Evaluation of clinical outcomes in patients with Gram-negative bloodstream infections according to cefepime MIC

Abstract

Predicted and observed failures at higher cefepime MICs have prompted the Clinical and Laboratories Standards Institute (CLSI) to lower the susceptible breakpoint for Enterobacteriaceae to ≤2mg/L, with dose-dependent susceptibility at 4–8mg/L, while the susceptibility breakpoint for nonfermentative organisms remain unchanged at ≥8mg/L. The contribution of increasing cefepime MIC to mortality risk in the setting of aggressive cefepime dosing is not well defined. Patients who were treated with cefepime for Gram-negative blood stream infections (GNBSIs), including both Enterobacteriaceae and nonfermentative organisms, were screened for inclusion in this retrospective cohort study. Demographic and microbiologic variables were collected, including pathogen, cefepime MIC, dosage, and interval. The objective was to define a risk-adjusted mortality breakpoint for cefepime MICs. Secondarily, we looked at time to death and length of stay (LOS) postculture. Ninety-one patients were included in the analysis. Overall, 19 patients died and 72 survived. Classification and Regression Tree analysis identified an inhospital mortality breakpoint at a cefepime MIC between 2 and 4mg/L for patients with a modified Acute Physiology and Chronic Health Evaluation II score ≤16.5 (4.2% versus 25%, respectively). Multivariate logistic regression revealed increased odds of mortality at a cefepime MIC of 4mg/L (adjusted odds ratio [aOR] 6.47; 95% confidence interval [CI] 1.25–33.4) and 64mg/L (aOR 6.54, 95% CI 1.03-41.4). Those with cefepime MICs ≥4mg/L experienced a greater median intensive care unit LOS for survivors (16 versus 2days; P=0.026). Increasing cefepime MIC appears to predict inhospital mortality among patients who received aggressive doses of cefepime for GNBSIs, supporting a clinical breakpoint MIC of 2mg/L.