Background: ESBL-producing gram-negative bacilli are becoming increasingly common. Carbapenems are considered the treatment of choice for these infections, but they may in turn select for carbapenem-resistant gram-negative bacilli.
Study design: Open-label, noninferiority, randomized clinical trial.
Setting: Adult inpatients from nine countries (not including the United States).
Synopsis: Patients with at least one positive blood culture for ESBL E. coli or K. pneumoniae were screened. Of the initial 1,646 patients assessed, only 391 were enrolled (866 met exclusion criteria, 218 patients declined, and 123 treating physicians declined). Patients were randomized within 72 hours of the positive blood culture collection to either piperacillin/tazobactam 4.5 g every 6 hours or meropenem 1 g every 8 hours. Patients were treated from 4 to 14 days, with the total duration of antibiotics left up to the treating physician.
The primary outcome was all-cause mortality at 30 days after randomization. The study was stopped early because of a significant mortality difference between the two groups (12.3% in the piperacillin/tazobactam group versus 3.7% in the meropenem group).
The overall mortality rate was lower than expected. The sickest patients may have been excluded because the treating physician needed to approve enrollment. Because of the necessity for empiric antibiotic therapy, there was substantial crossover in antibiotics between the groups, although this would have biased the study toward noninferiority.
Bottom line: For patients with ESBL E. coli or K. pneumoniae blood stream infections, treatment with piperacillin/tazobactam was inferior to meropenem for 30-day mortality.
Citation: Harris PNA et al. 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. JAMA. 2018;320(10):984-94.
Dr. Gabriel is assistant professor of medicine and director of Preoperative Medicine and Medicine Consult Service in the division of hospital medicine at Mount Sinai Hospital, New York.