Reviewed by: Jose Lucar, MD, The George Washington University
Acutely ill patients with obesity present challenges for medical management of infections, including proper medication dosing, and available evidence suggests an association between obesity and poor outcomes. A recent study adds evidence to support that association1.
Patients with obesity are at risk for changes in drug pharmacokinetics (PK) that can result in altered drug exposure and therapeutic failure compared to those without obesity2. A recent guidance document focused on antibiotic dosing in adults with obesity recommended no change in dosing for novel β-lactam/β-lactamase inhibitor (BL/BLI) combinations that are often used to treat challenging Pseudomonas aeruginosa infections3.
In this retrospective cohort study, Kunz Coyne and collaborators evaluated the effect of morbid obesity in patients who received ceftazidime-avibactam (CZA), ceftolozane-tazobactam (C/T), or meropenem-vaborbactam (MVB) as definitive therapy for P. aeruginosa hospital-acquired and ventilator-associated pneumonia (HAP/VAP) at 2 academic medical centers in Detroit, Michigan between August 2014 and February 2021. The authors defined morbid obesity as having a BMI ≥35 kg/m2. For inclusion, patients had P. aeruginosa in a respiratory culture, met the definition of lower respiratory tract infection per Centers for Disease Control and Prevention’s National Healthcare Safety Network, received in vitro active antimicrobial therapy within 72 hours of a positive respiratory culture, and received their first course of ≥72 continuous hours of a novel BL/BLI combination at recommended doses. The primary outcome of the study was a composite of presumed treatment failure, defined as all-cause hospital mortality or ongoing symptoms attributable to P. aeruginosa HAP/VAP. Propensity scores and inverse probability of treatment weighting (IPTW) were generated to ensure comparability between groups.
The authors assigned 285 patients into two groups: 95 with morbid obesity and 190 without morbid obesity, 60% of which were admitted to the ICU at the time of culture collection. The receipt of each BL/BLI combination was similar between groups. In the IPTW analysis, patients with morbid obesity had a higher likelihood of presumed treatment failure versus (adjusted OR, 1.675; 95% CI, 1.465–1.979). In the multivariable logistic regression model, independent factors associated with presumed treatment failure were morbid obesity, prolonged time to BL/BLI initiation, renal dose–adjusted BL/BLI combination in first 48 hours of therapy, and the need for continuous renal replacement therapy.
Limitations of this study include those associated with a retrospective design and potential confounding, lack of generalizability due to a single catchment area, limitations of propensity score analyses, the definition used for morbid obesity (BMI ≥35 mg/kg2) may not align with other studies, and lack of PK data. In conclusion, further study is needed to ensure appropriate dosing of antibiotics for patients with obesity to minimize potential negative outcomes of inadequate treatment.