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Antimicrobial Agents and Chemotherapy, January 1998, p. 180-183, Vol. 42, No. 1
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Emergence of Mycobacterium avium Populations Resistant to Macrolides during Experimental Chemotherapy

Luiz E. Bermudez,* Mary Petrofsky, Peter Kolonoski, and Lowell S. Young

Kuzell Institute for Arthritis & Infectious Diseases, California Pacific Medical Center Research Institute, San Francisco, California

Received 10 April 1997/Returned for modification 11 June 1997/Accepted 17 October 1997

Macrolide resistance is an emerging problem in AIDS patients who receive these agents for treatment or prophylaxis against Mycobacterium avium (MAC) infection. We compared the emergence of resistant MAC strains during therapy with clarithromycin (clarithromycin resistance was defined as MIC >=  32 µg/ml) and azithromycin (azithromycin resistance was defined as MIC >=  128 µg/ml) in C57BL/6 beige mice. Treatment with clarithromycin and azithromycin resulted in a decrease of 98.5% in the number of viable bacteria in spleens at week 8 and 99% at week 12 compared with the number of bacteria present in spleen before the initiation of therapy (P < 0.001). Splenic homogenates were also plated onto 7H11 agar plus clarithromycin at 32 µg/ml or azithromycin at 128 µg/ml. Resistance emerged significantly more often in mice treated with clarithromycin (100% of treated mice at both 8 and 12 weeks) than in those receiving azithromycin (0% at week 8 and 14% at week 12). The frequencies of resistance of the MAC population in the spleen to clarithromycin were 2.1 × 10-3 at week 8 and 1.1 × 10-2 at week 12, whereas resistance to azithromycin was absent at week 8 (all mice) and was ~3.5 × 10-5 (mean for the three positive animals) at week 12. Clarithromycin was more effective in initial reduction of MAC burden in tissue after 8 and 12 weeks of treatment, but resistant strains emerged significantly more frequently after treatment with clarithromycin than after treatment with azithromycin.

* Corresponding author. Mailing address: Kuzell Institute, 2200 Webster St., Suite 305, San Francisco, CA 94115. Phone: (415) 561-1734. Fax: (415) 441-8548. E-mail: luizb{at}cooper.cpmc.org.

Antimicrobial Agents and Chemotherapy, January 1998, p. 180-183, Vol. 42, No. 1
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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