Meropenem Versus Piperacillin-Tazobactam for Definitive Treatment of Bloodstream Infections Caused by AmpC β-Lactamase–Producing Enterobacter spp, Citrobacter freundii, Morganella morganii, Providencia spp, or Serratia marcescens: A Pilot Multicenter Randomized Controlled Trial (MERINO-2)

Abstract

Background Carbapenems are recommended treatment for serious infections caused AmpC-producing gram-negative bacteria but can select for carbapenem resistance. Piperacillin-tazobactam may be a suitable alternative. Methods We enrolled adult patients with bloodstream infection due to chromosomal AmpC-producers in a multicenter randomized controlled trial. Patients were assigned 1:1 to receive piperacillin-tazobactam 4.5 g every 6 hours or meropenem 1 g every 8 hours. The primary efficacy outcome was a composite of death, clinical failure, microbiological failure and microbiological relapse at 30 days. Results Seventy-two patients underwent randomization and were included in the primary analysis population. 11 of 38 patients (29%) randomized to piperacillin-tazobactam met the primary outcome compared with 7 of 34 patients (21%) in the meropenem group (risk difference, 8%, [95% CI –12% to 28%]). Effects were consistent in an analysis of the per-protocol population. Within the subcomponents of the primary outcome, 5 of 38 (13%) experienced microbiological failure in the piperacillin-tazobactam group compared to 0 of 34 patients (0%) in the meropenem group (risk difference, 13% [95% CI 2% to 24%]). In contrast, 0% versus 9% of microbiological relapses were seen in the piperacillin-tazobactam and meropenem arms, respectively. 96.5% and 100% were susceptible to piperacillin-tazobactam and meropenem, respectively using broth microdilution. The most common AmpC beta-lactamase genes identified were blaCMY-2, blaDHA-17, blaCMH-3 and blaACT-17. No ESBL, OXA or other carbapenemase genes were identified. Conclusion Among patients with bloodstream infection due to AmpC-producers, piperacillin-tazobactam may lead to more microbiological failures, although less microbiological relapses were seen.

An Antimicrobial Treatment Assessment of Serratia marcescens Bacteremia and Endocarditis

“…Use of piperacillin-tazobactam as a carbapenem-avoidance strategy has been an area of active research in recent years. The MERINO-2 study group was not able to find a difference between piperacillin-tazobactam and meropenem among patients with bloodstream infections with AmpC producing organisms, unfortunately, there were only five Serratia infections in that study (Stewart et al, 2021). Similarly, a recent meta-analysis of bloodstream infections with AmpC-producing organism also failed to show a difference between piperacillin-tazobactam and carbapenems among studies with modest cases of S. marcescens infections (Cheng et al, 2017).…”

Morganella morganii, an Emerging Cause of Bloodstream Infections

“… Morganella morganii has chromosomally encoded bla AmpC , which confers resistance to cephalosporins and penicillins ( 2 ). As a result, treatment with quinolones, aminoglycosides, co-trimoxazole, or carbapenems is usually recommended ( 3 – 6 ). However, the potential for Morganella morganii to acquire other resistance determinants has been increasingly recognized ( 7 ).…”

Microbiological and Clinical Characteristics of Bloodstream Infections in General Intensive Care Unit: A Retrospective Study

“…or K. pneumoniae BSI and ceftriaxone resistance, compared with meropenem treatment, definitive treatment with piperacillin-tazobactam did not result in non-inferior 30-day mortality ( 26 ). Stewart AG et al reported that piperacillin-tazobactam might lead to more microbiological failures among patients with bloodstream infection due to AmpC producers ( 27 ). Piperacillin tazobactam is not suitable for empirical treatment of ESBL positive bloodstream infection.…”