Effect of cefepime dose on mortality of patients with Gram-negative bacterial bloodstream infections: a prospective cohort study

Abstract

There are controversies regarding the association of cefepime therapy with increased mortality among patients with infections caused by Gram-negative bacteria (GNB). We evaluated the effect of cefepime on the mortality of patients with GNB bloodstream infections (BSIs). A prospective cohort study was conducted in adult patients with creatinine ≤1.5 mg/dL who received empirical therapy with cefepime for at least 48 h for BSIs caused by GNB. The outcome was hospital mortality. Potential clinical predictors, including a high-dose regimen (2 g every 8 h), were assessed. One hundred and thirteen patients were included. Most (78.8%) isolates had low cefepime MICs (≤0.25 mg/L). The overall hospital mortality was 35.4% [25.6% (10/39) and 40.5% (30/74) in patients receiving high-dose and usual-dose cefepime, respectively (P = 0.17)]. In a Cox regression model adjusted for cefepime MIC and propensity score, a high-dose regimen was independently associated with lower mortality rates [adjusted hazard ratio (aHR) 0.41; 95% CI 0.18-0.91; P = 0.029] while presentation with severe sepsis or septic shock was independently associated with higher mortality rates (aHR 4.10; 95% CI 1.78-9.40; P = 0.001). A trend to lower mortality rates was also found in the subgroup analysis of patients who had not switched antibiotic during therapy after adjustment for the latter variables. High-dose cefepime therapy was associated with lower mortality rates in patients with GNB BSIs, even for GNB with low cefepime MICs.