title: Levofloxacin pharmacokinetics and pharmacodynamics in patients with severe burn injury.
abstract: Levofloxacin pharmacokinetics were studied in 11 patients with severe burn injuries. Patients (values are means +/- standard deviations; age, 41 +/- 17 years; weight, 81 +/- 12 kg; creatinine clearance, 114 +/- 40 ml/min) received intravenous levofloxacin at 750 mg (n = 10 patients) or 500 mg (n = one patient) once daily. Blood samples were collected on day 1 of levofloxacin therapy; eight patients were studied again on days 4 to 6. The pharmacodynamic probability of target attainment (PTA) was evaluated by Monte Carlo simulation. Mean systemic clearance, half-life, and area under the concentration-time curve over 24 h after levofloxacin at 750 mg were 9.0 +/- 3.2 liters/h, 7.8 +/- 1.6 h, and 93 +/- 31 mg . h/liter, respectively. There were no differences in pharmacokinetic parameters between day 1 and day 4; however, large intrapatient and interpatient variability was observed. Levofloxacin pharmacokinetics in burned patients were similar to those reported in other critically ill populations. Levofloxacin at 750 mg achieved >90% PTA for gram-negative and gram-positive pathogens with MICs of < or =0.5 microg/ml and MICs of < or =1 microg/ml, respectively. However, satisfactory PTA was not obtained with less-susceptible gram-negative organisms with MICs of 1 microg/ml or any organism with a MIC of > or =2 microg/ml. The results of this study indicate that levofloxacin should be administered at 750 mg/day for treatment of systemic infections in severely burned patients. However, even 750 mg/day may be inadequate for gram-negative organisms with MICs of 1 to 2 microg/ml even though they are defined as susceptible. Alternative antibiotics or treatment strategies should be considered for infections due to these pathogens.
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, University of Colorado Health Sciences Center, Denver, 80262, USA.
authors.forename: Tyree H
authors.initials: TH
authors.lastname: Kiser
authors.forename: Dorie W
authors.initials: DW
authors.lastname: Hoody
authors.forename: Marilee D
authors.initials: MD
authors.lastname: Obritsch
authors.forename: Colleen O
authors.initials: CO
authors.lastname: Wegzyn
authors.forename: Paulus C
authors.initials: PC
authors.lastname: Bauling
authors.forename: Douglas N
authors.initials: DN
authors.lastname: Fish
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019540:Area Under Curve; D002056:Burns / Q000150:complications* / Q000382:microbiology; D003198:Computer Simulation; D005260:Female; D006207:Half-Life; D006801:Humans; D064704:Levofloxacin; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009010:Monte Carlo Method; D015242:Ofloxacin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D064704:Levofloxacin; D015242:Ofloxacin