Lower Mortality with Meropenem vs. Piperacillin-Tazobactam in ESBL Bacteremia

Resistance to third- and fourth-generation cephalosporins by extended-spectrum beta-lactamase (ESBL) bacteria poses considerable challenges to the durability of our available antibiotics. Specifically, treatment of these increasingly common infections with carbapenems raises great concern for selecting carbapenem-resistant gram-negative resistance. Thus, carbapenem-sparing beta-lactam/beta-lactamase inhibitor (BL/BLI) therapy such as piperacillin-tazobactam (PT) may be considered for such infections because ESBL-harboring Enterobacteriaceae are generally susceptible in vitro. However, recent data suggest that PT may be inferior to meropenem in these settings.

To test the noninferiority of PT to meropenem in such infections, researchers performed a 26-center, 9-country randomized clinical trial comparing PT 4.5 g given intravenously every 6 hours (n=187) with meropenem 1 g IV every 8 hours (n=191) for 4 to 14 days, for treatment of bacteremia caused by ceftriaxone-resistant Escherichia coli and Klebsiella pneumoniae. The primary outcome measure was all-cause 30-day postrandomization mortality.

At 30 days, 23 (12.3%) of PT-treated patients and 7 (3.7%) of meropenem-treated patients died, a significant difference. Mortality was more pronounced with K. pneumoniae bacteremia (23% for PT, 0% for meropenem), non-UTI source (18.8% for PT, 4.8% for meropenem) and immunocompromised status (19.6% for PT, 2.5% for meropenem). Differences were smaller for urinary source of bacteremia (6.9% for PT, 3.1% for meropenem).