A Retrospective Study Evaluating the Safety and Clinical Impact of High Dose (6.75 grams) Piperacillin-Tazobactam Dosing in Critically Ill Obese Patients for Pneumonia

<b>Background:</b> Piperacillin-tazobactam (PTZ) demonstrates time-dependent bactericidal activity, potentially increasing the need for higher dosing in obese and critically ill patients. However, limited information is available on the safety of higher dosing strategies. <b>Objective:</b> To evaluate the safety and clinical impact of high dose 6.75 g IV PTZ for the treatment of pneumonia in critically ill, obese (≥120 kg) patients vs standard dose 4.5 g IV PTZ. <b>Methods:</b> Retrospective, cohort study, multicenter in health-system consisting of four acute-care teaching hospitals. Adult patients weighing at least 120 kg on PTZ for pneumonia in the intensive care unit (ICU) from January 2013 to September 2018 were included. The primary outcome of the study was acute nephrotoxicity defined as initiation of renal replacement therapy and/or serum creatinine increase within 48 hours of last PTZ dose. Secondary outcomes included thrombocytopenia, 14-day all-cause mortality, and ICU length of stay (LOS). <b>Results:</b> One hundred thirty-six patients were included with 52 and 84 in 4.5 g PTZ and 6.75 g PTZ respectively. The rate of acute nephrotoxicity was comparable between cohorts (50% 4.5 g vs 40.5% 6.75 g, <i>P</i> = 0.277). High dose PTZ was not independently associated with acute nephrotoxicity after control for selected confounders. All secondary outcomes were similar. Concomitant vancomycin and calculated supratherapeutic vancomycin area under curve were not independently associated with increased nephrotoxicity. <b>Conclusions:</b> High dose PTZ was not associated with increased acute nephrotoxicity, thrombocytopenia, 14-day all-cause mortality, or ICU LOS. Additionally, more robust trials are needed to fully assess the clinical impact of 6.75 g PTZ dosing for critically ill, obese patients, for pneumonia.