Clinical Outcomes in Patients With Gram-Negative Infections Treated With Optimized Dosing Cefepime Over Various Minimum Inhibitory Concentrations. (February 2018)

• Record Type: Journal Article
• Authors: Altshuler, Jerry; Guervil, David J.; Ericsson, Charles D.; Wanger, Audrey; Aitken, Samuel L.; Ostrosky-Zeichner, Luis
• Is Part Of: Journal of pharmacy practice. Volume 31:Number 1(2018:Feb.)
• Page Start: 34
• Page End: 39
• Publication Date: 2018-02
• Subjects: cefepime -- pharmacodynamics -- minimum inhibitory concentration -- gram-negative; Pharmacy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1177/0897190017696950
• Languages: English
• ISSNs: 0897-1900

Abstract

Background: The Clinical and Laboratory Standards Institute (CLSI) revised cefepime interpretive criteria, introducing the susceptible dose-dependent category for Enterobacteriaceae with a minimum inhibitory concentration (MIC) of 4 to 8 μg/mL in 2014. Limited clinical data support these new categories. This study compares outcomes of patients treated with standard and high-dose cefepime across various MICs. Methods: We retrospectively reviewed cases of pneumonia or bacteremia caused by gram-negative organisms treated with adequate doses of cefepime for ≥48 hours. Outcomes were compared for MICs of ≤2 (low), 4 (medium), and 8 μg/mL (high). The primary end point was clinical failure, the secondary end point was microbiological failure. Results: Ninety cases met the inclusion criteria: 46, 25, and 19 patients with low, medium, or high MIC, respectively. Multivariate logistic regression revealed that the medium (odds ratio [OR]: 9.13, P < .01) and high (OR: 6.79, P = .01) MIC groups had increased clinical failure. Conclusion: Cefepime therapy, even at CLSI-recommended doses, had an increased risk of clinical failure for gram-negative pathogens with MICs of 4 or 8 μg/mL. This finding suggests that higher dosing regimens (2 g every 8 hours or 1 g every 6 hours) may be necessary to treat serious gram-negative infections with elevated MICs.