학술논문
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 Multicenter Randomized Controlled Trial (MERINO-2)
MAJOR ARTICLE
MAJOR ARTICLE
Document Type
Report
Author
Stewart, Adam G.; Paterson, David L.; Young, Barnaby; Lye, David C.; Davis, Joshua S.; Schneider, Kellie; Yilmaz, Mesut; Dinleyici, Rumeysa; Runnegar, Naomi; Henderson, Andrew; Archuleta, Sophia; Kalimuddin, Shirin; Forde, Brian M.; Chatfield, Mark D.; Bauer, Michelle J.; Lipman, Jeffrey; Harris-Brown, Tiffany; Harris, Patrick N.A.
Source
Open Forum Infectious Diseases. August 2021, Vol. 8 Issue 8
Subject
Language
English
ISSN
2328-8957
Abstract
AmpC [beta]-lactamase genes are chromosomal genes found in certain bacterial species (eg, Enterobacter spp, Klebsiella [formerly Enterobacter] aerogenes, Serratia marcescens, Citrobacter freundii, Providencia stuartii, Morganella morganii) [1, 2]. AmpC expression [...]
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 P-lactamase genes identified were [bla.sub.CMY-2], [bla.sub.DHA-17], [bla.sub.CMH-3], and [bla.sub.ACT-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. Keywords. ampC [beta]-lactamase; carbapenem; clinical trial; Enterobacterales; piperacillin-tazobactam.
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 P-lactamase genes identified were [bla.sub.CMY-2], [bla.sub.DHA-17], [bla.sub.CMH-3], and [bla.sub.ACT-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. Keywords. ampC [beta]-lactamase; carbapenem; clinical trial; Enterobacterales; piperacillin-tazobactam.