A Multinational, Preregistered Cohort Study of beta-Lactam/beta-Lactamase Inhibitor Combinations for Treatment of Bloodstream Infections Due to Extended-Spectrum-beta-Lactamase-Producing Enterobacteriaceae

Gutierrez-Gutierrez, Belen; Perez-Galera, Salvador; Salamanca, Elena; de Cueto, Marina; Calbo, Esther; Almirante, Benito; Viale, Pierluigi; Oliver, Antonio; Pintado, Vicente; Gasch, Oriol; Martinez-Martinez, Luis; Pitout, Johann; Akova, Murat; Pena, Carmen; Molina, Jose; Hernandez, Alicia; Venditti, Mario; Prim, Nuria; Origuen, Julia; Bou, German; Tacconelli, Evelina; Tumbarello, Mario; Hamprecht, Axel; Giamarellou, Helen; Almela, Manel; Perez, Federico; Schwaber, Mitchell J.; Bermejo, Joaquin; Lowman, Warren; Hsueh, Po-Ren; Mora-Rillo, Marta; Natera, Clara; Souli, Maria; Bonomo, Robert A.; Carmeli, Yehuda; Paterson, David L.; Pascual, Alvaro; Rodriguez-Bano, Jesus; REIPI ESGBIS INCREMENT Grp

doi:10.1128/AAC.00365-16

Identifier to cite or link to this item: http://hdl.handle.net/20.500.13003/10288

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Antimicrobial_Agents_Chemotherapy-2016-60-7.pdf (811.2Kb)

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URI: http://hdl.handle.net/20.500.13003/10288

DOI: 10.1128/AAC.00365-16

ISSN: 0066-4804

eISSN: 1098-6596

WOS ID: 000378094400034

Scopus EID: 2-s2.0-84977072761

PMID: 27139473

Embase PUI: L611027865

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2016-07

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research article

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Gutierrez-Gutierrez Belen, Perez-Galera Salvador, Salamanca Elena, De Cueto Marina, Calbo Esther, Almirante Benito, et al. A Multinational, Preregistered Cohort Study of beta-Lactam/beta-Lactamase Inhibitor Combinations for Treatment of Bloodstream Infections Due to Extended-Spectrum-beta-Lactamase-Producing Enterobacteriaceae. Antimicrob Agents Chemother. 2016 Jul;60(7):4159-4169.

Abstract

The spread of extended-spectrum-beta-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) is leading to increased carbapenem consumption. Alternatives to carbapenems need to be investigated. We investigated whether beta-lactam/beta-lactamase inhibitor (BLBLI) combinations are as effective as carbapenems in the treatment of bloodstream infections (BSI) due to ESBL-E. A multinational, retrospective cohort study was performed. Patients with monomicrobial BSI due to ESBL-E were studied; specific criteria were applied for inclusion of patients in the empirical-therapy (ET) cohort (ETC; 365 patients), targeted-therapy (TT) cohort (TTC; 601 patients), and global cohort (GC; 627 patients). The main outcome variables were cure/improvement rate at day 14 and all-cause 30-day mortality. Multivariate analysis, propensity scores (PS), and sensitivity analyses were used to control for confounding. The cure/improvement rates with BLBLIs and carbapenems were 80.0% and 78.9% in the ETC and 90.2% and 85.5% in the TTC, respectively. The 30-day mortality rates were 17.6% and 20% in the ETC and 9.8% and 13.9% in the TTC, respectively. The adjusted odds ratio (OR) (95% confidence interval [CI]) values for cure/improvement rate with ET with BLBLIs were 1.37 (0.69 to 2.76); for TT, they were 1.61 (0.58 to 4.86). Regarding 30-day mortality, the adjusted OR (95% CI) values were 0.55 (0.25 to 1.18) for ET and 0.59 (0.19 to 1.71) for TT. The results were consistent in all subgroups studied, in a stratified analysis according to quartiles of PS, in PS-matched cases, and in the GC. BLBLIs, if active in vitro, appear to be as effective as carbapenems for ET and TT of BSI due to ESLB-E regardless of the source and specific species. These data may help to avoid the overuse of carbapenems. (This study has been registered at ClinicalTrials.gov under registration no. NCT01764490.)