MYCOBACTERIUM AVIUM COMPLEX


I. Two different species of non-tuberculous mycobacteria

II. Disseminated form

  1. Usually occurs in pts with CD4 < 100
  2. Causes constitutional sx, weight loss, and diarrhea
  3. Associated with reduced survival in PWA's

III. Prophylaxis

  1. Environmental measures may have role as pts don't acquire MAC until AIDS is advanced
  2. Chemoprophylaxis
  1. Rifabutin
  1. 2 multicenter randomized double-blind trials compared rifabutin 300mg QD with placebo. (NEJM 329:828, 1993)
  1. 1100 pts with AIDS and CD4 <200; avg. treatment duration 6.5 mos.
  2. Rifabutin group had 8% MAC bacteremia vs 17% for placebo (sig.)
  3. Also statistically sig. reduction in sx and hosps with rifabutin
  4. Nonsignificant trend toward fewer deaths with rifabutin (33 vs 47; p= 0.086)
  1. Concerns include adverse reactions (neutropenia, thrombocytopenia, GI disturbances); increased use leading to increase in rifabutin-resistant M. tuberculosis, and interactions with other drugs (e.g. increases hepatic metabolism of AZT)
  1. Clarithromycin
  1. NEJM 335:384, 1996-JW
  1. 667 pts with AIDS and CD4 < 100 randomized to clarithromycin vs. placebo (dose?)
  2. RR of MAC bacteremia over 14 mos. f/u was 0.36 with clarithromycin
  1. Azithromycin 1200mg/wk vs. rifabutin 300mg/d vs both (NEJM 335:392, 1996-JW)
  1. RR of developing MAC bacteremia was 0.50 with azithromycin compared with rifabutin
  2. RR of developing MAC bacteremia was 0.50 with both compared with azithromycin alone
  3. Combination therapy conferred no survival advantage (how long f/u?) and ass'd with 90% rate of adverse events
  1. USPHS task force report recommended rifabutin prophylaxis for HIV-infected pts with CD4 < 100 (NEJM, 329:832?, 1993); CDC recommends only when CD4 < 75 (MMWR 44:1, 1995)
  2. However, if CD4 counts start to rise with antiretroviral therapy, probably OK to stop (520 pts with CD4 counts rising to > 100 on antiretrovirals randomized to weekly axithromycin vs. placebo; over median 12mo f/u, no diff. in incidence of MAC infections or mortality (NEJM 342:1085, 2000--JW)
  1. Treatment: many drugs used, but not a lot of comparative data.
  1. Drugs in use include clarithromycin, azithromycin, rifampin, rifabutin, clofazimine, ethambutol, ciprofloxacin, amikacin; also 2 new drugs are being evaluated: levofloxacin and roxithromycin.