1562. Safety and Efficacy of High-Dose Cefazolin Therapy in Obesity

BACKGROUND: Obesity leads to altered pharmacokinetics through changes in volume of distribution and clearance, which can impact antimicrobial dosing. Although there is data to support higher cefazolin pre-operative dosing for surgical prophylaxis, data evaluating treatment doses of cefazolin in obese patients is lacking. This study was designed to assess the safety and efficacy of high-dose (HD) cefazolin compared with traditional-dose (TD) cefazolin in obesity. METHODS: This was a multicenter, retrospective, cohort study of patients admitted from September 1, 2013 to August 31, 2018. Obese adults, defined as a BMI > 30 kg/m(2), receiving cefazolin for at least 48 hours for bacteremia or skin and soft-tissue infection were eligible for inclusion. Patients with creatinine clearances <30 mL/minute or positive MRSA cultures were excluded. TD cefazolin was defined as 1–2 g IV every 8 hours and HD cefazolin was defined as 2 g every 4–6 hours. Patients were matched 1:1 based on indication, severity of illness, and BMI. Primary objective was to compare rates of treatment-emergent adverse events (TEAE). Secondary outcomes included comparison of treatment failure rates and 30-day readmission. RESULTS: A total of 332 patients (166 matched pairs) were included in this analysis. Baseline demographics were similar between groups with the exception of higher age in the TD group (61.8 TD vs 55.1 HD; P < 0.001) and more males in the HD group (39.2% TD vs. 65.6% HD; P < 0.001). Median Charlson comorbidity index was also higher in the TD group [4 (2–6) TD vs. 3 (1–4) HD; P < 0.001]. There were no differences in TEAE between groups (24.1% TD vs. 16.9% HD; P = 0.103). Treatment failure occurred more frequently in the TD group (24.7% TD vs. 15.1% HD; P = 0.028), driven primarily by rates of readmission secondary to recurrence or relapse of the index infection (18.7% vs. 11.5%; P = 0.07). CONCLUSION: There were no differences in TEAE in patients who received TD cefazolin vs. HD cefazolin therapy. Obese patients receiving TD therapy experienced higher treatment failure than those receiving HD therapy. Dose-optimization strategies with cefazolin in obese patients should be further explored. [Image: see text] DISCLOSURES: All authors: No reported disclosures.