Effect of Piperacillin-Tazobactam vs Meropenem on 30-Day Mortality for Patients With E coli or Klebsiella pneumoniae Bloodstream Infection and Ceftriaxone Resistance

作者：Patrick N. A. Harris, Paul Anantharajah Tambyah, David Chien Lye, Yin Mo, Tau H. Lee, Mesut Yılmaz, Thamer H. Alenazi, Yaseen M. Arabi, Marco Falcone, Matteo Bassetti, Elda Righi, Benjamin A. Rogers, Souha Sami Kanj, Hasan S. Bhally, Jonathan R. Iredell, Marc Mendelson, Tom Hilary Boyles, David F M Looke, Spiros Miyakis, Genevieve B. Walls, Mohammed Al Khamis, Ahmed Zikri, Amy Crowe, Paul Robert Ingram, Nick Daneman, Paul Griffin, Eugene Athan, Penelope Lorenc, Peter Baker, Leah Wendy Roberts, Scott A. Beatson, Anton Y. Peleg, Tiffany Harris‐Brown, David L. Paterson · 发表于：JAMA · 年份：2018 · DOI：10.1001/jama.2018.12163 · 被引用次数：790 · 研究领域：Antibiotic Resistance in Bacteria、Antibiotics Pharmacokinetics and Efficacy、Nosocomial Infections in ICU

Importance: Extended-spectrum β-lactamases mediate resistance to third-generation cephalosporins (eg, ceftriaxone) in Escherichia coli and Klebsiella pneumoniae. Significant infections caused by these strains are usually treated with carbapenems, potentially selecting for carbapenem resistance. Piperacillin-tazobactam may be an effective "carbapenem-sparing" option to treat extended-spectrum β-lactamase producers. Objectives: To determine whether definitive therapy with piperacillin-tazobactam is noninferior to meropenem (a carbapenem) in patients with bloodstream infection caused by ceftriaxone-nonsusceptible E coli or K pneumoniae. Design, Setting, and Participants: Noninferiority, parallel group, randomized clinical trial included hospitalized patients enrolled from 26 sites in 9 countries from February 2014 to July 2017. Adult patients were eligible if they had at least 1 positive blood culture with E coli or Klebsiella spp testing nonsusceptible to ceftriaxone but susceptible to piperacillin-tazobactam. Of 1646 patients screened, 391 were included in the study. Interventions: Patients were randomly assigned 1:1 to intravenous piperacillin-tazobactam, 4.5 g, every 6 hours (n = 188 participants) or meropenem, 1 g, every 8 hours (n = 191 participants) for a minimum of 4 days, up to a maximum of 14 days, with the total duration determined by the treating clinician. Main Outcomes and Measures: The primary outcome was all-cause mortality at 30 days after randomization. A nonin...