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1. Propensity Score and Desirability of Outcome Ranking Analysis of Ertapenem for Treatment of Nonsevere Bacteremic Urinary Tract Infections Due to Extended-Spectrum-Beta-Lactamase-Producing Enterobacterales in Kidney Transplant Recipients

Author

Gutierrez-Gutierrez, B., Perez-Nadales, E., Perez-Galera, S., Fernandez-Ruiz, M., Carratala, J., Oriol, I., Cordero, E., Lepe, J. A., Tan, B. H., Corbella, L., Paul, M., Natera, A. M., David, M. D., Montejo, M., Iyer, R. N., Pierrotti, L. C., Merino, E., Steinke, S. M., Rana, M. M., Munoz, P., Mularoni, A., van Delden, C., Grossi, P. A., Seminari, E. M., Gunseren, F., Lease, E. D., Roilides, E., Fortun, J., Arslan, H., Coussement, J., Tufan, Z. K., Pilmis, B., Rizzi, M., Loeches, B., Eriksson, B. M., Abdala, E., Soldani, F., Lowman, W., Clemente, W. T., Bodro, M., Farinas, M. C., Kazak, E., Martinez-Martinez, L., Aguado, J. M., Torre-Cisneros, J., Pascual, A., Rodriguez-Bano, J., Sabe, N., Camoez, M., Martin-Gandul, C., Bernal, G., Kee, T. Y. S., Lopez-Medrano, F., Juan, R. S., Koppel, F., Bar-Sinai, N., Caston, J. J., Cano, A., Gracia-Ahufinger, I., Rodriguez, R., Lopez-Soria, L., Azurmendi, M., Pinheiro, M., Freire, M., Banks, I., Lopes, F., David-Neto, E., Balibrea, N., Franco, A., Avery, R., Ostrander, D., Minero, M. V., Carrillo, C. S., Rodriguez-Ferrero, M. L., Monaco, F., Campanella, M., Mueller, N. J., Manuel, O., Khanna, N., Rovelli, C., Balsamo, M. L., Colombo, A., Leoni, C., Pyrpasopoulou, A., Mouloudi, E., Iosifidis, E., Martin-Davila, P., Gioia, F., Escudero, R., Demirkaya, M. H., Dewispelaere, L., Kalem, A. K., Hasanoglu, I., Guner, R., Lortholary, O., Scemla, A., Calvi, E. G., Gervasi, E., Binda, F., Oliva, M. L., Dimopoulos, N., Magalhaes, M. R., Song, A. T. W., D'Albuquerque, L. A. C., Chiesi, S., Salerno, N. D., Mourao, P. H. O., Moreno, A., Linares, L., Almela, M., Rico, C. G., Rodrigo, E., Martinez, M. F., Falcone, M., Tumbarello, M., Strabelli, T. M. V., Instituto de Salud Carlos III, Ministerio de Ciencia, Innovación y Universidades (España), Red Española de Investigación en Patología Infecciosa, European Commission, Sociedad Andaluza de Trasplante de Órganos y Tejidos, and Ministerio de Ciencia e Innovación (España)

Subjects
Ertapenem, medicine.medical_specialty, Urinary system, UTI, Bacteremia, Bloodstream infection, BSI, Logistic regression, Extended-spectrum-b-lactamase-producing Enterobacterales, Meropenem, beta-Lactamases, Cohort Studies, chemistry.chemical_compound, Internal medicine, polycyclic compounds, medicine, Humans, Pharmacology (medical), Propensity Score, Kidney transplant, Retrospective Studies, Pharmacology, Urinary tract infection, business.industry, ESBL-E, Anti-Bacterial Agents, Kidney Transplantation, Urinary Tract Infections, bacterial infections and mycoses, medicine.disease, Infectious Diseases, chemistry, Propensity score matching, Cohort, business, medicine.drug, Cohort study
Abstract

