Antimicrobial therapy for Bacillus anthracis-induced polymicrobial infection in 60Co γ-irradiated mice

Challenge with both nonlethal ionizing radiation and toxigenic Bacillus anthracis spores increases the rate of mortality from a mixed bacterial infection. If biological weapons, such as B. anthracis spores, and nuclear weapons were used together, casualties could be more severe than they would be from the use of either weapon alone. We previously discovered that a polymicrobial infection developed in B6D2F(1)/J mice after nonlethal (7-Gy) Co-60 gamma irradiation and intratracheal challenge with B. anthracis Sterne spores 4 days after irradiation. In this present study, we investigated the survival of mice and the response of the polymicrobial infection during the course of antimicrobial therapy with penicillin G procaine, ofloxacin, trovafloxacin, or gatifloxacin. Survival was prolonged, but not ensured, when the mice were treated with either broad-spectrum ofloxacin or narrow-spectrum penicillin G for 7 days beginning 6 or 24 h after challenge. Survival was not prolonged when therapy was delayed more than 24 h after challenge. When these two antimicrobial agents were given for 21 days, the survival rate was increased from 0% for the controls to 38 to 63% after therapy. Therapy with trovafloxacin or gatifloxacin reduced the incidence of mixed infection and improved the rate of survival to 95% (trovafloxacin) or 79% (gatifloxacin), whereas the rate of survival for the controls was 5%. We conclude that the mixed infection induced by B. anthracis in irradiated mice complicates effective therapy with a single antimicrobial agent. To limit mortality following nonlethal irradiation and challenge with B. anthracis spores, antimicrobial therapy needs to be initiated within a few hours after challenge and continued for up to 21 days.