Effect of Obesity on Clinical Failure of Patients Treated With β-Lactams

BACKGROUND: Altered pharmacokinetics in obese patients raise concerns over worse clinical outcomes. This study assessed whether obese patients receiving a β-lactam have worse clinical outcomes compared to nonobese patients and to identify if therapeutic drug monitoring may be beneficial. METHODS: This multicenter, retrospective cohort included hospitalized adults admitted from July 2015 to July 2017 treated with a β-lactam as definitive monotherapy against a gram-negative bacilli for ≥72 hours. Patients were excluded if there was lack of source control or if polymicrobial infections required >1 antibiotic for definitive therapy. Patients were classified based on body mass index (BMI): nonobese (BMI ≤29.9 kg/m(2)) and obese (BMI ≥30.0 kg/m(2)). The primary outcome was clinical treatment failure, and secondary outcomes were hospital length of stay, inpatient all-cause mortality, and 30-day all-cause readmission. RESULTS: There were 257 (43.6%) obese patients and 332 (56.4%) nonobese patients included. The most common infections were urinary (50.9%) and respiratory (31.4%). Definitive treatment was driven by third-generation cephalosporins (46.9%) and cefepime (44.7%). Treatment failure occurred in 131 (51%) obese patients and 109 (32.8%) nonobese patients (P < .001). Obesity and respiratory source were independently associated with increased likelihood of treatment failure. Obese patients were hospitalized longer than nonobese patients (P = .002), but no differences were found for all-cause mortality (P = .117) or infection-related readmission (0 = 0.112). CONCLUSIONS: Obese patients treated with β-lactams have higher rates of treatment failure and longer hospitalization periods than nonobese patients. Future studies are needed to assess the impact of therapeutic drug monitoring and specific dosing recommendations for targeted infection types.