Meropenem Versus Piperacillin-Tazobactam for Definitive Treatment of Bloodstream Infections Caused by AmpC β-Lactamase–Producing <i>Enterobacter</i> spp, <i>Citrobacter freundii</i>, <i>Morganella morganii</i>, <i>Providencia</i> spp, or <i>Serratia marcescens</i>: A Pilot Multicenter Randomized Controlled Trial (MERINO-2)
Adam G. Stewart, David L. Paterson, Barnaby Edward Young, David Chien Lye, Joshua S. Davis, Kellie E. Schneider, Mesut Yılmaz, Rumeysa Dinleyici, Naomi Runnegar, Andrew Henderson, Sophia Archuleta, Shirin Kalimuddin, Brian M. Forde, Mark D. Chatfield, Michelle J. Bauer, Jeffrey Lipman, Tiffany Harris‐Brown, Patrick N. A. Harris, Po Ying Chia, Gail Brenda Cross, Jyoti Somani, Gabriel Yan
Abstract
Abstract Background Carbapenems are recommended treatment for serious infections caused by 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. Eleven 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% confidence interval {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% vs 9% of microbiological relapses were seen in the piperacillin-tazobactam and meropenem arms, respectively. Susceptibility to piperacillin-tazobactam and meropenem using broth microdilution was found in 96.5% and 100% of isolates, respectively. The most common AmpC β-lactamase genes identified were blaCMY-2, blaDHA-17, blaCMH-3, and blaACT-17. No ESBL, OXA, or other carbapenemase genes were identified. Conclusions Among patients with bloodstream infection due to AmpC producers, piperacillin-tazobactam may lead to more microbiological failures, although fewer microbiological relapses were seen. Clinical Trials Registration NCT02437045.