. maltophilia, 40% (n=20) A. baumannii, 8% (n=4) P. aeruginosa y 8% (n=4) Enterobacterales (3 VIM, 1 OXA). De los pacientes con tomas simultáneas de FR y FF, 41 (40,6%) tuvieron positividad en ambos frotis, 45 (44,6%) sólo en FR y 15 (14,9%) sólo en FF. En el 81,3% (n=13) de los episodios la colonización precedió a la infección, existiendo asociación entre infección y colonización (p, [EN] Objective. Because there are few studies on the clinical implications of colonization by carbapenem-resistant gram-negative bacteria (CRB) this was analyzed in rectal smears (RS) and pharyngeals (PS) and its ability to predict infection/colonization. Methodology. A cross-sectional, retrospective study from adult inpatients between January 2016 and December 2019 was conducted. The isolates were characterized by MicroScan and spectrometry of masses applying EUCAST 2018 cutoff points. The detection of carbapenemases was performed by PCR and Sanger sequencing; sequencies was assigned by MLST. The genetic relationship between the clinical isolates was made by pulsed field electrophoresis using the enzymes Xbal, Spel or Apal. Results. A total of 308 (86.03%) RS and 50 (13.97%) positive PS were detected, the RS had a 85% sensibility, 100% specificity, 100% positive predictive value and 97% negative predictive value. In RS, the following were isolated: 44% (n=135) Acinetobacter baumannii, 26% (n =80) Enterobacterales (20 KPC, 29 OXA-48, 22 VIM, 2 IMP, 7 NDM), 17% (n=53) Pseudomonas aeruginosa and 13% (n=40) Stenotrophomonas maltophilia. In the PS were isolated 44% (n=22) S. maltophilia, 40% (n = 20) A. baumannii, 8% (n=4) P. aeruginosa and 8% (n=4) Enterobacterales (3 VIM, 1 OXA). From the patients with simultaneous RS and PS, 41 (40.6%) had positivity in both smears, 45 (44.6%) only in RS and 15 (14.9%) only in PS. Colonization preceded infection in 81.3% (n=13) of the isolates; association between infection and colonization was found (p
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- 2021
15. Actividad in vitro de seis biocidas frente a Klebsiella pneumoniae productora de carbapenemasa y presencia de genes codificantes de bombas de expulsión
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Felipe Fernández-Cuenca, Álvaro Pascual, Mercedes Delgado-Valverde, Ana Gual-de-Torrella, Jesús Oteo-Iglesias, Patricia Pérez-Palacios, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), and European Commission
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0301 basic medicine ,Microbiology (medical) ,clone (Java method) ,Desinfectantes ,Biocide ,Klebsiella pneumoniae ,030106 microbiology ,Bombas de expulsión ,beta-Lactamases ,Microbiology ,Carbapenemase ,03 medical and health sciences ,Benzalkonium chloride ,chemistry.chemical_compound ,0302 clinical medicine ,High-risk clone ,Bacterial Proteins ,Carbapenemasa ,medicine ,Efflux pumps ,030212 general & internal medicine ,biology ,Ethanol ,Clon de alto riesgo ,biology.organism_classification ,In vitro ,Triclosan ,Carbapenem-Resistant Enterobacteriaceae ,chemistry ,Sodium hypochlorite ,Biocides ,Efflux ,Benzalkonium Compounds ,medicine.drug ,Disinfectants - Abstract
[Introduction] Acquisition of reduced susceptibility to biocides may contribute to the dissemination of high-risk (HR) clones of carbapenemase-producing Klebsiella pneumoniae (CP-Kp). The aim of this study was (a) to determinate the activity of biocides against CP-Kp, and (b) to analyse the relationship between biocide activity and the presence of efflux pumps., [Methods] The minimal inhibitory concentrations (MICs) of 6 biocides (sodium hypochlorite, chlorhexidine digluconate, benzalkonium chloride, povidone-iodine, ethanol and triclosan) were determined in triplicate at 25 °C and 37 °C in Mueller-Hinton