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Is In Vitro Antibiotic Combination More Effective than Single-Drug Therapy against Anthrax?

Triangle Research And Development Center, Kfar-Qaraa,¹ Department Of Human Microbiology, Tel Aviv University School of Medicine, Tel Aviv,⁵ Infectious Diseases Unit, Sheba Medical Center, Tel Aviv University School of Medicine, Tel Hashomer, Israel,² Toronto Centre for Antimicrobial Research and Evaluation, Department of Microbiology, Mount Sinai Hospital, Toronto, Ontario, Canada,³ GR Micro, London, United Kingdom⁴

Received 2 June 2004/ Returned for modification 9 August 2004/ Accepted 8 November 2004

Antibiotic combinations are used to enhance antibacterial efficacy and to prevent the development of resistance. We have tested a possible synergistic effect of several antibacterial combinations on Bacillus anthracis. The in vitro activities of antibiotic combinations against two strains of B. anthracis, strain Sterne and the Russian anthrax vaccine strain STi, were tested by the fractional inhibitory concentration (FIC) method, derived from the MICs of the agents in combination, and by measuring the rate of bacterial killing over time by several antibiotic combinations. The FIC results showed that synergism against both B. anthracis strains was observed only with the combination of rifampin and clindamycin. The telithromycin-amoxicillin combination showed synergism against strain Sterne only. All other combinations were either indifferent or antagonistic. The results of the bacterial time-kill study demonstrated indifferent effects for all combinations. These in vitro results demonstrate the difficulties in obtaining synergistic combinations of antibiotics against B. anthracis.

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