812. Standard Levofloxacin Dosing May Be Insufficient in Critically Ill Trauma Patients
Session: Poster Abstract Session: Use of PK/PD to optimize existing antibiotics and antifungals
Thursday, October 5, 2017
Room: Poster Hall CD
Posters
  • Levofloxacin PK in trauma poster v4 resized.png (428.0 kB)
  • Background: Pharmacokinetics can be significantly affected by altered organ function and physiology of critically ill trauma patients. FDA-approved dosing of antimicrobials, including levofloxacin, may not be sufficient to achieve pharmacokinetic (PK)-pharmacodynamic (PD) relationships associated with optimal clinical outcomes. For levofloxacin, a total plasma AUC:MIC ratio ≥125 is recommended for gram-negative infections. Our objective was to determine whether standard-dose levofloxacin satisfied this PK-PD target in critically ill trauma patients.

    Methods: This was an IRB-approved, prospective, observational study of critically ill trauma patients with preserved renal function who received levofloxacin 750mg IV q24h. Venous or arterial blood was sampled at pharmacologic steady-state prior to dose administration, at 0.5, 4, 8, and 12 hours after the end of drug infusion, and prior to the next dose. Total and unbound levofloxacin plasma concentrations were determined by HPLC. PK parameters were estimated by non-compartmental analysis (NCA) using WinNonLin (Certara, Inc.). A Monte Carlo simulation was attempted (Crystal Ball, Oracle) using EUCAST MICs for relevant pathogens to determine the cumulative fraction of response (CFR).

    Results: Seven trauma patients (all male; mean age 56 ± 18.9 years; eGFR 150.9 ± 63.6 mL/min/1.73m2) were analyzed. All received levofloxacin 750 mg IV q24h. Augmented renal clearance was probable, reflected by ARCTIC score of 6.3 ± 1.6 points. AUC, Vd and CL were 77.9 ± 44.6 µg•h/mL, 145.2 ± 79.6 L (1.9 ± 1.1 L/kg) and 12.8 ± 7.3 L/h (1.9 ± 0.8 mL/min/kg), respectively. The maximum MIC for which a ratio of AUC:MIC ≥125 could be achieved was 0.623 µg/mL. AUC:MIC ≥125 (for EnterobacteriaceaeMIC susceptible breakpoint ≤2 µg/mL) was not achieved in any patients. Monte Carlo simulation was precluded by highly variable AUC values which could not be fit to a probability distribution, reflecting unpredictable drug exposure from standard doses.

    Conclusion: Levofloxacin 750 mg IV q24h failed to achieve the optimal AUC:MIC ratio of ≥125 for susceptible Enterobacteriaceae in critically ill trauma patients. Increased drug exposure may be indicated for critically ill trauma patients to improve outcomes through PK-PD optimization.

    Kaitlin A. Pruskowski, PharmD, BCPS, BCCCP and Kevin S. Akers, MD, FIDSA, US Army Institute of Surgical Research, JBSA Ft Sam Houston, TX

    Disclosures:

    K. A. Pruskowski, None

    K. S. Akers, None

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