broth (MHB) and M9 minimum medium, against 17 CP-Kp isolates representing different clones (HR and no-HR), sequence-types (STs) and carbapenemases. Efflux pumps genes were detected by whole genome sequencing (MiSeq)., [Results] Median MICs were slightly higher at 37 °C than at 25 °C (p ≤ 0.05), except for benzalkonium chloride, triclosan and ethanol. MIC medians were much higher in MHB than in M9, except for triclosan. No significant differences were observed in the median MICs, regarding the type of clone, ST or carbapenemase; cepA, acrAB, kpnEF and oqxAB genes were detected in all isolates, whereas qacE and qacA were not detected; smvAR, and qacΔE genes were detected in 94% and 47% of isolates, respectively., [Conclusions] Triclosan, chlorhexidine digluconate, benzalkonium chloride and ethanol were the most active biocides. The activity of some biocides is affected by temperature and growth media, suggesting that standardised procedures for biocide susceptibility testing based on MIC determination are required. This activity, in terms of MICs, are not related to the type of clone, ST, carbapenemase or the presence of the efflux pump genes., [Introducción] La adquisición de sensibilidad reducida a los biocidas puede contribuir a la diseminación de clones de alto riesgo (HR) de Klebsiella pneumoniae productor de carbapenemasa (Kp-PC). El objetivo de este trabajo fue: (a) determinar la actividad de varios biocidas frente a Kp-PC, y (b) analizar la relación de dicha actividad con la presencia de genes codificantes de bombas de expulsión., [Métodos] Las concentraciones mínimas inhibitorias (CMI) de 6 biocidas (hipoclorito de sodio, digluconato de clorhexidina, cloruro de benzalconio, povidona yodada, etanol y triclosán) se determinaron por triplicado a 25 y 37 °C, tanto en caldo Mueller-Hinton (MHB) como en medio mínimo M9, frente a 17 aislados de Kp-PC representativos de diferentes clones (HR y no HR), secuenciotipos (ST) y carbapenemasas. Los genes de bombas de expulsión se detectaron mediante secuenciación masiva del genoma completo (MiSeq)., [Resultados] Las medianas de las CMI fueron ligeramente superiores a 37 °C que a 25 °C, excepto para cloruro de benzalconio, etanol y triclosán. Las medianas de las CMI fueron considerablemente superiores en MHB que en M9, excepto para triclosán; cepA, acrAB, kpnEF y oqxAB se detectaron en todos los aislados, mientras que qacE y qacA no se detectaron; smvAR y qacΔE se detectaron en el 94% y en el 47% de los aislados, respectivamente., [Conclusiones] La actividad de algunos biocidas se afecta por la temperatura y el medio de crecimiento. Esta actividad, en términos de CMI, no se relaciona con el tipo de clon, ST, carbapenemasa, ni con la presencia de genes que codifican bombas de expulsión., This study was funded by a grant (PI15-01172) from Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía Industria y Competitividad, the Spanish Network for Research in Infectious Diseases (RD16/0016/0001)-co-financed by European Development Regional Fund «A way to achieve Europe», Operative program Intelligent Growth 2014-2020.
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- 2021
16. Population Pharmacokinetics of Piperacillin in Non-Critically Ill Patients with Bacteremia Caused by Enterobacteriaceae
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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.
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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 >, MIC) of 50% for efficacy and targets for piperacillin-associated neurotoxicity. Twenty-seven patients (102 samples) were included. Extended piperacillin infusions reached a PTA >, 90% (50%fT >, 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.
