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JAC Advance Access published online on December 19, 2003

Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh016
© 2003 by The British Society for Antimicrobial Chemotherapy
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© 2003 The British Society for Antimicrobial Chemotherapy

Original article

In vitro susceptibility of Bacillus anthracis to various antibacterial agents and their time-kill activity

A. Athamna 1 , M. Massalha 1 , M. Athamna 2 , A. Nura 1 , B. Medlej 1 , I. Ofek 3 , D. Bast 4 , and E. Rubinstein 5 *

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

* Corresponding author. E-mail: erubins{at}yahoo.com.

Received 23 June 2003 ; revised 8 October 2003 ; accepted 9 October 2003

Abstract

Objectives: To investigate the in vitro acquisition of resistance to antibiotics by Bacillus anthracis.

Methods: The in vitro activities of 18 antibacterial agents against two strains of B. anthracis, the Sterne strain and the Russian anthrax vaccine strain ST-1, were tested by determining the MICs and by measuring the rates of antibiotic kill at 5x and 10x MIC.

Results: The fluoroquinolones ciprofloxacin, ofloxacin, levofloxacin and moxifloxacin, the {beta}-lactams penicillin G and amoxicillin, the macrolide clarithromycin, the ketolide telithromycin, as well as clindamycin, rifampicin and quinupristin/dalfopristin had MICs in the range of 0.03-0.25 mg/L. Minocycline had an MIC of 0.03 mg/L, as did penicillin, against the ST-1 strain. Ciprofloxacin had an MIC of 0.03 mg/L against both strains. Erythromycin, vancomycin and the oxazolidinone linezolid were less active (MIC 0.5-2.5 mg/L). Ceftriaxone was the least active, having an MIC of 8.0 mg/L. Chloramphenicol was inactive (MIC > 256 mg/L). Quinupristin/dalfopristin, rifampicin and moxifloxacin showed the most rapid bacterial killing, achieving a complete eradication of detectable organisms (2 log10 reduction within 0.5-3 h and 4 log10 reduction within 0.5-4 h for both strains at concentrations of 5x and 10x the MIC). The {beta}-lactams and vancomycin demonstrated a 2-4 log10 reduction within 5-15 h. Ceftriaxone had a similar effect to penicillin and amoxicillin against the ST-1 strain, but a slower effect than these two {beta}-lactams against the Sterne strain. The macrolides, tetracyclines and linezolid demonstrated a lower kill rate, while chloramphenicol did not kill at all.

Conclusions: These data expand on the spectrum of agents recommended for the treatment of anthrax (ciprofloxacin, penicillin G and tetracyclines) and add new options, such as other fluoroquinolones, amoxicillin, rifampicin and quinupristin/dalfopristin, as potential therapeutic agents.

Keywords: anthrax, fluoroquinolones, macrolides, {beta}-lactams
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