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J Med Microbiol 54 (2005), 1157-1162; DOI: 10.1099/jmm.0.46166-0
© 2005 Society for General Microbiology
ISSN 0022-2615

Comparison of clarithromycin and ciprofloxacin therapy for Bacillus anthracis Sterne infection in mice with or without 60Co gamma-photon irradiation

Itzhak Brook1, Dianet E Giraldo1, Antonino Germana1, David P Nicolau2, William E Jackson1, Thomas B Elliott1, Jay H Thakar1, Michael O Shoemaker1 and G David Ledney1

1Scientific Research Department, Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603, USA 2Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT 06074, USA

Correspondence Itzhak Brook Brook{at}afrri.usuhs.mil

Received 20 May 2005
Accepted 3 August 2005

Biological agents and ionizing radiation lead to more severe clinical outcomes than either insult alone. This study investigated the survival of non-irradiated and 60Co-gamma-irradiated mice given therapy for inhalation anthrax with ciprofloxacin (CIP) or a clinically relevant mixture of clarithromycin (CLR) and its major human microbiologically important metabolite 14-hydroxy clarithromycin (14-OH CLR). All B6D2F1/J 10-week-old female mice were inoculated intratracheally with 3 x 108 c.f.u. of Bacillus anthracis Sterne spores 4 days after the non-lethal 7 Gy dose of 60Co gamma radiation. Twenty-one days of treatment with CLR/14-OH CLR, 150 mg kg–1 twice daily, or CIP, 16.5 mg kg–1 twice daily, began 24 h after inoculation. Pharmacokinetics indicate that the area under the curve (AUC) for 14-OH CLR on the concentration-versus-time graph was slightly higher in gamma-irradiated than non-irradiated animals. Neither drug was able to increase survival in gamma-irradiated animals. CIP and CLR/14-OH CLR therapies in non-irradiated animals increased survival from 49 % (17/35 mice) in buffer-treated animals to 94 % (33/35) and 100 %, respectively (P < 0.001). B. anthracis Sterne only was isolated from 25–50 % of treated mice with or without irradiation. Mixed infections with B. anthracis Sterne were present in 50–71 % of gamma-irradiated mice but only in 5–10 % of mice without irradiation.

Abbreviations: AUC, area under the curve; CIP, ciprofloxacin; CLR, clarithromycin; CLR/14-OH, CLR plus metabolite; i.t., intratracheal(ly); 14-OH CLR, 14-hydroxy clarithromycin.






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