1425. Population Pharmacokinetic Analysis of Ciprofloxacin and Levofloxacin in Critically Ill Trauma, Surgical, and Burn Patients

Abstract

BackgroundAntibiotic pharmacokinetics (PK) differ between critically ill and noncritically ill patients, as do the bacteria causing infection, yet dosing regimens are derived from noncritically ill populations. The purpose of this study was to examine the adequacy of ciprofloxacin and levofloxacin dosing in critically ill trauma, surgery, and burn patients for treating common nosocomial pathogens.MethodsTime–concentration curves derived from plasma samples in critically ill patients receiving ciprofloxacin 400 mg IV q12h (N = 11) or q8h (N = 5) or levofloxacin 750 mg IV q24h (N = 9) were used to calculate individual PK parameters and create population PK models. Monte-Carlo simulations were performed to assess the cumulative fraction of response (CFR) to achieve the target pharmacodynamic index (PDI) of AUC:MIC ≥ 125, using Gram-negative MIC distributions from the European Committee on Antimicrobial Susceptibility Testing.ResultsThe fit of both the ciprofloxacin and levofloxacin population models was improved with the addition of CrCl as a covariate. Despite simulating higher dosing regimens, such as ciprofloxacin 600 mg q8h and 800 mg q8h and levofloxacin 1,125 mg q24h and 1,500 mg q24h, only a single dosing regimen/Gram-negative species combination demonstrated a CFR ≥90%. This result was consistent with the finding that the maximum MICs at which individual patients achieved the target PDI were well below the CLSI breakpoints of ciprofloxacin and levofloxacin for Enterobacteriaceae, Pseudomonas, and Acinetobacter of ≤1 and ≤2 mg/mL, respectively.ConclusionIn critically ill trauma, surgical, and burn patients, standard dosing regimens of ciprofloxacin and levofloxacin failed to achieve PDIs sufficient to treat optimally Enterobacteriaceae, Pseudomonas, and Acinetobacter isolates with MICs up to the CLSI breakpoints. When increased doses were simulated, the CFR of all but one dose/species combination remained suboptimal. Individualized dosing guided by therapeutic drug monitoring may be an appropriate next step to improve fluoroquinolone efficacy in these critically ill patients.Disclosures All authors: No reported disclosures.