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Clinical Outcomes in Patients With Gram-Negative Infections Treated With Optimized Dosing Cefepime Over Various

Jerry Altshuler1, David J Guervil2, Charles D Ericsson3

  • 11 Pharmacy Department, Mount Sinai Beth Israel, New York, NY, USA.

Journal of Pharmacy Practice
|December 28, 2017
PubMed
Abstract

Insights

Cefepime treatment failure increased for gram-negative infections with minimum inhibitory concentrations (MICs) of 4-8 μg/mL. Higher cefepime doses may be needed for these elevated MICs, challenging current guidelines.

Area of Science:

  • Infectious Diseases
  • Pharmacology
  • Clinical Microbiology

Background:

  • Clinical and Laboratory Standards Institute (CLSI) updated cefepime susceptibility criteria in 2014.
  • New criteria include a susceptible dose-dependent category for Enterobacteriaceae with minimum inhibitory concentrations (MICs) of 4-8 μg/mL.
  • Limited clinical data exist to support these revised cefepime interpretive criteria.

Purpose of the Study:

  • To compare clinical outcomes in patients treated with standard versus high-dose cefepime.
  • To evaluate cefepime efficacy across different MICs for gram-negative organisms.
  • To assess the impact of revised CLSI cefepime breakpoints on treatment outcomes.

Main Methods:

  • Retrospective review of 90 patients with pneumonia or bacteremia caused by gram-negative organisms.
  • Patients received adequate cefepime doses for ≥48 hours.
  • Outcomes analyzed based on cefepime MICs: ≤2 μg/mL (low), 4 μg/mL (medium), and 8 μg/mL (high).

Main Results:

  • Multivariate analysis showed increased clinical failure in patients with medium (OR: 9.13) and high (OR: 6.79) MICs.
  • 46 patients had low MICs, 25 had medium MICs, and 19 had high MICs.
  • Both medium and high MIC groups demonstrated statistically significant higher rates of clinical failure.

Conclusions:

  • Cefepime therapy, even at standard doses, is associated with higher clinical failure risk for gram-negative pathogens with MICs of 4 or 8 μg/mL.
  • Current CLSI-recommended doses may be insufficient for infections with elevated cefepime MICs.
  • Higher cefepime dosing regimens (e.g., 2g q8h or 1g q6h) might be required for serious gram-negative infections with higher MICs.
Keywords:
cefepimegram-negativeminimum inhibitory concentrationpharmacodynamics

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