1992. Pharmacokinetics of Ciprofloxacin in Critically Ill Burn and Non-burn Trauma Patients
Session: Poster Abstract Session: Antimicrobial Pharmacokinetics and Pharmacodynamics
Saturday, October 29, 2016
Room: Poster Hall
Posters
  • Poster Presentation IvinsOKeefe.pdf (3.7 MB)
  • Background: Pharmacokinetic (PK) and pharmacodynamic (PD) parameters altered by organ dysfunction and rising MICs, respectively, complicate antibiotic use in critically ill patients, especially burn patients. Therapeutic efficacy with conventional dosing regimens thus is less likely. With ciprofloxacin, Cmax:MIC is the PK/PD parameter associated with early bactericidal activity, whereas AUC24:MIC better correlates with clinical outcome. For ciprofloxacin, a total plasma AUC:MIC ≥125 is recommended to optimally treat gram-negative infections. The objective of this research is to evaluate the adequacy of ciprofloxacin dosing in critically ill burn and non-burn trauma patients.

    Methods: Plasma samples were collected at steady-state at timed intervals after a single 400mg IV dose from burn patients receiving ciprofloxacin q12h or q8h, and ICU trauma patients dosed q12h (N=3, 3, and 8). Drug levels were determined by HPLC. PK parameters were estimated by non-compartmental analysis using WinNonLin (Certara, Inc.). A 10,000 subject Monte Carlo simulation was performed using EUCAST MIC distributions to determine the cumulative fraction of response (CFR) for A. baumannii, P. aeruginosa, K. pneumoniae, E. cloacae, and E. coli (Crystal Ball, Oracle).

    Results: PK and demographic parameters did not differ significantly between the groups, nor did presumed augmented renal clearance (eGFR>120 ml/min/1.73m2) significantly affect weight-based clearance, volume of distribution or AUC24. The maximum MIC at which a ratio of AUC:MIC ≥125 could be achieved was 0.373 ±0.375 µg/mL, 0.539±0.429 µg/mL, and 0.344 ±0.113 µg/mL for burn patients dosed q12h, q8h, and non-burn trauma ICU patients dosed q12h, respectively. Using EUCAST MICs, Monte Carlo simulation revealed a CFR ranging from 56.7% in burn q12h patients with A. baumannii to 100% in all groups with E. cloacae.

    Conclusion: Neither q12h nor q8h ciprofloxacin dosing achieved the optimal AUC:MIC ratio of ≥125 in critically ill burn or non-burn patients up to the susceptible breakpoint of 1 µg/mL for Enterobacteriaceae. More frequent dosing or larger doses could achieve optimal PK-PD at higher MICs, potentially improving ciprofloxacin efficacy in critically ill burn and trauma patients.

    Kelly Ivins-O'keefe, A.B., Uniformed Services University of the Health Sciences, Bethesda, MD and Kevin S. Akers, MD, FIDSA, US Army Institute of Surgical Research, Fort Sam Houston, TX; Infectious Disease Service, San Antonio Military Medical Center, Fort Sam Houston, TX; Dept. of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD

    Disclosures:

    K. Ivins-O'keefe, None

    K. S. Akers, None

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