Ligia C Pierrotti1, Elena Pérez-Nadales2,3, Mario Fernández-Ruiz2,4, Belén Gutiérrez-Gutiérrez2,5, Ban Hock Tan6, Jordi Carratalà2,7, Isabel Oriol2,7, Mical Paul8, Noa Cohen-Sinai9, Francisco López-Medrano2,4, Rafael San-Juan2,4, Miguel Montejo10, Maristela P Freire11, Elisa Cordero2,12, Miruna D David13, Esperanza Merino14, Seema Mehta Steinke15, Paolo A Grossi16, Ángela Cano2,5, Elena M Seminari17, Maricela Valerio18, Filiz Gunseren19, Meenakshi Rana20, Alessandra Mularoni21, Pilar Martín-Dávila2,22, Christian van Delden23, Melike Hamiyet Demirkaya24, Zeliha Koçak Tufan25, Belén Loeches26, Ranganathan N Iyer27, Fabio Soldani28, Britt-Marie Eriksson29, Benoît Pilmis30, Marco Rizzi31, Julien Coussement32, Wanessa T Clemente33, Emmanuel Roilides34, Álvaro Pascual2,5, Luis Martínez-Martínez2,35, Jesús Rodríguez-Baño2,5, Julian Torre-Cisneros2,36, José María Aguado2,4. 1. Infectious Diseases Division, Hospital das Clínicas, University of São Paulo Medical School, São Paulo, Brazil. 2. Spanish Network for Research in Infectious Diseases (REIPI), ISCIII, Madrid, Spain. 3. Infectious Diseases Group, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofía University Hospital, University of Cordoba, Cordoba, Spain. 4. Unit of Infectious Diseases, "12 de Octubre" University Hospital, Instituto de Investigación Sanitaria Hospital "12 de Octubre" (imas12), Universidad Complutense, Madrid, Spain. 5. Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Virgen Macarena University Hospital, Institute of Biomedicine of Seville, University of Seville, Seville, Spain. 6. Department of Infectious Diseases, Singapore General Hospital, Singapore. 7. Department of Infectious Diseases, Bellvitge University Hospital-IDIBELL, University of Barcelona, L´Hospitalet de Llobregat, Barcelona, Spain. 8. Infectious Diseases Institute, Rambam Health Care Campus, Haifa, Israel. 9. Technion - Israel Institute of Technology, Haifa, Israel. 10. Infectious Diseases Unit, Cruces University Hospital, Bilbao, Spain. 11. Working Committee for Hospital Epidemiology and Infection Control, Hospital das Clínicas, University of São Paulo Medical School, São Paulo, Brazil. 12. Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville, University Hospitals Virgen del Rocío/CSIC/University of Seville, Seville, Spain. 13. University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom. 14. Unit of Infectious Diseases, General University Hospital of Alicante, ISABIAL, Alicante, Spain. 15. School of Medicine, Johns Hopkins University, Baltimore, USA. 16. Department of Medicine and Surgery, University of Insubria, Varese, Italy. 17. Infectious Diseases Clinic, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy. 18. Clinical Microbiology and Infectious Disease Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain. 19. Department of Infectious Diseases and Clinical Microbiology, Akdeniz University Faculty of Medicine, Antalya, Turkey. 20. Icahn School of Medicine at Mount Sinai, New York, USA. 21. IRCCS-ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione), Palermo, Italy. 22. Infectious Diseases Department, Ramón y Cajal University Hospital, Madrid, Spain. 23. Unit for Transplant Infectious Diseases, University Hospitals of Geneva, Geneva, Switzerland. 24. Başkent University School of Medicine, Ankara, Turkey. 25. Infectious Diseases and Clinical Microbiology Department, Medical School of Ankara Yildirim Beyazit University, Ankara, Turkey. 26. Infectious Diseases Unit, Hospital Universitario La Paz, IdiPAZ, Madrid, Spain. 27. Clinical Microbiology ID & Infection control, Global Hospitals, Hyderabad, India. 28. Division of Infectious Diseases, Department of Medicine, Azienda Ospedaliera Universitaria Integrata di Verona, Verona, Italy. 29. Department of Medical Sciences, Section of Infectious Diseases, Uppsala University, Uppsala, Sweden. 30. Department of Infectious Diseases and Tropical Medicine, Paris Descartes University, Necker-Enfants Malades University Hospital, Centre d'Infectiologie Necker-Pasteur, Institut Imagine, AP-HP, Paris, France. 31. Infectious Diseases Unit, ASST Papa Giovanni XXIII, Bergamo, Italy. 32. Division of Infectious Diseases, CUB-Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium. 33. Faculdade de Medicina da Universidade Federal de Minas Gerais (UFMG), Transplant Infectious Disease, Liver Transplant Program, Hospital das Clínicas da UFMG, Belo Horizonte, Brazil. 34. Infectious Diseases Unit and 3rd Department of Pediatrics, Aristotle University School of Health Sciences, Hippokration Hospital, Thessaloniki, Greece. 35. Clinical Unit of Microbiology, Department of Microbiology, Reina Sofía University Hospital, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, Córdoba, Spain. 36. Clinical Unit of Infectious Diseases, Reina Sofía University Hospital, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, Córdoba, Spain.
