Pharmacokinetics and Pharmacodynamics of Intravenous Levofloxacin in Patients with Early-Onset Ventilator-Associated Pneumonia
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To investigate the pharmacokinetics of levofloxacin and the pharmacokinetic-pharmacodynamic appropriateness of its total body exposure in patients in the intensive care unit (ICU) treated for early-onset ventilator-associated pneumonia (VAP) with intravenous levofloxacin 500mg twice daily.
Prospective non-blinded pharmacokinetic-pharmacodynamic study.
Ten critically ill adult patients with normal renal function.
Blood and urine samples were collected at appropriate times during a 12-hour administration interval at steady state. Levofloxacin concentrations were determined by high-performance liquid chromatography. Clinical and microbiological outcomes were assessed.
Levofloxacin pharmacokinetics were only partially comparable with those obtained from literature data for healthy volunteers. Area under the concentration-time curve (AUCτ) over the 12-hour dosage interval was about 30–40)% lower than in healthy volunteers (33.90 vs 49.60 mg · h/L). The reduced exposure may be due to a greater clearance of levofloxacin (0.204 vs 0.145 L/h/kg [3.40 vs 2.42 mL/min/kg]), leading to a shorter elimination half-life (5.2 vs 7.6 hours). Cumulative urinary excretion during the 12-hour dosage interval confirmed the greater excretion of unchanged drug in these patients compared with healthy subjects (76% vs 68%). Coadministered drugs used to treat underlying diseases (dopamine, furosemide, mannitol) may at least partially account for this enhanced elimination in critically ill patients. Intravenous levofloxacin 500mg twice daily ensured a median Cmax/MIC (maximum plasma concentration/minimum inhibitory concentration) ratio of 102 and a median 24-hour AUC/MIC ratio of 930 SIT−1 · h (inverse serum inhibitory titre integrated over time) against methicillinsensitive Staphylococcus aureus and Haemophilus influenzile. The overall success rate of the assessable cases was 75% (6/8). Bacterial eradication was obtained in all of the assessable cases (8/8), but a superinfection (Acinetobacter anitratus, Pseudomonas aeruginosa) occurred in three cases.
The findings support the suitability of intravenous levofloxacin 500mg twice daily in the treatment of early-onset VAP in ICU patients with normal renal function. Levofloxacin may represent a valid alternative to non-pseudomonal β-lactams or aminoglycosides in the empirical treatment of early-onset VAP. However, further larger studies are warranted to investigate its efficacy.
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