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JAC Advance Access originally published online on June 17, 2004
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Journal of Antimicrobial Chemotherapy 2004 54(2):424-428; doi:10.1093/jac/dkh258
JAC vol.54 no.2 © The British Society for Antimicrobial Chemotherapy 2004; all rights reserved.

Selection of Bacillus anthracis isolates resistant to antibiotics

A. Athamna1, M. Athamna1,2, N. Abu-Rashed1, B. Medlej1, D. J. Bast3 and E. Rubinstein2,4,*

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

* Correspondence address. Infectious Diseases Unit, Sheba Medical Center, Tel-Aviv University School of Medicine, Tel Hashomer 52621, Israel. Tel: +972-3-5345-389; Fax: +972-3-5303-501; Email: erubins{at}yahoo.com

Objective: Long-term therapy for anthrax might induce antimicrobial resistance in Bacillus anthracis. The aim of the present study was to investigate the potential of 18 different antibiotics to select resistant isolates of B. anthracis, (ST-1 and Sterne strains).

Methods: Resistant isolates were selected by serial passages on brain heart infusion agar containing increasing concentrations of antibiotics (from the MIC upwards).

Results: The MICs of ciprofloxacin, ofloxacin and levofloxacin increased from 0.125–0.25 to 8 mg/L, that of moxifloxacin increased from 0.03–0.06 to 8 mg/L, in both strains, and the MIC of garenoxacin increased from 0.015 to 0.5 mg/L for the ST-1 strain and from 0.03 to 8 mg/L for the Sterne strain. The MICs of tetracycline and minocycline increased from 0.125 to 2–8 mg/L and 0.06 to 1 mg/L, respectively. The MIC of vancomycin increased from 2.5 to 20 mg/L for the ST-1 strain and from 5 to 20 mg/L for the Sterne strain. Linezolid exhibited an MIC increase from 2 to 4 mg/L for both strains. The MIC of quinupristin/dalfopristin increased from 0.125 to 64–128 mg/L. Erythromycin demonstrated an MIC increase from 1 to 128 mg/L, that of clarithromycin increased from 0.125 to 8–64 mg/L and that of telithromycin increased from 0.06–0.125 to 1–4 mg/L. The clindamycin MIC increased from 0.125–0.25 to 8 mg/L. Penicillin G and amoxicillin MICs increased from <1 mg/L to 128–512 mg/L. Isolates made resistant to one fluoroquinolone exhibited cross-resistance to the other quinolones except the ST-1 mutant strain which remained susceptible to garenoxacin. Cross-resistance to fluoroquinolones did not correlate with resistance to other antibiotics.

Conclusion: The ease with which B. anthracis can be made resistant in vitro suggests that close monitoring of patients treated for anthrax is mandatory.

Keywords: anthrax , quinolones , macrolides , cross-resistance


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