Jerry Altshuler1, David J Guervil2, Charles D Ericsson3, Audrey Wanger4, Samuel L Aitken5,6, Luis Ostrosky-Zeichner3. 1. 1 Pharmacy Department, Mount Sinai Beth Israel, New York, NY, USA. 2. 2 Department of Pharmacy, Memorial Hermann-Texas Medical Center, Houston, TX, USA. 3. 3 Division of Infectious Diseases, University of Texas Health Science Center at Houston, Houston, TX, USA. 4. 4 Department of Pathology, University of Texas Health Science Center at Houston, Houston, TX, USA. 5. 5 Division of Pharmacy, University of Texas MD Anderson Cancer Center, Houston, TX, USA. 6. 6 Department of Clinical Sciences and Administration, University of Houston College of Pharmacy, Houston, TX, USA.
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.
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.
Authors: Grace E Benanti; Anne Rain T Brown; Terri Lynn Shigle; Jeffrey J Tarrand; Micah M Bhatti; Patrick M McDaneld; Samuel A Shelburne; Samuel L Aitken Journal: Antimicrob Agents Chemother Date: 2019-01-29 Impact factor: 5.191
Authors: Kap Sum Foong; Abigail L Carlson; Satish Munigala; Carey-Ann D Burnham; David K Warren Journal: Open Forum Infect Dis Date: 2019-07-28 Impact factor: 3.835