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).

Efficacy of β-lactam/β-lactamase inhibitors to treat extended-spectrum beta-lactamase-producing Enterobacterales bacteremia secondary to urinary tract infection in kidney transplant recipients (INCREMENT-SOT Project)

Grossi P. A.
Membro del Collaboration Group
;
Dalla Gasperina D.;Rovelli C.;Leoni C.;Falcone M.;
2020-01-01

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).
2020
2020
bloodstream infection; carbapenem-sparing regimen; extended-spectrum β-lactamase-producing Enterobacterales; kidney transplantation; outcomes; urinary tract infection; Anti-Bacterial Agents; Carbapenems; Enterobacteriaceae Infections; Humans; Lactams; Retrospective Studies; beta-Lactamase Inhibitors; beta-Lactamases; Bacteremia; Kidney Transplantation; Urinary Tract Infections
Pierrotti, L. C.; Perez-Nadales, E.; Fernandez-Ruiz, M.; Gutierrez-Gutierrez, B.; Hock Tan, B.; Carratala, J.; Oriol, I.; Paul, M.; Cohen-Sinai, N.; Lopez-Medrano, F.; San-Juan, R.; Montejo, M.; Freire, M. P.; Cordero, E.; David, M. D.; Merino, E.; Mehta Steinke, S.; Grossi, P. A.; Cano, A.; Seminari, E. M.; Valerio, M.; Gunseren, F.; Rana, M.; Mularoni, A.; Martin-Davila, P.; van Delden, C.; Hamiyet Demirkaya, M.; Kocak Tufan, Z.; Loeches, B.; Iyer, R. N.; Soldani, F.; Eriksson, B. -M.; Pilmis, B.; Rizzi, M.; Coussement, J.; Clemente, W. T.; Roilides, E.; Pascual, A.; Martinez-Martinez, L.; Rodriguez-Bano, J.; Torre-Cisneros, J.; Maria Aguado, J.; Kee, T. Y. S.; Sabe, N.; Camoez, M.; Dominguez, M. A.; Koppel, F.; Lora-Tamayo, J.; Lopez-Soria, L.; David-Neto, E.; de Paula e Flavia Rossi, F. J.; Lepe, J. A.; Blanco, G. B.; Martin-Gandul, C.; Balibrea, N.; Franco, A.; Avery, R.; Ostrander, D.; Dalla Gasperina, D.; Rovelli, C.; Natera, A. M.; Recio-Rufian, M.; Guzman-Puche, J.; Leoni, C.; Munoz, P.; Sanchez-Carrillo, C.; Lardo, S.; Altman, D. R.; Fortun, J.; Escudero, R.; Gioia, F.; Muller, N. J.; Manuel, O.; Arslan, H.; Hasanoglu, I.; Lopez Oliva, M.; Chiese, S.; Salerno, N. D.; Lortholary, O.; Scemla, A.; Grazia Calvi, E.; Dewispelaere, L.; Mourao, P. H. O.; Pyrpasopoulou, A.; Romiopoulos, I.; Iosifidis, E.; Abdala, E.; Bodro, M.; Strabelli, T. M. V.; Farinas, M. C.; Lowman, W.; Falcone, M.; Kazak, E.; Tumbarello, M.; Lease, E.; Nestorova, N.
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