Does Critical Illness Change Levofloxacin Pharmacokinetics?

Area of Science:

• Pharmacology
• Critical Care Medicine
• Clinical Pharmacy

Background:

• Levofloxacin is a frequently used antibiotic in critically ill patients.
• Existing data suggest that nonstandard dosing regimens may be necessary for this population.

Purpose of the Study:

• To compare the population pharmacokinetics of levofloxacin in critically ill versus non-critically ill patients.
• To determine if critical illness independently affects levofloxacin pharmacokinetic parameters.

Main Methods:

• Prospective pharmacokinetic study involving adult patients receiving intravenous levofloxacin.
• Blood samples were collected on days 1 or 2 of therapy for plasma analysis.
• Population pharmacokinetic analysis was performed using Pmetrics with a two-compartment linear model.

Main Results:

• Thirty-five patients (18 critically ill) were included in the analysis.
• Creatinine clearance was the only covariate significantly associated with levofloxacin clearance.
• Critical illness did not significantly impact any pharmacokinetic parameter, with altered renal function being the primary driver.

Conclusions:

• Critical illness does not appear to have an independent effect on levofloxacin pharmacokinetics beyond its impact on renal function.
• Levofloxacin dosing optimization in critically ill patients should prioritize assessment of renal function and consider pathogen-specific minimum inhibitory concentrations (MICs).