Pharmacokinetics and intrapulmonary diffusion of levofloxacin in critically ill patients with severe community-acquired pneumonia - PubMed (original) (raw)

Clinical Trial

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

Emmanuel Boselli et al. Crit Care Med. 2005 Jan.

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 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.

PubMed Disclaimer

Cited by

Antimicrobial Treatment and Prophylaxis of Plague: Recommendations for Naturally Acquired Infections and Bioterrorism Response.
Nelson CA, Meaney-Delman D, Fleck-Derderian S, Cooley KM, Yu PA, Mead PS; Contributors. Nelson CA, et al. MMWR Recomm Rep. 2021 Jul 16;70(3):1-27. doi: 10.15585/mmwr.rr7003a1. MMWR Recomm Rep. 2021. PMID: 34264565 Free PMC article.
Does Critical Illness Change Levofloxacin Pharmacokinetics?
Roberts JA, Cotta MO, Cojutti P, Lugano M, Della Rocca G, Pea F. Roberts JA, et al. Antimicrob Agents Chemother. 2015 Dec 14;60(3):1459-63. doi: 10.1128/AAC.02610-15. Antimicrob Agents Chemother. 2015. PMID: 26666946 Free PMC article.
Should patients with acute exacerbation of chronic bronchitis be treated with antibiotics? Advantages of the use of fluoroquinolones.
Mensa J, Trilla A. Mensa J, et al. Clin Microbiol Infect. 2006 May;12 Suppl 3(Suppl 3):42-54. doi: 10.1111/j.1469-0691.2006.01396.x. Clin Microbiol Infect. 2006. PMID: 16669928 Free PMC article. Review.
Bench-to-bedside review: Appropriate antibiotic therapy in severe sepsis and septic shock--does the dose matter?
Pea F, Viale P. Pea F, et al. Crit Care. 2009;13(3):214. doi: 10.1186/cc7774. Epub 2009 Jun 10. Crit Care. 2009. PMID: 19519961 Free PMC article. Review.
Mini-broncho-alveolar lavage: a simple and promising method for assessment of antibiotic concentration in epithelial lining fluid.
Mimoz O, Dahyot-Fizelier C. Mimoz O, et al. Intensive Care Med. 2007 Sep;33(9):1495-7. doi: 10.1007/s00134-007-0689-9. Epub 2007 Jun 27. Intensive Care Med. 2007. PMID: 17594075 No abstract available.

Pharmacokinetics and intrapulmonary diffusion of levofloxacin in critically ill patients with severe community-acquired pneumonia - PubMed (original) (raw)