Title |
Effect of Piperacillin-Tazobactam vs Meropenem on 30-Day Mortality for Patients With E coli or Klebsiella pneumoniae Bloodstream Infection and Ceftriaxone Resistance: A Randomized Clinical Trial.
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Published in |
JAMA: Journal of the American Medical Association, September 2018
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DOI | 10.1001/jama.2018.12163 |
Pubmed ID | |
Authors |
Patrick N A Harris, Paul A Tambyah, David C Lye, Yin Mo, Tau H Lee, Mesut Yilmaz, Thamer H Alenazi, Yaseen Arabi, Marco Falcone, Matteo Bassetti, Elda Righi, Benjamin A Rogers, Souha Kanj, Hasan Bhally, Jon Iredell, Marc Mendelson, Tom H Boyles, David Looke, Spiros Miyakis, Genevieve Walls, Mohammed Al Khamis, Ahmed Zikri, Amy Crowe, Paul Ingram, Nick Daneman, Paul Griffin, Eugene Athan, Penelope Lorenc, Peter Baker, Leah Roberts, Scott A Beatson, Anton Y Peleg, Tiffany Harris-Brown, David L Paterson |
Abstract |
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. 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. 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. 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. The primary outcome was all-cause mortality at 30 days after randomization. A noninferiority margin of 5% was used. Among 379 patients (mean age, 66.5 years; 47.8% women) who were randomized appropriately, received at least 1 dose of study drug, and were included in the primary analysis population, 378 (99.7%) completed the trial and were assessed for the primary outcome. A total of 23 of 187 patients (12.3%) randomized to piperacillin-tazobactam met the primary outcome of mortality at 30 days compared with 7 of 191 (3.7%) randomized to meropenem (risk difference, 8.6% [1-sided 97.5% CI, -∞ to 14.5%]; P = .90 for noninferiority). Effects were consistent in an analysis of the per-protocol population. Nonfatal serious adverse events occurred in 5 of 188 patients (2.7%) in the piperacillin-tazobactam group and 3 of 191 (1.6%) in the meropenem group. Among patients with E coli or K pneumoniae bloodstream infection and ceftriaxone resistance, definitive treatment with piperacillin-tazobactam compared with meropenem did not result in a noninferior 30-day mortality. These findings do not support use of piperacillin-tazobactam in this setting. anzctr.org.au Identifiers: ACTRN12613000532707 and ACTRN12615000403538 and ClinicalTrials.gov Identifier: NCT02176122. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 178 | 23% |
United Kingdom | 51 | 7% |
Spain | 47 | 6% |
Australia | 40 | 5% |
Saudi Arabia | 20 | 3% |
France | 16 | 2% |
Colombia | 15 | 2% |
Canada | 13 | 2% |
Mexico | 13 | 2% |
Other | 113 | 14% |
Unknown | 276 | 35% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 477 | 61% |
Practitioners (doctors, other healthcare professionals) | 155 | 20% |
Scientists | 139 | 18% |
Science communicators (journalists, bloggers, editors) | 10 | 1% |
Unknown | 1 | <1% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 807 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Other | 116 | 14% |
Researcher | 100 | 12% |
Student > Ph. D. Student | 63 | 8% |
Student > Bachelor | 63 | 8% |
Student > Postgraduate | 55 | 7% |
Other | 175 | 22% |
Unknown | 235 | 29% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 325 | 40% |
Pharmacology, Toxicology and Pharmaceutical Science | 58 | 7% |
Immunology and Microbiology | 41 | 5% |
Biochemistry, Genetics and Molecular Biology | 27 | 3% |
Nursing and Health Professions | 15 | 2% |
Other | 67 | 8% |
Unknown | 274 | 34% |