Comparison of clarithromycin and ciprofloxacin therapy for Bacillus anthracis Sterne infection in mice with or without (60)Co gamma-photon irradiation.
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.
Brook
Itzhak
I
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.
Giraldo
Dianet E
DE
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.
Germana
Antonino
A
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.
Nicolau
David P
DP
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.
Jackson
William E
WE
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.
Elliott
Thomas B
TB
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.
Thakar
Jay H
JH
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.
Shoemaker
Michael O
MO
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.
Ledney
G David
GD
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.
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
D000900:Anti-Bacterial Agents; D003035:Cobalt; D002939:Ciprofloxacin; D017291:Clarithromycin