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Antimicrobial Agents and Chemotherapy, October 2000, p. 2619-2622, Vol. 44, No. 10
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Clarithromycin-Resistant Mycobacterium avium Is Still Susceptible to Treatment with Clarithromycin and Is Virulent in Mice

Luiz E. Bermudez,1,* Kevin Nash,2 Mary Petrofsky,1 Lowell S. Young,1 and Clark B. Inderlied2,3

Kuzell Institute for Arthritis and Infectious Diseases, California Pacific Medical Center, San Francisco,1 and Children's Hospital2 and University of Southern California,3 Los Angeles, California

Received 6 January 2000/Returned for modification 30 April 2000/Accepted 26 June 2000

Resistance to clarithromycin in breakthrough Mycobacterium avium complex (MAC) isolates typically occurs 3 to 4 months after the initiation of monotherapy in bacteremic AIDS patients. It has been suggested that continuation of clarithromycin therapy still results in clinical and microbiological improvement. To study this paradox, C57BL/6 beige mice were infected with a clarithromycin-resistant (MIC, >= 128 µg/ml) strain of MAC 101 (CLA-R MAC 101) and treated with 200 mg of clarithromycin per kg of body weight/day alone or in combination with ethambutol (100 mg/kg/day) for 2 weeks. Mice infected with a clarithromycin-susceptible strain of MAC 101 had bacterial loads reduced by 90% in the liver and 91% in the spleen (P < 0.05, compared with the control). Clarithromycin treatment of CLA-R MAC 101 resulted in a 65% reduction of bacterial loads in the liver (P = 0.009) and a 71% reduction in the spleen (P = 0.009), compared with the results for the untreated control. CLA-R MAC 101 and MAC 101 (isogenic strains) had comparable growth rates in murine tissue, ruling out a loss of virulence of CLA-R MAC 101. Strains of MAC currently defined as macrolide resistant may still respond to treatment with an agent such as clarithromycin within infected tissues.

* 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: luiz{at}cooper.cpmc.org.

Antimicrobial Agents and Chemotherapy, October 2000, p. 2619-2622, Vol. 44, No. 10
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

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