Meropenem versus piperacillin-tazobactam for definitive treatment of bloodstream infections caused by AmpC beta-lactamase producing Enterobacter spp., Citrobacter freundii, Morganella morganii, Providencia spp., or Serratia marcescens: a pilot multi-center 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.