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- 2021
17. Molecular characterisation of an outbreak of NDM-7-producing Klebsiella pneumoniae reveals ST11 clone expansion combined with interclonal plasmid dissemination
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Jesús Machuca, Lorena Lopez-Cerero, Manuel Rodríguez-Maresca, Felipe Fernández-Cuenca, Inmaculada López-Hernández, Mercedes Delgado-Valverde, Waldo Sanchez-Yebra, Álvaro Pascual, Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), Red Española de Investigación en Patología Infecciosa, European Commission, Machuca, Jesús, López-Cerero, Lorena, and Delgado-Valverde, Mercedes
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Microbiology (medical) ,NDM-7 ,Microbial Sensitivity Tests ,General Medicine ,Interclonal dissemination ,beta-Lactamases ,Anti-Bacterial Agents ,Clone Cells ,Electrophoresis, Gel, Pulsed-Field ,Klebsiella Infections ,Klebsiella pneumoniae ,Infectious Diseases ,Bacterial Proteins ,Humans ,Pharmacology (medical) ,Multilocus Sequence Typing ,Plasmids - Abstract
The aim of this study was to characterise a hospital outbreak of NDM-7-producing Klebsiella pneumoniae associated with the successful multidrug-resistant (MDR) high-risk clone ST11 between 2017 and 2019 in southern Spain. A total of 46 NDM-7-producing isolates were recovered during the outbreak, including 16 from clinical samples, 27 from surveillance samples and 3 from environmental samples. All isolates were MDR, including carbapenem-resistant. Pulsed-field gel electrophoresis using XbaI restriction enzyme (XbaI-PFGE) showed three pulsotypes belonging to three different clones by multilocus sequence typing (MLST): ST307 (1 isolate); ST152 (1 isolate); and ST11 (44 isolates). Representative isolates were selected for characterisation of blaNDM-7-carrying plasmids using PCR-based replicon typing and whole-genome sequencing analysis. IncX3 plasmids containing NDM-7 were identified in the three clones. The blaNDM-7-carrying plasmids from the ST307 and ST11 clones were identical and were very similar to the IncX3 NDM-7 plasmid previously described. The NDM-7 carbapenemase was introduced into the hospital by means of the ST307 clone, while the ST11 high-risk clone was responsible for NDM-7 dissemination. It is essential to develop and implement strategies to control the introduction and spread of successful MDR clones in hospitals that include active surveillance programmes to detect colonised patients., This work was supported by the Plan Nacional de IDi 2013–2016 and the 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), co-financed by the European Regional Development Fund ‘A way to achieve Europe’, operative program Intelligent Growth 2014–2020.
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- 2022
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18. Carbapenemase-Producing Gram-Negative Bacteria in Andalusia, Spain, 2014-2018
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Álvaro Pascual, Felipe Fernández-Cuenca, Jesús Machuca, Lorena López-Cerero, Inmaculada López-Hernández, and Mercedes Delgado-Valverde
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phenyl boronic acid ,Acinetobacter baumannii ,Epidemiology ,lcsh:Medicine ,dipicolinic acid ,molecular epidemiology ,0302 clinical medicine ,AMR ,030212 general & internal medicine ,bacteria ,biology ,Dispatch ,Klebsiella oxytoca ,gram-negative bacteria ,Anti-Bacterial Agents ,Citrobacter freundii ,Klebsiella pneumoniae ,Infectious Diseases ,Pseudomonas aeruginosa ,Microbiology (medical) ,medicine.medical_specialty ,Gram-negative bacteria ,carbapenemases ,030231 tropical medicine ,Microbial Sensitivity Tests ,beta-Lactamases ,lcsh:Infectious and parasitic diseases ,03 medical and health sciences ,Antibiotic resistance ,Bacterial Proteins ,Environmental health ,Gram-Negative Bacteria ,Enterobacter cloacae ,medicine ,Escherichia coli ,lcsh:RC109-216 ,antimicrobial resistance ,Molecular epidemiology ,Bacteria ,Public health ,lcsh:R ,Carbapenemase producing ,biology.organism_classification ,PIRASOA ,cloxacillin ,Spain ,Carbapenemase-Producing Gram-Negative Bacteria in Andalusia, Spain, 2014–2018 - Abstract
The emergence and spread of carbapenemase-producing gram-negative bacteria is a major public health concern. We used data collected from microbiology laboratories as part of the PIRASOA program during 2014–2018 to study the epidemiology of carbapenemase-producing bacteria in Andalusia, Spain. Our findings highlight the importance of ongoing surveillance and epidemiologic studies for these bacteria.
