Is it safe to use high-dose PTZ in critically ill patients with obesity?

High piperacillin-tazobactam (PTZ) dosing does not lead to increased acute nephrotoxicity, thrombocytopenia, 14-day all-cause mortality, or intensive care unit (ICU) length of stay (LOS), suggests a recent study.

This retrospective, cohort study was conducted across four acute-care teaching hospitals and included 136 adult patients weighing at least 120 kg on PTZ for pneumonia in the ICU from January 2013 to September 2018.

Acute nephrotoxicity, the primary outcome, was defined as initiation of renal replacement therapy or serum creatinine increase within 48 hr of last PTZ dose. Other outcomes included thrombocytopenia, 14-day all-cause mortality, and ICU LOS.

Of the eligible patients, 52 received the 4.5-g dose, and 84 received the 6.75-g dose. The rate of acute nephrotoxicity was similar between the treatment groups (50 percent vs 40.5 percent; p=0.277). After controlling for selected confounding factors, treatment with high-dose PTZ did not show an independent association with acute nephrotoxicity. All secondary outcomes were also comparable between groups.

Similarly, concomitant vancomycin and calculated supratherapeutic vancomycin area under the curve did not independently correlate with increased nephrotoxicity.

“Additionally, more robust trials are needed to fully assess the clinical impact of 6.75-g PTZ dosing for critically ill patients [with obesity] for pneumonia,” the authors said. 

“PTZ demonstrates time-dependent bactericidal activity, potentially increasing the need for higher dosing in critically ill patients [with obesity],” they noted.