Clarithromycin-resistant mycobacterium avium is still susceptible to treatment with clarithromycin and is virulent in mice.

TitleClarithromycin-resistant mycobacterium avium is still susceptible to treatment with clarithromycin and is virulent in mice.
Publication TypeJournal Article
Year of Publication2000
AuthorsBermudez LE, Nash K, Petrofsky M, Young LS, Inderlied CB
JournalAntimicrobial agents and chemotherapy
Volume44
Issue10
Pagination2619-22
Date Published2000 Oct
ISSN0066-4804
KeywordsAIDS-Related Opportunistic Infections, Animals, Anti-Bacterial Agents, Antitubercular Agents, Clarithromycin, Drug Resistance, Microbial, Ethambutol, Humans, Macrophages, Mice, Mice, Inbred C57BL, Microbial Sensitivity Tests, Mycobacterium avium Complex, Mycobacterium avium-intracellulare Infection, RNA, Ribosomal, 23S
Abstract

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, > or =128 microg/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.

Alternate JournalAntimicrob. Agents Chemother.