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- 2020
19. 3PC-002 Microbiological stability test of 15% topical resorcinol for quality control
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Mercedes Delgado-Valverde, Jaime Cordero-Ramos, C Castillo-Martin, Vicente Merino-Bohórquez, FJ Falcón-Rodríguez, and M Cameán-Fernández
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food.ingredient ,biology ,Pseudomonas aeruginosa ,Resorcinol ,Sodium metabisulfite ,medicine.disease_cause ,biology.organism_classification ,Purified water ,chemistry.chemical_compound ,food ,chemistry ,Staphylococcus aureus ,medicine ,Agar ,Trypticase soy agar ,Food science ,Candida albicans - Abstract
Background and importance Hidradenitis suppurativa (HS) is an inflammatory skin disease that causes painful boils and abscess formation, especially localised in intertriginous areas. Resorcinol is a phenol derivate, and in topical self-treatment decreases the size and pain of HS lesions. Topical 15% resorcinol is prepared as a pharmaceutical compound and there are no data in the current literature on the microbiological stability of formulations of topical resorcinol 15%. The European Pharmacopoeia (EP) established acceptance criteria (chapter 5.1.4) for microbiological quality control of the compound. Previous to the microbiological quality assay, the EP also established the necessity of a suitability test of the method. Aim and objectives The objective of the study was to develop a microbiological growth assay to perform a microbiological stability test for quality control of this resorcinol formulation. Material and methods The composition of the formulation of topical resorcinol 15% tested was: resorcinol 15 g, purified water 15 g, sodium metabisulfite 0.1 g and lanette base cream qs 100 g. To determine the ability of microorganisms to grow in the formulation, several reference strains, according to the EP (chapters 2.6.12 and 2.6.13) were selected: Pseudomonas aeruginosa (ATCCVR 9027TM), Candida albicans (ATCCVR 10231TM), Aspergillus brasiliensis (ATCCVR 16404TM) and Staphylococcus aureus (ATCCVR 6538TM). To perform the growth assay, trypticase soy agar (TSA) were used for P aeruginosa and S aureus, and sabouraud glucose agar (SAB) for C albicans and A brasiliensis. The test was performed by taking a 1:1000 dilution of 1 g of topical resorcinol in a 0.1% Tween 80 and phosphate buffered saline solution and adding 100 µL of a suspension equivalent to 1×103 cfu/mL of every ATCC strain, which were inoculated in TSA or SAB. All tests were done in duplicate and medium lectures were made in 48 hours. Results The ability of ATCC strains to growth in resorcinol formulation was confirmed under the study conditions. There was mean growth of 17×104 cfu/mL for S aureus and 11×104 cfu/mL for P aeruginosa in TSA. For A brasiliensis and C albicans, 1×104 cfu/mL and 2×104 cfu/mL were detected, respectively. Conclusion and relevance The presented method shows a simplified way to test the microbiological viability of 15% topical resorcinol for quality control. References and/or acknowledgements No conflict of interest.
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- 2020
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20. Activity of cefiderocol against high-risk clones of multidrug-resistant Enterobacterales, Acinetobacter baumannii, Pseudomonas aeruginosa and Stenotrophomonas maltophilia
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Lara Serrano, Álvaro Pascual, Felipe Fernández-Cuenca, M del Carmen Conejo, Mercedes Delgado-Valverde, Universidad de Sevilla. Departamento de Microbiología, and Shionogi
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Microbiology (medical) ,Acinetobacter baumannii ,Klebsiella pneumoniae ,Avibactam ,Cefepime ,Stenotrophomonas maltophilia ,Ceftazidime ,Microbial Sensitivity Tests ,Biology ,Microbiology ,chemistry.chemical_compound ,Drug Resistance, Multiple, Bacterial ,medicine ,polycyclic compounds ,Pharmacology (medical) ,Original Research ,Pharmacology ,biochemical phenomena, metabolism, and nutrition ,biology.organism_classification ,bacterial infections and mycoses ,Anti-Bacterial Agents ,Cephalosporins ,Clone Cells ,Infectious Diseases ,chemistry ,Spain ,Pseudomonas aeruginosa ,bacteria ,Ceftolozane ,Enterobacter cloacae ,medicine.drug - Abstract
[Background] Cefiderocol is a novel siderophore cephalosporin, developed for activity against MDR Gram-negative bacilli (MDR-GNB)., [Objectives] To assess the in vitro antibacterial activity of cefiderocol against a collection of MDR-GNB clinical isolates from hospitals in southern Spain., [Methods] Two hundred and thirty-one isolates of successful clones were tested: 125 Enterobacterales (121 ESBL- and/or carbapenemase-producing Klebsiella pneumoniae and 4 carbapenemase-producing Enterobacter cloacae), 80 Acinetobacter baumannii, 6 Pseudomonas aeruginosa and 20 Stenotrophomonas maltophilia. Ceftolozane/tazobactam, ceftazidime, ceftazidime/avibactam, cefepime, aztreonam, meropenem, amikacin, ciprofloxacin, colistin and tigecycline were used as comparators against Enterobacterales, P. aeruginosa and A. baumannii. Minocycline, levofloxacin and trimethoprim/sulfamethoxazole were studied against S. maltophilia instead of aztreonam, ciprofloxacin and cefepime. MICs were determined by broth microdilution according to CLSI guidelines. MIC determination was performed in CAMHB for all antimicrobials except cefiderocol, where iron-depleted CAMHB was used., [Results] Cefiderocol showed potent in vitro activity against the isolates analysed. MIC50 and MIC90 values were in the ranges 0.125–8 mg/L and 0.5–8 mg/L, respectively, and 98% of isolates were inhibited at ≤4 mg/L. Only five isolates showed cefiderocol MICs of >4 mg/L: three ST2/OXA-24/40-producing A. baumannii, one ST114/VIM-1-producing E. cloacae and one ST114/VIM-1 + OXA-48-producing E. cloacae. All KPC-3-producing K. pneumoniae were susceptible to cefiderocol, even those resistant to ceftazidime/avibactam. P. aeruginosa isolates showed cefiderocol MICs of, [Conclusions] Cefiderocol showed excellent activity against MDR-GNB, including carbapenem-resistant isolates, and was the most active antimicrobial tested against this collection., This study was partially supported by Shionogi B. V.
