Clindamycin and quinolone therapy for Bacillus anthracis Sterne infection in 60Co-gamma-photon-irradiated and sham-irradiated mice.
OBJECTIVE
Sublethal ionizing doses of radiation increase the susceptibility of mice to Bacillus anthracis Sterne infection. In this study, we investigated the efficacy of clindamycin in 60Co-gamma-photon-irradiated and sham-irradiated mice after intratracheal challenge with B. anthracis Sterne spores. Clindamycin has in vitro activity against B. anthracis and inhibits the production of toxin from other species, although no direct evidence exists that production of B. anthracis toxin is inhibited.


METHODS
Ten-week-old B6D2F1/J female mice were either sham-irradiated or given a sublethal 7 Gy dose of 60Co-gamma-photon radiation 4 days prior to an intratracheal challenge with toxigenic B. anthracis Sterne spores. Mice were treated twice daily with 200 mg/kg clindamycin (subcutaneous or oral), 100 mg/kg moxifloxacin (oral), 50 mg/kg ciprofloxacin (subcutaneous) or a combination therapy (clindamycin + ciprofloxacin). Bacteria were isolated and identified from lung, liver and heart blood at five timed intervals after irradiation. Survival was recorded twice daily following intratracheal challenge.


RESULTS
The use of clindamycin increased survival in gamma-irradiated and sham-irradiated animals challenged with B. anthracis Sterne in comparison with control mice (P < 0.001). Ciprofloxacin-treated animals had higher survival compared with clindamycin-treated animals in two experiments, and less survival in a third experiment, although differences were not statistically significant. Moxifloxacin was just as effective as clindamycin. Combination therapy did not improve survival of sham-irradiated animals and significantly decreased survival among gamma-irradiated animals (P = 0.01) in comparison with clindamycin-treated animals. B. anthracis Sterne was isolated from lung, liver and heart blood, irrespective of the antimicrobial treatment.


CONCLUSIONS
Treatment with clindamycin, ciprofloxacin or moxifloxacin increased survival in sham-irradiated and gamma-irradiated animals challenged intratracheally with B. anthracis Sterne spores. However, the combination of clindamycin and ciprofloxacin increased mortality associated with B. anthracis Sterne infection, particularly in gamma-irradiated animals.
Brook
I
I
Scientific Research Department, Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603, USA. ib6@georgetown.edu
Germana
A
A
Giraldo
D E
DE
Camp-Hyde
T D
TD
Bolduc
D L
DL
Foriska
M A
MA
Elliott
T B
TB
Thakar
J H
JH
Shoemaker
M O
MO
Jackson
W E
WE
Ledney
G D
GD
D000284:Administration, Oral; D000818:Animals; D000881:Anthrax / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001372:Aza Compounds / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001408:Bacillus anthracis / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D001769:Blood / Q000382:microbiology; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002981:Clindamycin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D024841:Fluoroquinolones; D005720:Gamma Rays; D007279:Injections, Subcutaneous; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000382:microbiology; D051379:Mice; D000077266:Moxifloxacin; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011833:Radiation Injuries, Experimental / Q000150:complications*; D016019:Survival Analysis
D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D002981:Clindamycin; D002939:Ciprofloxacin; D000077266:Moxifloxacin