Are Current Levofloxacin Dosing Levels Sufficient for Critically Ill Patients?

HPLC was utilized to determine both total and unbound levofloxacin plasma concentrations
HPLC was utilized to determine both total and unbound levofloxacin plasma concentrations

This article is written live from ID Week 2017 Annual Meeting in San Diego, CA. MPR will be reporting news on the latest findings from leading experts in infectious diseases. Check back for more news from IDWeek 2017.


SAN DIEGO— According to results of a prospective, observational study presented at IDWeek 2017, “Levofloxacin 750mg IV q24h failed to achieve the optimal AUC:MIC ratio of ≥125 for susceptible Enterobacteriaceae in critically ill trauma patients.”

A total of 7 male, critically ill trauma patients with preserved renal function were included in the study and received 750mg of levofloxacin administered intravenously every 24 hours. Venous or arterial blood was sampled at various time points: at steady-state before dose administration, at 0.5, 4, 7, 12, and 24 hours after drug infusion. High-performance liquid chromatography (HPLC) was utilized to determine both total and unbound levofloxacin plasma concentrations. Additionally, several PK parameters as well as the cumulative fraction of response were assessed.

To calculate the ARCTIC score, 2 points were assigned if the patient's SCr was <0.7mg/dL or if the patient was male, 4 points were assigned if the patient was <56 years old, and 3 points were assigned if the patient was 56 to 75 years old.

The study authors reported an ARCTIC score of 6.3±1.6 points, indicating that renal clearance augmentation was probable. The patients included in the study had an average age of 56 years, an average weight of 108.4kg, and a mean eGFR of 150.9mL/min/1.73m2. Mean values for AUC, Vd, and CL were reported as 77.9±44.6µg•h/mL, 145.2±79.6L (1.9±1.1L/kg) and 12.8±7.3L/h (1.9±0.8mL/min/kg), respectively. The maximum MIC for which AUC:MIC ≥125 was reported as 0.62±0.36µg/mL.

Lead study author Kaitlin Pruskowski, PharmD, of the US Army Institute of Surgical Research, JBSA Ft Sam, in Houston, TX, stated, "Levofloxacin 750mg IV q24h failed to achieve the optimal AUC:MIC ratio of ≥125 for susceptible Enterobacteriaceae in critically ill trauma patients." 

According to this observational study, 750mg of levofloxacin administered intravenously every 24 hours did not achieve the total plasma AUC:MIC ratio of ≥125 that is recommended for gram-negative infections in critically ill trauma patients. Dr. Pruskowski added, “Increased drug exposure may be indicated for critically ill trauma patients to improve outcomes through PK-PD optimization.”

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Reference:

Pruskowski KA, Akers SK. Standard Levofloxacin Dosing May Be Insufficient in Critically Ill Trauma Patients. Poster presented at IDWeek; October 4–8, 2017; San Diego, CA. IDweek.org