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- 2020
21. Physicochemical and microbiological stability of two new oral liquid formulations of clonidine hydrochloride for pediatric patients
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Mercedes Delgado-Valverde, C Cañete, M García-Palomo, M C Dávila-Pousa, Vicente Merino-Bohórquez, M Villaronga, R López-Rojas, M Cameán-Fernández, B Rodriguez-Marrodán, and Sociedad Española de Farmacia Hospitalaria
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Chemical Phenomena ,Drug Compounding ,Administration, Oral ,Pharmaceutical Science ,Compounding ,02 engineering and technology ,Microbiology ,030226 pharmacology & pharmacy ,Clonidine ,03 medical and health sciences ,0302 clinical medicine ,Drug Stability ,Escherichia coli ,medicine ,Humans ,Child ,skin and connective tissue diseases ,Analgesics ,business.industry ,General Medicine ,021001 nanoscience & nanotechnology ,Clonidine Hydrochloride ,Pharmaceutical Solutions ,Anesthesia ,Pseudomonas aeruginosa ,sense organs ,HPLC ,0210 nano-technology ,business ,Stability ,medicine.drug - Abstract
The Pharmaceutical Technology Working Group and Pediatric Pharmacy Working Group of the Spanish Society of Hospital Pharmacy (SEFH)., Pediatric patients present changing physiological features. Because of the lack of land suitable for commercial management, pediatric specialties very often need to prepare extemporaneous formulations to improve the dosage and administration of drugs for children. Oral liquid formulations are the most suitable for pediatric patients. Clonidine is widely used in the pediatric population for opioid withdrawal, hypertensive crisis, attention deficit disorders and hyperactivity syndrome, and as an analgesic in neuropathic cancer pain. The objective was to study the physicochemical and microbiological stability and determine the shelf life of an oral solution containing 20 µg/mL clonidine hydrochloride in different storage conditions (5 ± 3 °C, 25 ± 3 °C, and 40 ± 2 °C). Using raw material with excipients safe for all pediatric age groups, two oral liquid formulations of clonidine hydrochloride were designed (with and without preservatives). Solutions stored at 5 ± 3 °C (with and without preservatives) were physically and microbiologically stable for at least 90 days in closed containers and for 42 days after opening. Two oral solutions of clonidine hydrochloride 20 µg/mL were developed for pediatric use from raw materials that are readily available and easy to process, containing safe excipients that are stable over a long period of time., This work was supported by Spanish Society of Hospital Pharmacy.
