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

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.