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

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. 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. 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. 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.