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- 2018
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22. Impact of De-escalation on Prognosis of Patients With Bacteremia due to Enterobacteriaceae: A Post Hoc Analysis From a Multicenter Prospective Cohort
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Adoración Valiente Méndez, Álvaro Pascual, Benito Almirante, Lucía Ramos, Cristina de la Calle, Juan E. Corzo, Manuel Causse, José Molina, María Isabel Morosini, Jesús Rodríguez-Baño, Silvia Gómez-Zorrilla, M. Gurguí, Mónica Gozalo, Mercedes Delgado-Valverde, Nuria Borrell, Lara García-Álvarez, Zaira R. Palacios-Baena, and Reipi
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0301 basic medicine ,Microbiology (medical) ,Male ,medicine.medical_specialty ,bloodstream infections ,030106 microbiology ,Bacteremia ,Meropenem ,03 medical and health sciences ,0302 clinical medicine ,Enterobacteriaceae ,Internal medicine ,medicine ,Odds Ratio ,Humans ,030212 general & internal medicine ,Prospective Studies ,Mortality ,Prospective cohort study ,Aged ,Proportional Hazards Models ,Proportional hazards model ,business.industry ,Hazard ratio ,Enterobacteriaceae Infections ,Odds ratio ,Middle Aged ,Prognosis ,mortality ,Confidence interval ,streamlining ,de-escalation ,Infectious Diseases ,Propensity score matching ,Cohort ,Female ,business ,medicine.drug - Abstract
Background More data are needed about the safety of antibiotic de-escalation in specific clinical situations as a strategy to reduce exposure to broad-spectrum antibiotics. The aims of this study were to investigate predictors of de-escalation and its impact on the outcome of patients with bloodstream infection due to Enterobacteriaceae (BSI-E). Methods A post hoc analysis was performed on a prospective, multicenter cohort of patients with BSI-E initially treated with ertapenem or antipseudomonal β-lactams. Logistic regression was used to analyze factors associated with early de-escalation (EDE) and Cox regression for the impact of EDE and late de-escalation (LDE) on 30-day all-cause mortality. A propensity score (PS) for EDE vs no de-escalation (NDE) was calculated. Failure at end of treatment and length of hospital stay were also analyzed. Results Overall, 516 patients were included. EDE was performed in 241 patients (46%), LDE in 95 (18%), and NDE in 180 (35%). Variables independently associated with a lower probability of EDE were multidrug-resistant isolates (odds ratio [OR], 0.50 [95% confidence interval {CI}, .30–.83]) and nosocomial infection empirically treated with imipenem or meropenem (OR, 0.35 [95% CI, .14–.87]). After controlling for confounders, EDE was not associated with increased risk of mortality; hazard ratios (HR) (95% CIs) were as follows: general model, 0.58 (.25–1.31); model with PS, 0.69 (.29–1.65); and PS-based matched pairs, 0.98 (.76–1.26). LDE was not associated with mortality. De-escalation was not associated with clinical failure or length of hospital stay. Conclusions De-escalation in patients with monomicrobial bacteremia due to Enterobacteriaceae was not associated with a detrimental impact on clinical outcome.
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- 2018
23. Impact of the MIC of piperacillin/tazobactam on the outcome for patients with bacteraemia due to Enterobacteriaceae: The Bacteraemia-MIC project
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José Miguel Cisneros, Mercedes Delgado-Valverde, Andras Farkas, Fe Tubau Quintano, Carmen Peña, Mohd-Hafiz Abdul-Aziz, Adoración Valiente-Mendez, Jason A. Roberts, M. Isabel Morosini, Manuel Almela, Luis Martínez-Martínez, Nuria Borrell, Rafael Cantón, Juan E. Corzo, Julia Praena, María Cruz Fontecoba-Sánchez, Benito Almirante, Manuel Causse, Ana Maria Planes Reig, Álvaro Pascual, M. Gurguí, Eva Torres, Marina de Cueto, M. Elvira Galán Otalora, Lara García-Álvarez, Shawna Morey, Silvia Gómez-Zorrilla, Belén Gutiérrez-Gutiérrez, Carlos Ruiz de Alegría, José Antonio Lepe, Jesús Rodríguez-Baño, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), European Commission, Red Española de Investigación en Patología Infecciosa, and National Health and Medical Research Council (Australia)
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Adult ,Male ,0301 basic medicine ,Microbiology (medical) ,medicine.medical_specialty ,genetic structures ,Adolescent ,030106 microbiology ,Penicillanic Acid ,Bacteremia ,Microbial Sensitivity Tests ,Tazobactam ,Hospitals, University ,Young Adult ,03 medical and health sciences ,Enterobacteriaceae ,Internal medicine ,polycyclic compounds ,medicine ,Humans ,Pharmacology (medical) ,Prospective Studies ,Prospective cohort study ,Survival analysis ,Aged ,Aged, 80 and over ,Piperacillin ,Pharmacology ,business.industry ,Enterobacteriaceae Infections ,Middle Aged ,bacterial infections and mycoses ,medicine.disease ,Survival Analysis ,Surgery ,Piperacillin, Tazobactam Drug Combination ,Treatment Outcome ,Infectious Diseases ,Spain ,Relative risk ,Piperacillin/tazobactam ,Female ,business ,medicine.drug ,Cohort study - Abstract
