Piperacillin/tazobactam vs. cefepime or carbapenems for the treatment of bloodstream infections due to bacteria producing chromosomal AmpC beta-lactamase: a systematic review and meta-analysis

Background: The best treatment for bloodstream infections (BSI) due to chromosomal AmpC (c-AmpC) producing Enterobacterales is not clearly defined.

Objectives: 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.

Data sources: We searched MEDLINE, the Cochrane Library and EMBASE to screen original reports published up to January 2024.

Study eligibility criteria: 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.

Participants: Patients with bloodstream infections due to c-AmpC producing bacteria.

Interventions: Piperacillin/tazobactam, cefepime or carbapenems as targeted treatment.

Assessment of risk of bias: We used the Cochrane Risk of Bias Tool for RCTs, and the Newcastle Ottawa scale for observational studies.

Methods of data synthesis: We conducted a meta-analysis pooling Risk ratios (RRs) through random effect models.

Results: 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).

Conclusions: 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.