Piperacillin-tazobactam may be detrimental to certain patients with suspected sepsis

Treatment with piperacillin-tazobactam in patients with suspected sepsis and no clear indication for antianaerobic coverage may do more harm than good, being associated with increased mortality risk and prolonged organ dysfunction when compared with cefepime, according to a retrospective study.

The study involved 7,569 adult patients (median age 63 years, 55 percent male) treated empirically for suspected sepsis. Of these patients, 4,523 were treated with vancomycin plus piperacillin-tazobactam and 3,046 were treated with vancomycin plus cefepime.

The primary endpoint was 90-day mortality. Secondary outcomes included organ failure–free, ventilator-free, and vasopressor-free days. Researchers used a 15-month piperacillin-tazobactam shortage period as an instrumental variable to address potential confounding in antibiotic selection.

Only 3 percent of the patients in the piperacillin-tazobactam group received the combination during the shortage. Variables such as age, Charlson Comorbidity Index score, Sequential Organ Failure Assessment score, or time to antibiotic administration did not significantly differ between the piperacillin-tazobactam and cefepime groups.

Instrumental variable analysis showed that piperacillin-tazobactam was associated a 5-percent (95 percent confidence interval [CI], 1.9–8.1) increase in absolute mortality at 90 days compared with cefepime. Moreover, patients who received piperacillin-tazobactam had 2.1-fewer (95 percent CI, 1.4–2.7) organ failure–free days, 1.1-fewer (95 percent CI, 0.57–1.62) ventilator-free days, and 1.5-fewer (95 percent CI, 1.01–2.01) vasopressor-free days.

The present data indicate that widespread use of empirical antianaerobic antibiotics in sepsis may be harmful.