REIPI/ESGICH/ESGBIS/INCREMENT-SOT Group., There are scarce data on the efficacy of ertapenem in the treatment of bacteremia due to extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) in kidney transplant (KT) recipients. We evaluated the association between treatment with ertapenem or meropenem and clinical cure in KT recipients with nonsevere bacteremic urinary tract infections (B-UTI) caused by ESBL-E. We performed a registered, retrospective, international (29 centers in 14 countries) cohort study (INCREMENT-SOT, NCT02852902). The association between targeted therapy with ertapenem versus meropenem and clinical cure at day 14 (the principal outcome) was studied by logistic regression. Propensity score matching and desirability of outcome ranking (DOOR) analyses were also performed. A total of 201 patients were included; only 1 patient (treated with meropenem) in the cohort died. Clinical cure at day 14 was reached in 45/100 (45%) and 51/101 (50.5%) of patients treated with ertapenem and meropenem, respectively (adjusted OR 1.29; 95% CI 0.51 to 3.22; P = 0.76); the propensity score-matched cohort included 55 pairs (adjusted OR for clinical cure at day 14, 1.18; 95% CI 0.43 to 3.29; P = 0.74). In this cohort, the proportion of cases treated with ertapenem with better DOOR than with meropenem was 49.7% (95% CI, 40.4 to 59.1%) when hospital stay was considered. It ranged from 59 to 67% in different scenarios of a modified (weights-based) DOOR sensitivity analysis when potential ecological advantage or cost was considered in addition to outcome. In conclusion, targeted therapy with ertapenem appears as effective as meropenem to treat nonsevere B-UTI due to ESBL-E in KT recipients and may have some advantages., This work was supported by Plan Nacional de I+D+i 2013‐2016 and Instituto de Salud Carlos III (ISCIII), 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, RD16/0016/0002, RD16/0016/0008; RD16/0016/00010) and was cofinanced by the European Development Regional Fund “A way to achieve Europe,” Operative program Intelligent Growth 2014‐2020; ESCMID Study Group for Infections in Compromised Hosts (ESGICH grant to J.M.A.); Sociedad Andaluza de Trasplante de Órgano Sólido (SATOT grant to L.M.-M.); ESCMID Study Group for Bloodstream Infections and Sepsis (ESGBIS); and ESCMID Study Group for Antimicrobial Resistance Surveillance (ESGARS). B.G.-G. (PI 18/01849) and E.P.-N. (PI 16/01631) have received research funds from the Spanish Ministry of Science and Innovation, ISCIII; M.F.-R. holds a research contract “Miguel Servet” (CP 18/00073) from the Spanish Ministry of Science and Innovation, ISCIII.

Published
2021

2. Propensity Score and Desirability of Outcome Ranking Analysis of Ertapenem for Treatment of Nonsevere Bacteremic Urinary Tract Infections Due to Extended-Spectrum-Beta-Lactamase-Producing Enterobacterales in Kidney Transplant Recipients

Author

Gutierrez-Gutierrez B, Perez-Nadales E, Perez-Galera S, Fernandez-Ruiz M, Carratala J, Oriol I, Cordero E, Lepe J, Tan B, Corbella L, Paul M, Natera A, David M, Montejo M, Iyer R, Pierrotti L, Merino E, Steinke S, Rana M, Munoz P, Mularoni A, van Delden C, Grossi P, Seminari E, Gunseren F, Lease E, Roilides E, Fortun J, Arslan H, Coussement J, Tufan Z, Pilmis B, Rizzi M, Loeches B, Eriksson B, Abdala E, Soldani F, Lowman W, Clemente W, Bodro M, Farinas M, Kazak E, Martinez-Martinez L, Aguado J, Torre-Cisneros J, Pascual A, Rodriguez-Bano J, and Investigators REIPI ESGICH ESGBIS

Subjects
kidney transplant, ertapenem, UTI, bloodstream infection, BSI, urinary tract infection, extended-spectrum-beta-lactamase-producing Enterobacterales, ESBL-E
Abstract

