Weighing the Odds: Novel β-Lactam/β-Lactamase Inhibitor Use in Hospital-Acquired and Ventilator-Associated Pseudomonas aeruginosa Pneumonia for Patients Who Are Morbidly Obese

Abstract

Abstract Background Pseudomonas aeruginosa is a leading cause of hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP). Novel β-lactam/β-lactamase inhibitor (BL/BLI) combinations are often used for these infections; however, limited data exist to guide the dosing of BL/BLI in patients who are morbidly obese. Thus, we sought to evaluate the clinical and safety endpoints of patients who are morbidly obese (body mass index ≥35 kg/m2) and non–morbidly obese (<35 kg/m2) and receiving BL/BLI for P aeruginosa HABP/VABP. Methods This retrospective study was based on a cohort of patients hospitalized at 2 urban academic medical centers in Detroit, Michigan, from August 2014 through February 2021 with P aeruginosa HABP/VABP who were receiving BL/BLI (ceftazidime/avibactam, ceftolozane/tazobactam, or meropenem/vaborbactam) for ≥72 continuous hours. The primary endpoint was presumed treatment failure, defined as the presence of all-cause in-hospital mortality or the continuation of infectious symptoms. Analyses were adjusted for possible confounding with inverse probability of treatment weighting. Multivariable regression was used to identify predictors of treatment failure. Results In total, 285 patients with HABP (61.4%) and/or VABP (56.1%) were enrolled (morbidly obese, n = 95; non–morbidly obese, n = 190). The median Acute Physiology and Chronic Health Evaluation II score was 23 (IQR, 13–26), and 60% of patients were admitted to the intensive care unit at index culture collection. Patients who were morbidly obese demonstrated significantly greater odds of presumed treatment failure vs those who were non–morbidly obese (58.9% vs 37.9%, respectively; adjusted odds ratio, 1.675 [95% CI, 1.465–1.979]). In multivariable analysis, morbid obesity (1.06; 95% CI, 1.02–1.79), prolonged time to BL/BLI initiation (1.47; 95% CI, 1.28–2.66), renal dose–adjusted BL/BLI in the first 48 hours of therapy (1.12; 95% CI, 1.09–1.75), and continuous renal replacement therapy during BL/BLI therapy (1.35; 95% CI, 1.06–1.68) were independently associated with increased odds of presumed treatment failure. Conclusions Among hospitalized patients receiving BL/BLI for P aeruginosa HABP/VABP, those who were morbidly obese had significantly greater odds of presumed treatment failure when compared with those who were non–morbidly obese.