Beta-lactam/beta-lactamase inhibitors versus carbapenem for bloodstream infections due to extended-spectrum beta-lactamase-producing Enterobacteriaceae: systematic review and meta-analysis

Background: Infections due to extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae pose a major public health threat due to poor outcomes and high mortality rates. A systematic review and meta-analysis was conducted to investigate the impact of intravenous beta-lactam/beta-lactamase inhibitors (BL-BLI), including piperacillin-tazobactam (PTZ), on mortality of participants with ESBL-producing Enterobacteriaceae bloodstream infections compared with carbapenem. Methods: MEDLINE, EMBASE, and the Cochrane library were electronically searched for studies through June 15, 2017 that have provided data for mortality and addressed the terms ESBL and PTZ or BL-BLI and carbapenem. Data extraction on study design, characteristics of the population, intervention, comparator, and outcomes was performed. A meta-analysis with a random-effects model was performed. Results: A total of 25 observational studies describing 3842 participants were included and analyzed. Within 30-day mortality of BL-BLI or PTZ for ESBL-producing Enterobacteriaceae bloodstream infections treatment was not statistically different from carbapenem (pooled odds ratios (OR): 1.07, 95% CI 0.81; 1.82 and 1.18, 95% CI 0.93; 1.5, respectively). No statistically significant differences in mortality were found between BL-BLI or PTZ and carbapenem administered as definitive (OR: 0.96, 95% CI 0.59; 1.86 and 0.97, 95% CI 0.59; 1.6, respectively) or empirical (OR 1.13, 95% CI 0.87; 1.48 and 1.27, 95% CI 0.96; 1.66) treatment. Conclusions: These findings suggest that there is no significant difference in 30-day mortality between BL-BLI, including PTZ and carbapenems, in treating ESBL-producing Enterobacteriaceae bloodstream infections. Moreover, intravenous BL-BLI, especially PTZ, may be considered as an alternative treatment for ESBL-producing Enterobacteriaceae bloodstream infections. Future studies are needed to validate these findings. (c) 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.