There are scarce data on the efficacy of ertapenem in the treatment of bacteremia due to extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) in kidney transplant (KT) recipients. We evaluated the association between treatment with ertapenem or meropenem and clinical cure in KT recipients with nonsevere bacteremic urinary tract infections (B-UTI) caused by ESBL-E. We performed a registered, retrospective, international (29 centers in 14 countries) cohort study (INCREMENT-SOT, NCT02852902). The association between targeted therapy with ertapenem versus meropenem and clinical cure at day 14 (the principal outcome) was studied by logistic regression. Propensity score matching and desirability of outcome ranking (DOOR) analyses were also performed. A total of 201 patients were included; only 1 patient (treated with meropenem) in the cohort died. Clinical cure at day 14 was reached in 45/100 (45%) and 51/101 (50.5%) of patients treated with ertapenem and meropenem, respectively (adjusted OR 1.29; 95% CI 0.51 to 3.22; P = 0.76); the propensity score-matched cohort included 55 pairs (adjusted OR for clinical cure at day 14, 1.18; 95% CI 0.43 to 3.29; P = 0.74). In this cohort, the proportion of cases treated with ertapenem with better DOOR than with meropenem was 49.7% (95% CI, 40.4 to 59.1%) when hospital stay was considered. It ranged from 59 to 67% in different scenarios of a modified (weights-based) DOOR sensitivity analysis when potential ecological advantage or cost was considered in addition to outcome. In conclusion, targeted therapy with ertapenem appears as effective as meropenem to treat nonsevere B-UTI due to ESBL-E in KT recipients and may have some advantages.

Published
2021

3. Predictors of mortality in solid organ transplant recipients with bloodstream infections due to carbapenemase-producing Enterobacterales: The impact of cytomegalovirus disease and lymphopenia

Author

Perez-Nadales, E., Gutierrez-Gutierrez, B., Natera, A. M., Abdala, E., Reina Magalhaes, M., Mularoni, A., Monaco, F., Camera Pierrotti, L., Pinheiro Freire, M., Iyer, R. N., Mehta Steinke, S., Grazia Calvi, E., Tumbarello, M., Falcone, M., Fernandez-Ruiz, M., Costa-Mateo, J. M., Rana, M. M., Mara Varejao Strabelli, T., Paul, M., Carmen Farinas, M., Clemente, W. T., Roilides, E., Munoz, P., Dewispelaere, L., Loeches, B., Lowman, W., Hock Tan, B., Escudero-Sanchez, R., Bodro, M., Antonio Grossi, P., Soldani, F., Gunseren, F., Nestorova, N., Pascual, A., Martinez-Martinez, L., Aguado, J., Rodriguez-Bano, J., Torre-Cisneros, J., Wan Song, A. T., Andraus, W., Carneiro D'Albuquerque, L. A., David-Neto, E., Jota de Paula, F., Rossi, F., Ostrander, D., Avery, R., Rizzi, M., Losito, A. R., Raffaelli, F., Del Giacomo, P., Tiseo, G., Lora-Tamayo, J., San-Juan, R., Gracia-Ahufinger, I., Caston, J., Ruiz, Y. A., Altman, D. R., Campos, S. V., Bar-Sinai, N., Koppel, F., Arnaiz de las Revillas Almajano, F., Gonzalez Rico, C., Fernandez Martinez, M., Mourao, P. H. O., Neves, F. A., Ferreira, J., Pyrpasopoulou, A., Iosifidis, E., Romiopoulos, I., Minero, M. V., Sanchez-Carrillo, C., Lardo, S., Coussement, J., Dodemont, M., Jiayun, K., Martin-Davila, P., Fortun, J., Almela, M., Moreno, A., Linares, L., Gasperina, D. D., Balsamo, M. L., Rovelli, C., Concia, E., Chiesi, S., Salerno, D. N., Ogunc, D., Pilmis, B., Seminari, E. M., Carratala, J., Dominguez, A., Cordero, E., Lepe, J. A., Montejo, M., Merino de Lucas, E., Eriksson, B. M., van Delden, C., Manuel, O., Arslan, H., Kocak Tufan, Z., Kazak, E., David, M., Lease, E., Cornaglia, G., Akova, M., European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Instituto de Salud Carlos III, and Universidad de Cantabria

Subjects
medicine.medical_specialty, Combination therapy, infectious disease, 030230 surgery, Settore MED/17 - MALATTIE INFETTIVE, Logistic regression, clinical research/practice, 03 medical and health sciences, 0302 clinical medicine, infection and infectious agents - bacterial, Internal medicine, medicine, Immunology and Allergy, Pharmacology (medical), organ transplantation in general, Infection and infectious agents - bacterial, Transplantation, Infectious disease, Receiver operating characteristic, business.industry, Hazard ratio, Confidence interval, Organ transplantation in general, antibiotic drug resistance, Cohort, Clinical research/practice, Antibiotic drug resistance, business, Cohort study
Abstract

