Pharmacokinetics and intrapulmonary diffusion of levofloxacin in critically ill patients with severe community-acquired pneumonia
Abstract
OBJECTIVE: To determine the steady-state plasma and epithelial lining fluid concentrations of intravenous levofloxacin, 500 mg, administered once or twice daily in critically ill patients with severe community-acquired pneumonia. DESIGN: Prospective, open-label study. SETTING: An intensive care unit and a clinical pharmacokinetic laboratory in two university hospitals. PATIENTS: Twenty-four adult patients with severe community-acquired pneumonia and receiving mechanical ventilation were enrolled. INTERVENTIONS: All subjects received 1-hr intravenous infusions of 500 mg levofloxacin once or twice daily. The plasma and epithelial lining fluid levofloxacin concentrations were determined at steady-state after 2 days of therapy with high-performance liquid chromatography. MEASUREMENTS AND MAIN RESULTS: The median (interquartile range [IQR]) plasma and epithelial lining fluid peak levofloxacin concentrations were 12.6 (IQR, 12.0-14.1) and 11.9 (IQR, 8.7-13.7) mg/L, respectively, in the once-daily group and 19.7 (IQR, 19.0-22.0) and 17.8 (IQR, 16.2-23.5) mg/L in the twice-daily group, showing a pulmonary percentage penetration of >100% in both groups. The median (IQR) total body exposures were 151 (IQR, 137-174) and 416 (IQR, 406-472) mg.hr/L, respectively, in the once-daily and twice-daily groups. CONCLUSIONS: Our results suggest that in critically ill patients who are receiving mechanical ventilation and have severe community-acquired pneumonia and creatinine clearance of >40…
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Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
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