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

J Antimicrob Chemother. 2014 Jun;69(6):1681-7. doi: 10.1093/jac/dku001. Epub 2014 Jan 27.


Objectives: 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).

Methods: 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.

Results: 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.

Conclusions: High-dose cefepime therapy was associated with lower mortality rates in patients with GNB BSIs, even for GNB with low cefepime MICs.

Keywords: Enterobacteriaceae; antimicrobial therapy; bacteraemia; pharmacokinetic/pharmacodynamic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-Bacterial Agents / administration & dosage*
  • Bacteremia / drug therapy*
  • Bacteremia / microbiology
  • Bacteremia / mortality*
  • Cefepime
  • Cephalosporins / administration & dosage*
  • Drug Resistance, Bacterial
  • Drug Substitution
  • Female
  • Gram-Negative Bacteria / drug effects
  • Gram-Negative Bacteria / isolation & purification
  • Gram-Negative Bacterial Infections / drug therapy*
  • Gram-Negative Bacterial Infections / microbiology
  • Gram-Negative Bacterial Infections / mortality*
  • Hospital Mortality
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Prospective Studies
  • Risk Factors
  • Treatment Outcome


  • Anti-Bacterial Agents
  • Cephalosporins
  • Cefepime