Treatment of carbapenemase‐producing Enterobacterales bloodstream infections in solid organ transplant recipients is challenging. The objective of this study was to develop a specific score to predict mortality in solid organ transplant recipients with carbapenemase‐producing Enterobacterales bloodstream infections. A multinational, retrospective (2004‐2016) cohort study (INCREMENT‐SOT, ClinicalTrials.gov NCT02852902) was performed. The main outcome variable was 30‐day all‐cause mortality. The INCREMENT‐SOT‐CPE score was developed using logistic regression. The global cohort included 216 patients. The final logistic regression model included the following variables: INCREMENT‐CPE mortality score ≥8 (8 points), no source control (3 points), inappropriate empirical therapy (2 points), cytomegalovirus disease (7 points), lymphopenia (4 points), and the interaction between INCREMENT‐CPE score ≥8 and CMV disease (minus 7 points). This score showed an area under the receiver operating characteristic curve of 0.82 (95% confidence interval [CI] 0.76‐0.88) and classified patients into 3 strata: 0‐7 (low mortality), 8‐11 (high mortality), and 12‐17 (very‐high mortality). We performed a stratified analysis of the effect of monotherapy vs combination therapy among 165 patients who received appropriate therapy. Monotherapy was associated with higher mortality only in the very‐high (adjusted hazard ratio [HR] 2.82, 95% CI 1.13‐7.06, P = .03) and high (HR 9.93, 95% CI 2.08‐47.40, P = .004) mortality risk strata. A score‐based algorithm is provided for therapy guidance., This work 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 RD16/0016/0008; RD16/0016/0001, RD16/0016/0002, RD16/0016/00010] ‐ co‐financed by European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 2014‐2020; ESCMID Study Group for Infections in Compromised Hosts [ESGICH grant to JMA]; Sociedad Andaluza de Trasplante de Órgano Sólido [SATOT grant to LMM]; ESCMID Study Group for Bloodstream Infections and Sepsis (ESGBIS); and ESCMID Study Group for Antimicrobial Resistance Surveillance (ESGARS).

Published
2020

4. Predictors of mortality in solid organ transplant recipients with bloodstream infections due to carbapenemase-producing Enterobacterales: The impact of cytomegalovirus disease and lymphopenia

Author

Perez-Nadales E, Gutierrez-Gutierrez B, Natera A, Abdala E, Magalhaes M, Mularoni A, Monaco F, Pierrotti L, Freire M, Iyer R, Steinke S, Calvi E, Tumbarello M, Falcone M, Fernandez-Ruiz M, Costa-Mateo J, Rana M, Strabelli T, Paul M, Farinas M, Clemente W, Roilides E, Munoz P, Dewispelaere L, Loeches B, Lowman W, Tan B, Escudero-Sanchez R, Bodro M, Grossi P, Soldani F, Gunseren F, Nestorova N, Pascual A, Martinez-Martinez L, Aguado J, Rodriguez-Bano J, Torre-Cisneros J, Song A, Andraus W, D'Albuquerque L, David-Neto E, de Paula F, Rossi F, Ostrander D, Avery R, Rizzi M, Losito A, Raffaelli F, Del Giacomo P, Tiseo G, Lora-Tamayo J, San-Juan R, Gracia-Ahufinger I, Caston J, Ruiz Y, Altman D, Campos S, Bar-Sinai N, Koppel F, Almajano F, Rico C, Martinez M, Mourao P, Neves F, Ferreira J, Pyrpasopoulou A, Iosifidis E, Romiopoulos I, Minero M, Sanchez-Carrillo C, Lardo S, Coussement J, Dodemont M, Jiayun K, Martin-Davila P, Fortun J, Almela M, Moreno A, Linares L, Gasperina D, Balsamo M, Rovelli C, Concia E, Chiesi S, Salerno D, Ogunc D, Pilmis B, Seminari E, Carratala J, Dominguez A, Cordero E, Lepe J, Montejo M, de Lucas E, Eriksson B, van Delden C, Manuel O, Arslan H, Tufan Z, Kazak E, David M, Lease E, Cornaglia G, Akova M, REIPI INCREMENT-SOT Investigators, Swiss Transplant Cohort Study, and ESGARS-ESCMID Study Grp Antimicrob

