Affiliation:
1. Departments of Pathology and Laboratory Medicine1 and
2. Medicine,2 University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4283, and
3. Department of Drug Metabolism and Pharmacokinetics, SmithKline Beecham Pharmaceuticals, The Frythe, Welwyn Herts AL6 9AR, United Kingdom3
Abstract
ABSTRACT
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 log
10
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 (AUC
0–24
) 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 AUC
0–24
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.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
24 articles.
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1. The Association of Antibiotic Treatment Regimen and Hospital Mortality in Patients Hospitalized With Legionella Pneumonia;Clinical Infectious Diseases;2015-02-25
2. Legionnaires' Disease and Pontiac Fever;Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases;2015
3. Activity In Vitro of the Quinolones;Quinolone Antimicrobial Agents;2014-04-08
4. Fastidious intracellular bacteria as causal agents of community-acquired pneumonia;Expert Review of Anti-infective Therapy;2010-07
5. Legionella;Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases;2010