Anthrax has recently been the focus of attention as a potential biological warfare agent. The therapy and prophylaxis of anthrax require vaccination combined with prolonged antibacterial therapy. It is important to examine if antibiotic combinations might shorten the 60-day period recommended for postexposure prophylaxis by providing a more radical and rapid killing of the vegetative anthrax forms and thus reducing the infective load (5). Of equal interest is the question whether combinations might reduce the risk for the development of resistance by Bacillus anthracis. During the last bioterror attack in the United States, in 2001, many individuals received antibiotic combinations as therapy and as postexposure prophylaxis (6). Clindamycin was often used based on the assumption that it might decrease the production of bacterial toxins and thus diminish the severity of disease manifestations (3).The aim of the present study was to investigate possible interactions among several antibiotics potentially effective against B. anthracis.
MATERIALS AND METHODSAntibacterial agents. The antibiotics tested in this study were as follows: ciprofloxacin and moxifloxacin (Bayer, Leverkusen, Germany), tetracycline (Sigma, Rehovot, Israel), penicillin G (Rafa Laboratories, Jerusalem, Israel), amoxicillin (GSK, Petach Tiqva, Israel), vancomycin (Eli Lilly, Sesto Fiorentino, Italy), clarithromycin (Abbott, Promedico, Petch-Tiqva, Israel), telithromycin and quinupristin-dalfopristin (Q-D) (Aventis, Paris, France), clindamycin and linezolid [Pharmacia (Agis), Bnei Braq, Israel, and Pharmacia, Kalamazoo, Mich.], and rifampin (Sigma).Penicillin G, vancomycin, rifampin, clindamycin, linezolid, and Q-D were received as dry laboratory powders and were dissolved in phosphate-buffered saline (pH 7.2). Amoxicillin was dissolved in distilled water. Clarithromycin was dissolved in analytical-grade acetone, while telithromycin and tetracycline were dissolved initially in 2 drops of acetic acid and ethanol (100%), respectively, and all three of these antibiotics were subsequently diluted in distilled water to the required concentration; at the final concentrations used, these solvents had no demonstrable antibacterial activity. Prepared solutions were frozen in small aliquots and thawed before use. Antibiotic solutions were sterilized through 0.45-m-pore-size filters (Millipore S.A., Paris, France). Moxifloxacin and ciprofloxacin were obtained as injectable solutions. Bacterial strains and growth conditions. The bacteria used in this study were two strains of B. anthracis: strain Sterne (a gift from the Colorado Serum Institute, Denver, Colo.) and the Russian strain STi, purchased in Moscow, Russia. Neither strain is a human pathogen, because both lack the plasmid necessary to produce the capsule of the vegetative form, which is necessary for human pathogenicity. Bacterial spores were stored in sterile 30% glycerol in phosphate-buffered saline and were spread on brain heart infusion (BHI) agar (Difco Laboratories, Detroit, Mich.) and incubate...