Subjects
infection and infectious agents - bacterial, clinical research, infectious disease, antibiotic drug resistance, organ transplantation in general, practice
Abstract

Treatment of carbapenemase-producing Enterobacterales bloodstream infections in solid organ transplant recipients is challenging. The objective of this study was to develop a specific score to predict mortality in solid organ transplant recipients with carbapenemase-producing Enterobacterales bloodstream infections. A multinational, retrospective (2004-2016) cohort study (INCREMENT-SOT, ClinicalTrials.gov NCT02852902) was performed. The main outcome variable was 30-day all-cause mortality. The INCREMENT-SOT-CPE score was developed using logistic regression. The global cohort included 216 patients. The final logistic regression model included the following variables: INCREMENT-CPE mortality score >= 8 (8 points), no source control (3 points), inappropriate empirical therapy (2 points), cytomegalovirus disease (7 points), lymphopenia (4 points), and the interaction between INCREMENT-CPE score >= 8 and CMV disease (minus 7 points). This score showed an area under the receiver operating characteristic curve of 0.82 (95% confidence interval [CI] 0.76-0.88) and classified patients into 3 strata: 0-7 (low mortality), 8-11 (high mortality), and 12-17 (very-high mortality). We performed a stratified analysis of the effect of monotherapy vs combination therapy among 165 patients who received appropriate therapy. Monotherapy was associated with higher mortality only in the very-high (adjusted hazard ratio [HR] 2.82, 95% CI 1.13-7.06, P = .03) and high (HR 9.93, 95% CI 2.08-47.40, P = .004) mortality risk strata. A score-based algorithm is provided for therapy guidance.

Published
2020

5. Perspectives on Scedosporium species and Lomentospora prolificans in lung transplantation: Results of an international practice survey from ESCMID fungal infection study group and study group for infections in compromised hosts, and European Confederation of Medical Mycology

Author

Rammaert, B., Puyade, M., Cornely, O. A., Seidel, D., Grossi, P., Husain, S., Picard, C., Lass-Florl, C., Manuel, O., Le Pavec, J., Lortholary, O., Nagel, C., Westall, G., Morrissey, O., Chambers, D., Eschertzhuber, S., Coussement, J., Knoop, C., Vos, R., Dupont, L., Dumonceaux, M., Campos, S. V., Kabbani, D., Cervera, C., Luong, M. -L., Blanchard, E., Senechal, A., Pavec, J. L., Brugiere, O., Boussaud, V., Guillemain, R., Bervar, J. -F., Claustre, J., Haloun, A., Hirschi, S., Reynaud, M., Kneidinger, N., Gottlieb, J., Roilides, E., Zarrinfar, H., Rosso, L., Morlacchi, L. C., Dell'Amore, A., Loy, M., Santos, C. O. D., Rello, J., Monforte, V., Martin-Gomez, M. T., Medrano, F. L., Fernandez-Ruiz, M., Sole, A., Cifrian, J. M., Neofytos, D., Mueller, N., Benden, C., Brill, A. K., Kiyan, E., Gould, K., Gkrania-Klotsas, E., David, M., Weigt, S., Kwak, E. J., Silveira, F., Hadjiliadis, D., Baddley, J., Danziger-Isakov, L., Bhorade, S., Ison, M., Wolfe, C., Aslam, S., Budem, M., Musetti, A., Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), University Hospital of Cologne [Cologne], Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases - CECAD [Cologne, Germany] (Institute for Genetics), University of Cologne, German Centre for Infection Research (DZIF), Universitá degli Studi dell’Insubria = University of Insubria [Varese] (Uninsubria), University Health Network, Hôpital Foch [Suresnes], Leopold Franzens Universität Innsbruck - University of Innsbruck, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Centre Chirurgical Marie Lannelongue (CCML), Hypertension arterielle pulmonaire physiopathologie et innovation thérapeutique, Centre Chirurgical Marie Lannelongue (CCML)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11), Université Paris-Saclay, Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence Mycologie et Antifongiques-Mycologie Moléculaire (CNRMA), Institut Pasteur [Paris] (IP), The authors thank all the people who helped to collect mycological data and to contact transplant centers: Alejandro Mario Bertolotti (Buenos Aires, Argentina), Claire Heney (Brisbane, Australia), Carlota Montesinos (Brussels, Belgium), Katrien Lagrou (Leuven, Belgium), Youri Gluczynski (Yvoir, Belgium), Sandrine Houze (Paris, France), Eric Dannaoui (Paris, France), Florent Morio (Nantes, France), Murielle Cornet (Grenoble, France), Valérie Bru (Strasbourg, France), Stéphane Ranque (Marseille, France), Emilie Cardot (Suresnes, France), Ludwig Sedlacek (Hannover, Germany), Maurizio Sanguinetti (Roma, Italy), Ana Alastruey (Madrid, Spain), Konrad Muehlethaler (Bern, Switzerland), Kevin Alby (Philadelphia, USA), Malcom Richardson (Manchester, UK), the members of the ESCMID Fungal Infection Study Group (EFISG) and Study Group for Infections in Compromised Hosts (ESGICH) and European Confederation of Medical Mycology (ECMM) who helped to promote the study, Jeffrey Arsham for editing our original English language manuscript., The SCEDO‐LUNG collaborative group collected the data., University of Insubria, Varese, University of Innsbruck, Centre chirurgical Marie Lannelongue, Centre chirurgical Marie Lannelongue-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris]

