1887

Abstract

Biological agents and ionizing radiation lead to more severe clinical outcomes than either insult alone. This study investigated the survival of non-irradiated and Co-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 × 10 c.f.u. of Sterne spores 4 days after the non-lethal 7 Gy dose of Co gamma radiation. Twenty-one days of treatment with CLR/14-OH CLR, 150 mg kg twice daily, or CIP, 16.5 mg kg 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 ( < 0.001). Sterne only was isolated from 25–50 % of treated mice with or without irradiation. Mixed infections with Sterne were present in 50–71 % of gamma-irradiated mice but only in 5–10 % of mice without irradiation.

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2005-12-01
2020-10-27
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