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Background:  Acquisition of macrolide resistance clearly occurs during treatment of HIV-related disseminated Mycobacterium avium complex (MAC) infection. Recently, we noted an increase in macrolide resistance in initial HIV-related MAC isolates.

Methods:  Retrospective review of HIV-infected persons with MAC isolates from normally sterile anatomic sites from 1989 to 2004, with detailed cohort analysis to assess predictors of initial isolate macrolide resistance between 1997 and 2004. Macrolide susceptibility testing was performed at the time of initial culture using disk diffusion, a method previously validated in our lab. Adherence to MAC prophylaxis was assessed using pharmacy data.

Results:  Since 1996, there has been a marked decrease in the incidence of HIV-related MAC infections (see the graph). From 1997 to 2004, there were 51 HIV-infected persons with sterile site MAC isolates, or approximately 7 cases per year:  38 of 51 (75%) were isolated from blood; 11 of 51 (22%) represented immune reconstitution events; and 8 of 51 (16%) initial isolates had macrolide resistance. The rate of resistance increased steadily from 0% before 1996, to 12% in 1997–1998, and to 36% in 2003–2004:  3 of 8 (38%) initially resistant isolates arose in patients with a history of prior MAC treatment versus 1 of 43 (2%) susceptible isolates (p < 0.001); 2 of 8 (25%) resistant isolates occurred during MAC prophylaxis with a macrolide versus 14 of 43 (33%) susceptible isolates (p = 0.67). Median adherence to macrolide prophylaxis was 74% in patients with resistant isolates versus 79% in patients with susceptible isolates (p = 0.54); and 3 of 8 (38%) resistant isolates had no prior history of MAC infection and were not receiving prophylaxis with clarithromycin or azithromycin.

Conclusions:  The incidence of MAC infections in HIV-infected persons has decreased dramatically, but primary macrolide resistance is increasingly common. Resistant MAC was more common in persons with a prior history of treated MAC infection; however 38% of resistant isolates had no identifiable risk for resistance. Initial MAC isolates in HIV infected persons should routinely be tested for macrolide resistance.

Keywords: Mycobacterium avium complex; macrolide resistance; HIV