Abstract

The best treatment for bloodstream infections (BSI) due to chromosomal AmpC (c-AmpC) producing Enterobacterales is not clearly defined. To describe the clinical and microbiological outcomes of patients treated with piperacillin/tazobactam, cefepime or carbapenems for bloodstream infections (BSIs) due to c-AmpC beta-lactamase-producing strains. We searched MEDLINE, the Cochrane Library and EMBASE to screen original reports published up to January 2024. RCTs and observational studies investigating all-cause mortality, clinical failure, microbiological failure or rate of ADRs of patients treated with piperacillin/tazobactam, cefepime or carbapenems. Patients with bloodstream infections due to c-AmpC producing bacteria. Piperacillin/tazobactam, cefepime or carbapenems as targeted treatment. We used the Cochrane Risk of Bias Tool for RCTs, and the Newcastle Ottawa scale for observational studies. We conducted a meta-analysis pooling Risk ratios (RRs) through random effect models. We screened 1,720 original reports, and 20 studies (1 RCTs, 1 case-control study, 18 cohort studies) were included in the analysis, for a total of 2,834 patients. When comparing piperacillin/tazobactam with alternative treatments (cefepime or carbapenems), no significant difference in mortality rate was observed between the treatment groups (RR: 1.1; 95% CI: 0.76-1.58, p = 0.61), while an higher rate of microbiological failure (RR: 1.80; 95% CI: 1.15-2.82, p = 0.01) and clinical failure (RR: 1.54; 95% CI: 1.00-2.40, p = 0.05) was observed among patients receiving piperacillin/tazobactam. No difference was observed in microbiological and clinical failure rate among patients treated with cefepime or carbapenems, with a lower mortality rate in those receiving cefepime (RR: 0.74; 95% CI: 0.59-0.94, p = 0.014). Cefepime represents an excellent alternative to carbapenems for BSI due to AmpC-producing strains, whereas piperacillin/tazobactam is associated with a higher rate of clinical and microbiological failure. There is an urgent need for randomized clinical trials that aim to define the best carbapenem-sparing strategy in these infections.

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