Pharmacokinetics and intrapulmonary diffusion of levofloxacin in critically ill patients with severe community-acquired pneumonia.
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.


METHODS
Prospective, open-label study.


METHODS
An intensive care unit and a clinical pharmacokinetic laboratory in two university hospitals.


METHODS
Twenty-four adult patients with severe community-acquired pneumonia and receiving mechanical ventilation were enrolled.


METHODS
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.


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 mL/min, the administration of 500 mg of intravenous levofloxacin once and twice daily allows for the exceeding of pharmacodynamic thresholds predictive of outcome (i.e., peak concentration to minimum inhibitory concentration ratio of >10 or area under concentration-time curve to minimal inhibitory concentration ratio of >125 hrs) both in serum and epithelial lining fluid for pathogens with minimum inhibitory concentration values of < or =1 mg/L and >1 mg/L, respectively.
Boselli
Emmanuel
E
Department of Anesthesiology and Intensive Care, Hôtel-Dieu Hospital, Lyon, France.
Breilh
Dominique
D
Rimmelé
Thomas
T
Djabarouti
Sarah
S
Saux
Marie-Claude
MC
Chassard
Dominique
D
Allaouchiche
Bernard
B
D000368:Aged; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002199:Capillary Permeability / Q000502:physiology; D017714:Community-Acquired Infections / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D003404:Creatinine / Q000097:blood; D003422:Critical Care; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D017052:Hospital Mortality; D006801:Humans; D007262:Infusions, Intravenous; D064704:Levofloxacin; D008168:Lung / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology; D008875:Middle Aged; D015242:Ofloxacin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018410:Pneumonia, Bacterial / Q000097:blood* / Q000188:drug therapy / Q000401:mortality
D000900:Anti-Bacterial Agents; D064704:Levofloxacin; D015242:Ofloxacin; D003404:Creatinine