Defining clinical exposures of cefepime for Gram negative bloodstream infections that are associated with improved survival.
Antimicrob Agents Chemother. 2015 Dec 14;
Authors: Rhodes NJ, Kuti JL, Nicolau DP, Van Wart S, Nicasio AM, Liu J, Lee BJ, Neely MN, Scheetz MH
The fT>MIC necessary to prevent mortality among cefepime-treated patients with Gram-negative bloodstream infections (GNBSI) is poorly defined. We conducted a retrospective study of adult patients with GNBSI. Eligible cases were frequency matched to ensure categorical representation from all MICs. Organism, MIC, infection source, gender, age, serum creatinine, weight, antibiotic history, and modified APACHE II were collected from hospital records. Two population pharmacokinetic models (Models 1 and 2) were used to impute exposures over the first 24-hours in each patient from mean model parameters, covariates, and dosing history. From the imputed exposures, survival thresholds for fT>MIC were identified using classification and regression tree (CART) analysis and analyzed as nominal variables for univariate and multivariate regressions. A total of 180 patients were included in the analysis, of whom 13.9% died and 86.1% survived. Many patients (46.7% [n=84/180]) received combination therapy with cefepime. Survivors had higher mean (SD) fT>MIC compared to those who died (Model 1: 74.2% [29.6] vs. 52.1% [33.8], P<0.001; Model 2: 85.9% [24.0] vs. 64.4% [31.4], P<0.001). CART identified fT>MIC threshold values for greater survival according to Models 1 and 2 at >68% and >74%, respectively. Survival was improved for those with fT>MIC > 68% (Model 1: aOR 7.12, 95% CI 1.90-26.7; P=0.004) and > 74% (Model 2: aOR 6.48; 95% CI 1.90-22.1), after controlling for clinical covariates. Similarly, each 1% increase in cefepime fT>MIC resulted in a 2% improvement in multivariate survival probability (P=0.015). Achieving a cefepime fT>MIC of 68-74% was associated with a higher odds of survival for patients with GNBSI. Regimens targeting this exposure should be aggressively pursued.
PMID: 26666929 [PubMed - as supplied by publisher]