Subjects
Internationality, [SDV]Life Sciences [q-bio], invasive fungal disease, lomentosporiosis, scedosporiosis, solid organ transplantation, Ascomycota, Humans, Lung Transplantation, Mycoses, Prospective Studies, Respiratory Tract Infections, Scedosporium, Surveys and Questionnaires, Disease Management, Immunocompromised Host, MESH: Mycoses/epidemiology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Mycoses/etiology, MESH: Surveys and Questionnaires, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, MESH: Respiratory Tract Infections/etiology, MESH: Humans, MESH: Respiratory Tract Infections/microbiology, MESH: Scedosporium/isolation & purification, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, MESH: Lung Transplantation/adverse effects, MESH: Prospective Studies, MESH: Disease Management, MESH: Internationality, MESH: Ascomycota/isolation & purification, MESH: Immunocompromised Host
Abstract

International audience; Background: Scedosporium species and Lomentospora prolificans (S/L) are the second most common causes of invasive mold infections following Aspergillus in lung transplant recipients.Methods: We assessed the current practices on management of S/L colonization/infection of the lower respiratory tract before and after lung transplantation in a large number of lung transplant centers through an international practice survey from October 2016 to March 2017.Results: A total of 51 respondents from 45 lung transplant centers (17 countries, 4 continents) answered the survey (response rate 58%). S/L colonization was estimated to be detected in candidates by 48% of centers. Only 18% of the centers used a specific medium to detect S/L colonization. Scedosporium spp. colonization was a contraindication to transplantation in 10% of centers whereas L prolificans was a contraindication in 31%; 22% of centers declared having had 1-5 recipients infected with S/L in the past 5 years.Conclusions: This survey gives an overview of the current practices regarding S/L colonization and infection in lung transplant centers worldwide and underscores the need of S/L culture procedure standardization before implementing prospective studies.