[Objective] Our objective was to evaluate the impact of low versus borderline MIC of piperacillin/tazobactam on the clinical outcomes of patients with bacteraemia caused by Enterobacteriaceae who were treated with that antimicrobial., [Patients and methods] A prospective observational multicentre cohort study was conducted in 13 Spanish university hospitals. Patients >17 years old with bacteraemia due to Enterobacteriaceae who received empirical piperacillin/tazobactam treatment for at least 48 h were included. Outcome variables were clinical response at day 21, clinical response at end of treatment with piperacillin/tazobactam and all-cause 30 day mortality. Univariate and multivariate logistic regression analyses were performed., [Results] Overall, 275 patients were included in the analysis; 248 (90.2%) in the low MIC group (≤4 mg/L) and 27 (9.8%) in the borderline MIC group (8–16 mg/L). The biliary tract was the most common source of infection (48.4%) and Escherichia coli was the most frequent pathogen (63.3%). Crude 30 day mortality rates were 10.5% and 11.1% for the low MIC group and the borderline MIC group, respectively (relative risk = 1.06, 95% CI = 0.34–3.27, P = 1). Multivariate analysis of failure at day 21 and at end of treatment with piperacillin/tazobactam and 30 day mortality showed no trend towards increased clinical failure or mortality with borderline MICs (OR = 0.96, 95% CI = 0.18–4.88, P = 0.96; OR = 0.47, 95% CI = 0.10–2.26, P = 0.35; OR = 1.48, 95% CI = 0.33–6.68, P = 0.6)., [Conclusions] We did not find that higher piperacillin/tazobactam MIC within the susceptible or intermediate susceptibility range had a significant influence on the outcome for patients with bacteraemia due to Enterobacteriaceae., The study was funded by the Instituto de Salud Carlos III, Ministry of Economy and Competitiveness, Spain (FIS; PI10/02021) co-financed by European Development Regional Fund ‘A way to achieve Europe’ ERDF, Spanish Network for Research in Infectious Diseases (REIPI RD12/0015). J. A. R. is funded, in part, by an Australian National Health and Medical Research Council Research Fellowship (APP1048652).
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- 2016
24. Variantes pequeñas de Staphylococcus aureus: utilidad de distintas pruebas para su diagnóstico y estudio de sensibilidad
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Mercedes Delgado-Valverde, Nínive Batista-Díaz, Álvaro Pascual-Hernández, and Pedro Fernández-Echauri
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Microbiology (medical) - Abstract
Resumen Introduccion Las variantes de colonia pequena de Staphylococcus aureus (VCPSA) constituyen una subpoblacion con caracteristicas especiales. Metodos Se estudio el comportamiento fenotipico y la sensibilidad antibiotica de 4 aislados clinicos de VCPSA. Resultados Las colonias crecieron en los medios de cultivo habituales excepto en Mueller Hinton. Todos los aislados fueron resistentes a ciprofloxacino y cotrimoxazol. Discusion Las VCPSA son aisladas con baja frecuencia, y es necesario conocer los metodos optimos para su identificacion y el estudio de su sensibilidad antibiotica.
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- 2014
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25. [Small-colony variants of Staphylococcus aureus: Usefulness of various test for diagnosis and susceptibility study]
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Mercedes, Delgado-Valverde, Pedro, Fernández-Echauri, Nínive, Batista-Díaz, and Alvaro, Pascual-Hernández
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Bacteriological Techniques ,Staphylococcus aureus ,Cystic Fibrosis ,Colony Count, Microbial ,Sputum ,Vitamin K 3 ,Microbial Sensitivity Tests ,Staphylococcal Infections ,Anti-Bacterial Agents ,Clone Cells ,Culture Media ,Phenotype ,Drug Resistance, Multiple, Bacterial ,Hemin ,Humans ,Otitis ,Thymidine - Abstract
Small colony variants of Staphylococcus aureus (SCVSA) are a sub-population with special features.The phenotypic features and antibiotic susceptibility of four clinical isolates SCVSA were studied.Colonies grew in the usual culture media, except in Mueller Hinton. All isolates were resistant to ciprofloxacin and co-trimoxazole.As SCVSA are isolated with low frequency, it is necessary to determine the optimal methods for their identification and antibiotic susceptibility study.
- Published
- 2012
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