Clinical Evaluation of an Alternate Cefepime Dosing Protocol for Gram-Negative Bloodstream and Respiratory Infections

Abstract

Background. Optimization of antibiotic dosing regimens is critical to maintain efficacy. In 2011, our 650-bed academic medical center implemented an alternate dosing protocol for cefepime, which utilized automatic dose substitution to replace doses of 2 g every 12 hours with 1 g every 6 hours. Doses of 2 g every 8 hours are restricted to documented neutropenic fever only. Pharmacokinetic studies have demonstrated the ability of this alternate dosing strategy to achieve target attainment for Pseudomonas isolates up to an MIC of 8 mg/L but there is a lack of supporting clinical data. Methods. A retrospective cohort study was conducted between 1/08 and 12/14, comparing outcomes for traditional (TD) versus alternate dosing (AD) strategies. Inpatients ≥ 19 years old were included if they received ≥ 72 hours of cefepime for a documented Gram-negative bacteremia or pneumonia. Exclusion criteria were neutropenic fever, cystic fibrosis, or length of stay >100 days. The primary outcome was clinical cure, defined as resolution or improvement in leukocytosis and fever plus negative repeat blood cultures for bacteremia and improved oxygenation for pneumonia, within 7 days of starting cefepime. Secondary outcomes included hospital and ICU length of stay, in-hospital mortality, and 30-day readmission. Results. A total of 100 patients were included: 54 TD and 46 AD. Baseline characteristics were similar with overall mean age 60 years, 61% male, and mean Charlson comorbidity index of 3. Overall, 56% of patients had bacteremia, 35% had pneumonia, and 8% had both.More patients in the TD group received an additional active antibiotic (43% versus 7%, p = 0.0041), driven by use of fluoroquinolones. The most common pathogens isolated from cultures were Pseudomonas spp. (40%), Enterobacter spp. (19%), and Klebsiella spp. (19%). For Pseudomonas isolates with a specificMIC of 4 or 8 mg/L, 60% of TD regimens were considered inadequate to achieve target attainment compared to 0% of AD regimens (p < 0.0001). Clinical cure was similar for TD and AD groups (69% versus 73%, p = 0.821) and no signicant differences were noted for secondary outcomes. Conclusion. An alternate cefepime dosing protocol resulted in similar clinical outcomes for documented Gram-negative bloodstreamand respiratory infections compared to traditional dosing and decreased inappropriate dosing for Pseudomonas infections.