Abstract
BACKGROUND: Whether active therapy with β-lactam/β-lactamase inhibitors (BLBLI) is as affective as carbapenems for extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) bloodstream infection (BSI) secondary to urinary tract infection (UTI) in kidney transplant recipients (KTRs) remains unclear. METHODS: We retrospectively evaluated 306 KTR admitted to 30 centers from January 2014 to October 2016. Therapeutic failure (lack of cure or clinical improvement and/or death from any cause) at days 7 and 30 from ESBL-E BSI onset was the primary and secondary study outcomes, respectively. RESULTS: Therapeutic failure at days 7 and 30 occurred in 8.2% (25/306) and 13.4% (41/306) of patients. Hospital-acquired BSI (adjusted OR [aOR]: 4.10; 95% confidence interval [CI]: 1.50-11.20) and Pitt score (aOR: 1.47; 95% CI: 1.21-1.77) were independently associated with therapeutic failure at day 7. Age-adjusted Charlson Index (aOR: 1.25; 95% CI: 1.05-1.48), Pitt score (aOR: 1.72; 95% CI: 1.35-2.17), and lymphocyte count ≤500 cells/μL at presentation (aOR: 3.16; 95% CI: 1.42-7.06) predicted therapeutic failure at day 30. Carbapenem monotherapy (68.6%, primarily meropenem) was the most frequent active therapy, followed by BLBLI monotherapy (10.8%, mostly piperacillin-tazobactam). Propensity score (PS)-adjusted models revealed no significant impact of the choice of active therapy (carbapenem-containing vs any other regimen, BLBLI- vs carbapenem-based monotherapy) within the first 72 hours on any of the study outcomes. CONCLUSIONS: Our data suggest that active therapy based on BLBLI may be as effective as carbapenem-containing regimens for ESBL-E BSI secondary to UTI in the specific population of KTR. Potential residual confounding and unpowered sample size cannot be excluded (ClinicalTrials.gov identifier: NCT02852902).
BACKGROUND: Whether active therapy with β-lactam/β-lactamase inhibitors (BLBLI) is as affective as carbapenems for extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) bloodstream infection (BSI) secondary to urinary tract infection (UTI) in kidney transplant recipients (KTRs) remains unclear. METHODS: We retrospectively evaluated 306 KTR admitted to 30 centers from January 2014 to October 2016. Therapeutic failure (lack of cure or clinical improvement and/or death from any cause) at days 7 and 30 from ESBL-E BSI onset was the primary and secondary study outcomes, respectively. RESULTS: Therapeutic failure at days 7 and 30 occurred in 8.2% (25/306) and 13.4% (41/306) of patients. Hospital-acquired BSI (adjusted OR [aOR]: 4.10; 95% confidence interval [CI]: 1.50-11.20) and Pitt score (aOR: 1.47; 95% CI: 1.21-1.77) were independently associated with therapeutic failure at day 7. Age-adjusted Charlson Index (aOR: 1.25; 95% CI: 1.05-1.48), Pitt score (aOR: 1.72; 95% CI: 1.35-2.17), and lymphocyte count ≤500 cells/μL at presentation (aOR: 3.16; 95% CI: 1.42-7.06) predicted therapeutic failure at day 30. Carbapenem monotherapy (68.6%, primarily meropenem) was the most frequent active therapy, followed by BLBLI monotherapy (10.8%, mostly piperacillin-tazobactam). Propensity score (PS)-adjusted models revealed no significant impact of the choice of active therapy (carbapenem-containing vs any other regimen, BLBLI- vs carbapenem-based monotherapy) within the first 72 hours on any of the study outcomes. CONCLUSIONS: Our data suggest that active therapy based on BLBLI may be as effective as carbapenem-containing regimens for ESBL-E BSI secondary to UTI in the specific population of KTR. Potential residual confounding and unpowered sample size cannot be excluded (ClinicalTrials.gov identifier: NCT02852902).
Authors: Elena Pérez-Nadales; Mario Fernández-Ruiz; Belén Gutiérrez-Gutiérrez; Álvaro Pascual; Jesús Rodríguez-Baño; Luis Martínez-Martínez; José María Aguado; Julian Torre-Cisneros Journal: Transpl Infect Dis Date: 2022-06-28