title: Pharmacokinetics and pharmacodynamics of levofloxacin in critically ill patients with ventilator-associated pneumonia.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacy, Faculty of Pharmacy, University of Szeged, H-6725 Szeged, Szikra u. 8, Hungary. benko@clph.szote.u-szeged.hu
authors.forename: Ria
authors.initials: R
authors.lastname: Benko
authors.forename: Maria
authors.initials: M
authors.lastname: Matuz
authors.forename: Peter
authors.initials: P
authors.lastname: Doro
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Peto
authors.forename: Anna
authors.initials: A
authors.lastname: Molnar
authors.forename: Edit
authors.initials: E
authors.lastname: Hajdu
authors.forename: Erzsebet
authors.initials: E
authors.lastname: Nagy
authors.forename: Janos
authors.initials: J
authors.lastname: Gardi
authors.forename: Gyongyver
authors.initials: G
authors.lastname: Soos
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001424:Bacterial Infections / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology; D016638:Critical Illness; D005260:Female; D006801:Humans; D064704:Levofloxacin; D008297:Male; D008875:Middle Aged; D015242:Ofloxacin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy* / Q000382:microbiology; D011446:Prospective Studies
chemical_list: D000900:Anti-Bacterial Agents; D064704:Levofloxacin; D015242:Ofloxacin