803. Incorporating Augmented Renal Clearance in the Clinical Pharmacodynamic Outcome Evaluation of Cefepime-Recipients with Gram-Negative Bacteremia
Session: Poster Abstract Session: Antimicrobial Agents: PK/PD Studies
Friday, October 9, 2015
Room: Poster Hall
Background: Recent studies suggest augmented renal clearance (ARC) predicts suboptimal beta-lactam concentrations. However, ARC effects have not been included in clinical cefepime pharmacokinetic-pharmacodynamic (PK-PD) outcome studies, nor in cefepime breakpoint revisions.

Methods: We retrospectively studied patients with gram-negative bacteremias from 2008-2013 to compare outcomes in those who received PK-PD optimized versus suboptimal cefepime doses after accounting for ARC (estimated GFR>130 ml/min/1.73 m2). The primary outcome was 30-day mortality or microbiologic failure. Secondary outcomes included bacteremia, hospital, and ICU duration. A multivariable logistic regression model was used to identify independent risk factors for microbiologic failure. Cohort assignment was based on cefepime MIC from Vitek-2 and results from a prospective PK study at our institution. Cefepime plasma concentrations from ARC and non-ARC patients were optimally fit to a population PK model and a 10,000-patient Monte-Carlo analysis was performed to estimate PTA of achieving 60% fT>MIC in ARC and non-ARC patients. Chi-square and Mann-Whitney U tests were used.

Results: Among 42 patients, 31.0% had burn injury, APACHE II 16±7, eGFR 106±87, and 35.7% had ARC. Klebsiella spp. (n=13), Pseudomonas (n=8), and E. coli (n=7) were most common. Population PK clearance in 4 ARC patients (eGFR 202±122) was 14.4 L/h and 8.8 L/h in 5 non-ARC patients (eGFR 99±20). In ARC, maximum cefepime doses resulted in a 51.5% PTA for MICs of 8 mg/L. Using these data and MICs, 32 were assigned to the PK-PD optimized and 10 to the suboptimal cohort. There were no differences in the primary outcome (15.6% versus 20%, p=0.74), bacteremia duration (4±6 versus 3±3 days, p=0.66), hospital duration (27±27 versus 51±56 days, p=0.19), and ICU duration (17±25 versus 11±18 days, p=0.36). Urinary source (OR 0.23, 95% CI 0.12-0.42), ARC (OR 2.91, 95% CI 0.55-15.27), coinfection (OR 6.25, 95% CI 1.04-37.7), and APACHE II >16 (OR 9.00, 95% CI 0.97-83.06) were not independent risk factors for microbiologic failure.

Conclusion: After accounting for ARC, no differences in clinical outcomes were noted in patients receiving PK-PD-optimized versus suboptimal cefepime doses for gram-negative bacteremias.

Rebecca L. Arneson, PharmD, San Antonio Military Medical Center, Fort Sam Houston, TX, Kevin S. Akers, MD, FIDSA, Brooke Army Medical Center, Fort Sam Houston, TX and Jason M. Cota, PharmD, MSc, University of the Incarnate Word, San Antonio, TX


R. L. Arneson, None

K. S. Akers, None

J. M. Cota, None

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