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Antimicrobial Agents and Chemotherapy, August 2001, p. 2210-2214, Vol. 45, No. 8
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.8.2210-2214.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Telithromycin Is Active against Mycobacterium avium in Mice despite Lacking Significant Activity in Standard In Vitro and Macrophage Assays and Is Associated with Low Frequency of Resistance during Treatment

Luiz E. Bermudez,1,* Clark B. Inderlied,2,3 Peter Kolonoski,1 Martin Wu,1 Priscilla Aralar,2 and Lowell S. Young1

Kuzell Institute for Arthritis and Infectious Diseases, San Francisco, California,1 and Department of Pathology, Children's Hospital of Los Angeles,2 and University of Southern California,3 Los Angeles, California

Received 17 July 2000/Returned for modification 29 December 2000/Accepted 3 May 2001

The activity of telithromycin, a new ketolide, was evaluated in vitro and in vivo against Mycobacterium avium complex (MAC) strains. The MIC of telithromycin for several M. avium isolates obtained from the blood of AIDS patients ranged from 16 to >128 µg/ml (MIC at which 90% of isolates are inhibited, >128 µg/ml), and the compound did show activity in the macrophage system at concentrations greater than 8 or 16 µg/ml, but this was dependent on the MAC strain used. Telithromycin was then administered to mice infected with MAC strain 101 for 4 weeks at doses of 100, 200, or 400 mg/kg of body weight/day. Treatment with 100 and 200 mg/kg/day was bacteriostatic, but at 400 mg/kg/day telithromycin was bactericidal for MAC strains. The frequency of the emergence of resistance to telithromycin was low despite prolonged usage (12 weeks). This study demonstrates that telithromycin is active in vivo against MAC and warrants further evaluation.

* Corresponding author. Mailing address: Kuzell Institute, 2200 Webster St., Suite 305, San Francisco, CA 94115. Phone: (415) 561-1734. Fax: (415) 441-8548.

Antimicrobial Agents and Chemotherapy, August 2001, p. 2210-2214, Vol. 45, No. 8
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.8.2210-2214.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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