Published
2019

6. 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

7. Nocardia Infection in Solid Organ Transplant Recipients: A Multicenter European Case-control Study

Author

Coussement, J., Lebeaux, D., Delden, C. van, Guillot, H., Freund, R., Marbus, S., Melica, G., Wijngaerden, E. van, Douvry, B., Laecke, S. van, Vuotto, F., Tricot, L., Fernandez-Ruiz, M., Dantal, J., Hirzel, C., Jais, J.P., Rodriguez-Nava, V., Lortholary, O., Jacobs, F., European Study Grp Nocardia Solid, Department Infections Diseases, Université Libre de Bruxelles [Bruxelles] (ULB), Centre Infectiologie, CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Transplantation Infection Disease Unity, Hôpitaux Universitaires de Genève (HUG), Swiss Transplant Cohort Study, University of Basel (Unibas), Service Maladies Infectieuses et Tropicales, Hôpital Universitaire Pitié Salpêtrière, Assistance Publique - Hôpitaux de Paris (AP - HP), Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Biostatistique, Centre Hospitalier Universitaire de Clermont-Ferrand, Medical Center, Department of Infectious Diseases, Leiden University, Immunologie Clinique et Maladies Infectieuses, Hopital Henri Mondor (APHP), Département Génétique Internal Médecine, Hôpital Universitaire Leuven, Service Pneumologie et Transplantation Pulmonaire, Hôpital Foch [Suresnes], Renal Division, Freiburg University Medical Center, Unité Maladies Infectieuses, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service Néphrologie Transplantation Rénale, Unit Infectious Diseases, Hospital 12 de Octubre, Institut Transplantation Urologie et Néphrologie, Centre hospitalier universitaire de Nantes (CHU Nantes), Swiss Transplantation Cohort Study, Department Infectious Diseases, University Hospital of Bern, Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Lyon (ENVL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Centrer Infectiologie, Department of Infectious Diseases, University of Gothenburg (GU), Societe de Pathologie Infectieuse de Langue Francaise, Prix Fonds Carine Vyghen pour le don d'organes, Swiss National Science Foundation, Swiss University Hospitals (G15) and transplant centers, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université libre de Bruxelles (ULB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Clermont-Ferrand, Universiteit Leiden, Hôpital Henri Mondor, Universitäts Klinikum Freiburg = University Medical Center Freiburg (Uniklinik), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Ecole Nationale Vétérinaire de Lyon (ENVL), Université Libre de Bruxelles [Bruxelles] ( ULB ), Hôpital Necker-Enfants Malades, Assistance Publique - Hôpitaux de Paris ( AP-HP ), Institut Imagine, Hôpitaux Universitaires de Genève ( HUG ), University of Basel ( Unibas ), Hôpital Universitaire Pitié Salpêtrière, Assistance Publique - Hôpitaux de Paris ( AP - HP ), Centre de Recherche des Cordeliers ( CRC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -École pratique des hautes études ( EPHE ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hopital Henri Mondor ( APHP ), Centre Hospitalier Régional Universitaire de Lille ( CHRU de Lille ), Centre Hospitalier Universitaire de Nantes, Ecologie microbienne ( EM ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Vétérinaire de Lyon ( ENVL ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique ( INRA ) -VetAgro Sup ( VAS ), and University of Gothenburg ( GU )

Subjects
Male, 0301 basic medicine, Opportunistic infection, opportunistic infection, greffe d'organe, Transplants, organ transplant, Organ transplantation, Nocardia, Risk Factors, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Medicine, ddc:616, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, ddc:618, [ SDV.MHEP.ME ] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, biology, Nocardiosis, Middle Aged, opportunistic infections, 3. Good health, Europe, Infectious Diseases, nocardiaceae, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Nocardia Infections, Adult, Microbiology (medical), medicine.medical_specialty, Calcineurin Inhibitors, 030106 microbiology, 610 Medicine & health, 03 medical and health sciences, Internal medicine, Trimethoprim, Sulfamethoxazole Drug Combination, Humans, Intensive care medicine, Aged, Retrospective Studies, nocardiosis, business.industry, Retrospective cohort study, biology.organism_classification, medicine.disease, Transplant Recipients, infection, Tacrolimus, Transplantation, Logistic Models, Case-Control Studies, business
Abstract

Background. Nocardiosis is a rare, life-threatening opportunistic infection, affecting 0.04% to 3.5% of patients after solid organ transplant (SOT). The aim of this study was to identify risk factors for Nocardia infection after SOT and to describe the presentation of nocardiosis in these patients.Methods. We performed a retrospective case-control study of adult patients diagnosed with nocardiosis after SOT between 2000 and 2014 in 36 European (France, Belgium, Switzerland, the Netherlands, Spain) centers. Two control subjects per case were matched by institution, transplant date, and transplanted organ. A multivariable analysis was performed using conditional logistic regression to identify risk factors for nocardiosis.Results. One hundred and seventeen cases of nocardiosis and 234 control patients were included. Nocardiosis occurred at a median of 17.5 (range, 2-244) months after transplant. In multivariable analysis, high calcineurin inhibitor trough levels in the month before diagnosis (odds ratio [OR], 6.11; 95% confidence interval [CI], 2.58-14.51), use of tacrolimus (OR, 2.65; 95% CI, 1.17-6.00) and corticosteroid dose (OR, 1.12; 95% CI, 1.03-1.22) at the time of diagnosis, patient age (OR, 1.04; 95% CI, 1.02-1.07), and length of stay in the intensive care unit after SOT (OR, 1.04; 95% CI, 1.00-1.09) were independently associated with development of nocardiosis; low-dose cotrimoxazole prophylaxis was not found to prevent nocardiosis. Nocardia farcinica was more frequently associated with brain, skin, and subcutaneous tissue infections than were other Nocardia species. Among the 30 cases with central nervous system nocardiosis, 13 (43.3%) had no neurological symptoms.Conclusions. We identified 5 risk factors for nocardiosis after SOT. Low-dose cotrimoxazole was not found to prevent Nocardia infection. These findings may help improve management of transplant recipients.

