Cefepime vs Piperacillin-Tazobactam for Hospital-Acquired Infection

Patients who develop health care associated infections require extended spectrum antibiotic therapy, which usually consists of an antipseudomonal beta-lactam and vancomycin. Carbapenems have excellent activity against pseudomonas, but are usually not used first-line given the concerns for antimicrobial resistance. This leaves cefepime and piperacillin-tazobactam (pip-taz) as the drugs of choice for empiric therapy at most institutions.

Given that there is no data for clinical superiority for either agent, institutions usually let their local antimicrobial resistance patterns and their drug acquisition costs dictate choice of either cefepime or pip-taz. Recently, limited data has suggested that pip-taz may augment the renal toxicity of vancomycin, casting doubt on the suitability of this drug as a first-line antipseudomonal beta-lactam. In this week’s issue of TT, we discuss the ACORN study, which compared the outcomes of cefepime versus pip-tazo in patients with hospital acquired infections.

Point 3: Signals for differing safety profiles

The ACORN study randomized patients with hospital acquired infections in the emergency department or the intensive care unit to either cefepime or pip-tazo. The primary outcome was the highest stage of acute kidney injury or death by day 14, measured on a 5-level ordinal scale ranging from no acute kidney injury to death. A key secondary outcome was the number of days alive and free of delirium and coma within 14 days.

There were no differences between agents with respect to any of the renal endpoints in the trial. Interestingly, a total of 252 patients (20.8%) in the cefepime group experienced coma or delirium between enrollment and day 14 compared with 225 patients (17.3%) in the piperacillin-tazobactam group (absolute difference, 3.4% [95% CI, 0.3%-6.6%]). These results were consistent even when adjusting for confounding variables like receipt of sedation.

Point 2: Reassuring both drugs are acceptable first line agents

These data are important for dispelling the myth that pip-tazo causes more nephrotoxicity when combined with vanco as compared to cefepime. The increased risk of neurotoxicity is not surprising as this is a known side effect of cefepime. Ultimately, the choice of which agent to use will still likely come down to acquisition price and local resistance patterns.