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.