Pharmacokinetics and pharmacodynamics of levofloxacin in critically ill patients with ventilator-associated pneumonia.

The pharmacokinetics of levofloxacin and outcome of levofloxacin therapy in critically ill patients with ventilator-associated pneumonia (VAP) were assessed. Further theoretical considerations regarding the pharmacokinetic/pharmacodynamic (PK/PD) appropriateness of levofloxacin therapy were made. Twelve patients completed the study, all of whom were treated with a standard intravenous levofloxacin regimen (2x500 mg on Day 1, then 1x500 mg daily). The maximum free plasma levofloxacin concentration (fC(max,ss)) and the area under the free concentration-time curve (fAUC) were 8.13+/-1.64 mg/L and 49.63+/-15.60 mgh/L, respectively. Optimal PK/PD target parameters were achieved in 10 patients; clinical success was attained in 11 of the 12 patients who completed the study. Bacterial eradication was obtained in 9 of the 11 cases with microbiologically confirmed bacteriological aetiology. Intravenous levofloxacin therapy (500 mg/day) was proven to be an effective regimen in this limited number of patients with VAP. However, theoretical considerations based on PK/PD indices predict that, with the current susceptibility breakpoint of 2mg/L, even higher levofloxacin doses (e.g. 1000 mg) could result in treatment failures in infections caused by pathogens labelled as levofloxacin-susceptible in the microbiology report.