Relation between flomoxef minimum inhibitory concentrations and clinical outcomes of patients treated with flomoxef for Enterobacteriaceae bacteremia

BACKGROUND: Flomoxef is potentially effective against β-lactamase-producing Enterobacteriaceae because limited clinical data demonstrate its effectiveness against Enterobacteriaceae bloodstream infections (BSIs) based on its minimum inhibitory concentrations (MICs). This study was conducted to determine the optimal breakpoints based on the survival of patients with Enterobacteriaceae BSIs treated with flomoxef. METHODS: The 30-day crude mortality rate was analyzed among 224 adults who initiated flomoxef monotherapy for Enterobacteriaceae BSIs at a medical center over a 3-year period, according to the flomoxef MICs of the initial isolates. The outcome was evaluated by classification and regression tree modeling and by logistic regression analysis. RESULTS: The 30-day crude mortality was approximately two fold greater in patients whose isolates had flomoxef MICs of ≥2 mg/L (54.9% [62/113]) than in those with isolates with MICs of ≤1 mg/L (26.1% [29/111]); the differences were significant in bivariate analysis (P<0.01) and in survival analysis (log-rank test; P<0.001). The classification and regression tree analysis revealed a split between MICs of 1 and 2 mg/L and predicted the same difference in mortality, with a P-value of <0.001. Flomoxef for Enterobacteriaceae BSIs caused by isolates with flomoxef MICs of ≥2 mg/L was an independent predictor of 30-day crude mortality (adjusted OR 3.76, 95% CI 1.94–7.29). CONCLUSION: Patients with Enterobacteriaceae bacteremia who received flomoxef had a lower 30-day crude mortality when the flomoxef MICs of the isolates were ≤1 mg/L than those with MICs ≥2 mg/L.