title: Clarithromycin-resistant mycobacterium avium is still susceptible to treatment with clarithromycin and is virulent in mice.
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.
authors.affiliation: Kuzell Institute for Arthritis and Infectious Diseases, California Pacific Medical Center, San Francisco, California 94115, USA. luiz@cooper.cpmc.org
authors.forename: L E
authors.initials: LE
authors.lastname: Bermudez
authors.forename: K
authors.initials: K
authors.lastname: Nash
authors.forename: M
authors.initials: M
authors.lastname: Petrofsky
authors.forename: L S
authors.initials: LS
authors.lastname: Young
authors.forename: C B
authors.initials: CB
authors.lastname: Inderlied
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000382:microbiology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000627:therapeutic use; D017291:Clarithromycin / Q000494:pharmacology* / Q000627:therapeutic use; D004352:Drug Resistance, Microbial; D004977:Ethambutol / Q000627:therapeutic use; D006801:Humans; D066298:In Vitro Techniques; D008264:Macrophages / Q000187:drug effects / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D015269:Mycobacterium avium Complex / Q000187:drug effects* / Q000472:pathogenicity; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy* / Q000382:microbiology; D012338:RNA, Ribosomal, 23S / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents; D012338:RNA, Ribosomal, 23S; D004977:Ethambutol; D017291:Clarithromycin