Clinical question: In patients with undifferentiated sepsis without an indication for anaerobic coverage, is there increased mortality with the combined use of vancomycin/piperacillin-tazobactam versus vancomycin/cefepime?
Background: Guideline-recommended treatment of sepsis entails a combination regimen of either vancomycin/piperacillin-tazobactam or vancomycin/cefepime. Studies have suggested that empiric treatment of sepsis with anti-anaerobic antibiotics, such as piperacillin-tazobactam, is associated with more adverse outcomes compared to anaerobe-sparing antibiotics, such as cefepime. A recent trial (ACORN) showed no difference in 14-day mortality between the two drugs. ACORN, however, was limited by analyzing only short-term outcomes.
Study design: Retrospective cohort study
Setting: University of Michigan Medical Center emergency department (ED)
Synopsis: The study involved 7,569 adult patients (median age, 63 years) who were admitted to the ED from 2014 through 2018 with undifferentiated suspected sepsis who had: blood samples drawn for cultures upon arrival to the ED; evidence of acute organ dysfunction in the first 24 hours after ED presentation; and treatment with antibiotics for at least one day upon ED arrival. Patients who were treated with vancomycin/piperacillin-tazobactam were compared with those who received vancomycin/cefepime. Patients with clear indications for anaerobic coverage were excluded. The primary outcome was 90-day mortality. Secondary outcomes included organ failure-free, ventilator-free, and vasopressor-free days. Piperacillin/tazobactam was associated with an absolute mortality increase of 5.0% at 90 days (95% CI, 1.9 to 8.1); 2.1 (95% CI, 1.4 to 2.7) fewer organ failure-free days; 1.1 (95% CI, 0.57 to 1.62) fewer ventilator-free days, and 1.5 (95% CI, 1.01 to 2.01) fewer vasopressor-free days. The nonrandomized design is the study’s primary limitation. Generalizability is a further limitation, as the study was conducted at a single academic medical center.
Bottom line: Among patients with undifferentiated sepsis without an indication for anaerobic coverage treated with vancomycin, the addition of piperacillin-tazobactam was associated with a higher 90-day mortality than cefepime, suggesting that empiric anaerobic coverage in sepsis may be harmful.
Citation: Chanderraj R, et al. Mortality of patients with sepsis administered piperacillin-tazobactam vs cefepime. JAMA Intern Med. 2024;184(7):769-77.
Dr. Kim
Dr. Kim is a hospitalist in the division of hospital medicine at the Mount Sinai Health System and an assistant professor of medicine at the Icahn School of Medicine at Mount Sinai in New York.