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Antimicrobial Agents and Chemotherapy, August 2001, p. 2204-2209, Vol. 45, No. 8
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.
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
*
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.
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