title: Efficacy of macrolides and telithromycin against leptospirosis in a hamster model.
abstract: Human studies support the use of beta-lactams and tetracyclines in the treatment of leptospirosis. Additional agents from these and other classes of antimicrobials also have in vitro activity against Leptospira species, though corroborating in vivo data are limited or lacking. We evaluated the therapeutic efficacy of azithromycin, clarithromycin, and telithromycin in a lethal hamster model of leptospirosis using Leptospira interrogans serogroup Canicola serovar Portlandvere. A range of dosages for each antimicrobial was given to the infected animals on days 2 through 7 (5 days) of the 21-day survival model. All untreated control animals survived less than 10 days from infection. Ninety to 100% of doxycycline controls, treated for 5 days with 5 mg/kg of body weight of drug, survived to 21 days. Treatment with azithromycin (daily dose: 6.25, 12.5, 25, 50, 100, or 200 mg/kg) resulted in 100% survival at all evaluated doses. Animals receiving 20 mg/kg or more of clarithromycin (daily dose: 1, 5, 10, 15, 20, 40, 60, or 100 mg/kg) had improved survival. Ninety-eight percent of animals treated with telithromycin (daily dose: 1, 5, 10, 15, 20, or 40 mg/kg) survived. We conclude that all agents tested have demonstrated in vivo efficacy in treating acute leptospirosis. These results provide support for further evaluation of macrolide and ketolide antimicrobial agents in human trials.
authors.affiliation: Department of Medicine, Brooke Army Medical Center, Fort Sam Houston, Texas 78234, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Moon
authors.forename: Michael W
authors.initials: MW
authors.lastname: Ellis
authors.forename: Michael C
authors.initials: MC
authors.lastname: Ellis
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Griffith
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Hawley
authors.forename: Robert G
authors.initials: RG
authors.lastname: Rivard
authors.forename: Suzanne
authors.initials: S
authors.lastname: McCall
authors.forename: Duane R
authors.initials: DR
authors.lastname: Hospenthal
authors.forename: Clinton K
authors.initials: CK
authors.lastname: Murray
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology; D017291:Clarithromycin / Q000494:pharmacology; D006224:Cricetinae; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000494:pharmacology; D005260:Female; D048628:Ketolides / Q000494:pharmacology*; D007921:Leptospira interrogans / Q000145:classification / Q000187:drug effects; D007922:Leptospirosis / Q000188:drug therapy* / Q000401:mortality; D018942:Macrolides / Q000494:pharmacology*; D008647:Mesocricetus; D012703:Serotyping; D013045:Species Specificity; D016019:Survival Analysis
chemical_list: D000900:Anti-Bacterial Agents; D048628:Ketolides; D018942:Macrolides; D017963:Azithromycin; D017291:Clarithromycin; C106791:telithromycin; D004318:Doxycycline