title: Comparison of clarithromycin and ciprofloxacin therapy for Bacillus anthracis Sterne infection in mice with or without (60)Co gamma-photon irradiation.
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 (60)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 x 10(8) c.f.u. of Bacillus anthracis Sterne spores 4 days after the non-lethal 7 Gy dose of (60)Co 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.
authors.affiliation: Scientific 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.
authors.forename: Itzhak
authors.initials: I
authors.lastname: Brook
authors.affiliation: Scientific 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.
authors.forename: Dianet E
authors.initials: DE
authors.lastname: Giraldo
authors.affiliation: Scientific 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.
authors.forename: Antonino
authors.initials: A
authors.lastname: Germana
authors.affiliation: Scientific 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.
authors.forename: David P
authors.initials: DP
authors.lastname: Nicolau
authors.affiliation: Scientific 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.
authors.forename: William E
authors.initials: WE
authors.lastname: Jackson
authors.affiliation: Scientific 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.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Elliott
authors.affiliation: Scientific 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.
authors.forename: Jay H
authors.initials: JH
authors.lastname: Thakar
authors.affiliation: Scientific 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.
authors.forename: Michael O
authors.initials: MO
authors.lastname: Shoemaker
authors.affiliation: Scientific 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.
authors.forename: G David
authors.initials: GD
authors.lastname: Ledney
mesh_terms: D000818:Animals; D000881:Anthrax / Q000188:drug therapy* / Q000532:radiotherapy*; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002939:Ciprofloxacin / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017291:Clarithromycin / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003035:Cobalt; D004359:Drug Therapy, Combination; D005260:Female; D005720:Gamma Rays; D051379:Mice
chemical_list: D000900:Anti-Bacterial Agents; D003035:Cobalt; D002939:Ciprofloxacin; D017291:Clarithromycin