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Antimicrobial Agents and Chemotherapy, June 2006, p. 1937-1945, Vol. 50, No. 6
0066-4804/06/$08.00+0     doi:10.1128/AAC.01466-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Levofloxacin Pharmacokinetics and Pharmacodynamics in Patients with Severe Burn Injury

Department of Clinical Pharmacy, School of Pharmacy, University of Colorado Health Sciences Center, Denver, Colorado,¹ Department of Pharmacy Services, University of Colorado Hospital, Denver, Colorado,² Department of Pharmacy: Clinical and Administration Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Tulsa, Oklahoma,³ Burn Surgery, University of Colorado Health Sciences Center, Denver, Colorado⁴

Received 11 November 2005/ Returned for modification 12 February 2006/ Accepted 21 March 2006

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 0.5 µg/ml and MICs of 1 µg/ml, respectively. However, satisfactory PTA was not obtained with less-susceptible gram-negative organisms with MICs of 1 µg/ml or any organism with a MIC of 2 µg/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 µg/ml even though they are defined as susceptible. Alternative antibiotics or treatment strategies should be considered for infections due to these pathogens.