Published
2016

8. 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

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

Author

Lopez-Medrano, F, Silva, JT, Fernandez-Ruiz, M, Carver, PL, van Delden, C, Merino, E, Perez-Saez, MJ, Montero, M, Coussement, J, de Abreu Mazzolin, M, Cervera, C, Santos, L, Sabe, N, Scemla, A, Cordero, E, Cruzado-Vega, L, Martin-Moreno, PL, Len, O, Rudas, E, de Leon, AP, Arriola, M, Lauzurica, R, David, M, Gonzalez-Rico, C, Henriquez-Palop, F, Fortun, J, Nucci, M, Manuel, O, Pano-Pardo, JR, Montejo, M, Munoz, P, Sanchez-Sobrino, B, Mazuecos, A, Pascual, J, Horcajada, JP, Lecompte, T, Lumbreras, C, Moreno, A, Carratala, J, Blanes, M, Hernandez, D, Hernandez-Mendez, EA, Farinas, MC, Perello-Carrascosa, M, Morales, JM, Andres, A, Aguado, JM, Spanish Network Res Infect Dis, Spanish Soc Clinical Microbiology, European Soc Clinical Microbiology, and Swiss Transplant Cohort Study STCS

Subjects
infection and infectious agents, clinical research, infectious disease, fungal, nephrology, kidney transplantation, epidemiology, practice
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

10. Multiple Wilson and Jacobi-Pineiro polynomials

Author

Beckermann, B., Coussement, J., and Van Assche, W.

Subjects
Mathematics - Classical Analysis and ODEs, Classical Analysis and ODEs (math.CA), FOS: Mathematics, Mathematics::Classical Analysis and ODEs, 33C45, 42C05
Abstract

We introduce multiple Wilson polynomials, which give a new example of multiple orthogonal polynomials (Hermite-Pade polynomials) of type II. These polynomials can be written as a Jacobi-Pineiro transform, which is a generalization of the Jacobi transform for Wilson polynomials, found by T.H. Koornwinder. Here we need to introduce Jacobi and Jacobi-Pineiro polynomials with complex parameters. Some explicit formulas are provided for both Jacobi-Pineiro and multiple Wilson polynomials, one of them in terms of Kampe de Feriet series. Finally we look at some limiting relations and construct a part of a multiple AT-Askey table., 22 pages, 2 figures

Published
2003

11. Valpreventie bij thuiswonende ouderen. Praktijkrichtlijn voor Vlaanderen

Author

Milisen, K., Coussement, J., Vlaeyen, E., Ivan Bautmans, Bertrand, I., Boonen, S., Dirk Cambier, Coninck, L., Cuyper, M., Gerontologie, and Fragiliteit binnen Gerontologie en Geriatrie

Subjects
fall, Prevention, elderly, guideline
Abstract

Verschillende bestaande richtlijnen en initiatieven rond valpreventie bij thuiswonende ouderen in Vlaanderen werden in opdracht van Vlaams minister van Welzijn, Volksgezondheid en Gezin samengevoegd tot een uniforme richtlijn (zie historiek). Tegelijkertijd werd een update voorzien op basis van nieuwe bevindingen uit de literatuur. Vanaf heden wordt de omschrijving "uniforme richtlijn valpreventie Vlaanderen" vervangen door "praktijkrichtlijn valpreventie voor Vlaanderen". Iedere oudere is immers uniek: hoewel valpreventie om een zekere structuur vraagt, hoeft de aanpak niet noodzakelijk uniform te zijn voor alle ouderen.

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