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Antimicrobial Agents and Chemotherapy, August 2001, p. 2204-2209, Vol. 45, No. 8
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.8.2204-2209.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

In Vitro Activity of Gemifloxacin (SB-265805, LB20304a) against Legionella pneumophila and Its Pharmacokinetics in Guinea Pigs with L. pneumophila Pneumonia

Paul H. Edelstein,1,2,* Takashi Shinzato,1 Edward Doyle,3 and Martha A. C. Edelstein1

Departments of Pathology and Laboratory Medicine1 and Medicine,2 University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4283, and Department of Drug Metabolism and Pharmacokinetics, SmithKline Beecham Pharmaceuticals, The Frythe, Welwyn Herts AL6 9AR, United Kingdom3

Received 29 November 2000/Returned for modification 27 March 2001/Accepted 27 April 2001

The activity of gemifloxacin against intracellular Legionella pneumophila and for the treatment of guinea pigs with L. pneumophila pneumonia was studied. Gemifloxacin, azithromycin, and levofloxacin (1 µg/ml) reduced bacterial counts of two L. pneumophila strains grown in guinea pig alveolar macrophages by 2 to 3 log10 units. Gemifloxacin and levofloxacin had roughly equivalent intracellular activities. In contrast, erythromycin had static activity only. Therapy studies of gemifloxacin, azithromycin, and levofloxacin were performed in guinea pigs with L. pneumophila pneumonia. When gemifloxacin (10 mg/kg) was given by the intraperitoneal (i.p.) route to infected guinea pigs, mean peak levels in plasma were 1.3 µg/ml at 0.5 h and 1.2 µg/ml at 1 h postinjection. The terminal half-life phase of elimination from plasma was 1.3 h, and the area under the concentration-time curve from 0 to 24 h (AUC0-24) was 2.1 µg · h/ml. For the same drug dose, mean levels in lungs were 3.4 µg/g at both 0.5 and 1 h, with a half-life of 1.5 h and an AUC0-24 of 6.0 µg · h/ml. All 15 L. pneumophila-infected guinea pigs treated with gemifloxacin (10 mg/kg/dose given i.p. once daily) for 2 days survived for 9 days after antimicrobial therapy, as did 13 of 14 guinea pigs treated with the same dose of gemifloxacin given for 5 days. All 12 azithromycin-treated animals (15 mg/kg/dose given i.p. once daily for 2 days) survived, as did 11 of 12 animals treated with levofloxacin (10 mg/kg/dose given i.p. once daily for 5 days). None of 12 animals treated with saline survived. Gemifloxacin is effective against L. pneumophila in infected macrophages and in a guinea pig model of Legionnaires' disease, even with an abbreviated course of therapy. These data support studies of the clinical effectiveness of gemifloxacin for the treatment of Legionnaires' disease.


* Corresponding author. Mailing address: Clinical Microbiology Laboratory, 4 Gates, Hospital of the University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104-4283. Phone: (215) 662-6651. Fax: (215) 662-6655. E-mail: phe{at}mail.med.upenn.edu.


Antimicrobial Agents and Chemotherapy, August 2001, p. 2204-2209, Vol. 45, No. 8
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.8.2204-2209.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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