Harris PNA, et al. - Researchers investigated the efficacy of definitive therapy with piperacillin-tazobactam vs meropenem (a carbapenem) in patients with bloodstream infection caused by ceftriaxone-nonsusceptible Escherichia coli or Klebsiella pneumoniae to assess whether piperacillin-tazobactam can be used as carbapenem-sparing therapy in these patients. Outcomes suggested non-inferiority of definitive treatment with piperacillin-tazobactam to meropenem regarding 30-day mortality. Thus, the findings do not support use of piperacillin-tazobactam vs meropenem in this setting.

Methods

• Hospitalized patients enrolled from February 2014 to July 2017 were included in this noninferiority, parallel group, multicenter (sites, 26; countries, 9), randomized clinical trial.
• Adult patients having ≥ 1 positive blood culture with E. coli or Klebsiella spp testing nonsusceptible to ceftriaxone but susceptible to piperacillin-tazobactam were eligible for inclusion.
• Researchers screened 1,646 patients; of these, they included 391 in the study.
• Patients were randomized 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; the total duration was determined by the treating clinician.
• All-cause mortality at 30 days after randomization was assessed as the primary outcome.
• They used a noninferiority margin of 5%.

Results

• The primary outcome was assessed in 378 (99.7%) patients who completed the trial among 379 patients (mean age, 66.5 years; 47.8% were women); they were randomized to receive ≥1 dose of study drug and were included in the primary analysis population.
• The primary outcome of mortality at 30 days was met by 23 of 187 patients (12.3%) randomized to piperacillin-tazobactam vs 7 of 191 (3.7%) who were randomized to meropenem (risk difference, 8.6% [1-sided 97.5% confidence interval: −∞ to 14.5%]; P=0.90 for noninferiority).
• In an analysis of the per-protocol population, consistent effects were evident.
• Nonfatal serious adverse events were recorded in 5 of 188 patients (2.7%) in the piperacillin-tazobactam group and 3 of 191 (1.6%) in the meropenem group.