A comparison of two regimens for the treatment of Mycobacterium avium complex bacteremia in AIDS: rifabutin, ethambutol, and clarithromycin versus rifampin, ethambutol, clofazimine, and ciprofloxacin. Canadian HIV Trials Network Protocol 010 Study Group

N Engl J Med. 1996 Aug 8;335(6):377-83. doi: 10.1056/NEJM199608083350602.


Background: Bacteremia with the Mycobacterium avium complex is common in patients with the acquired immunodeficiency syndrome (AIDS), but the most effective treatment for this infection remains unclear.

Methods: We randomly assigned 229 patients with AIDS and M. avium complex bacteremia to receive either rifampin (600 mg daily), ethambutol (approximately 15 mg per kilogram of body weight daily), clofazimine (100 mg daily), and ciprofloxacin (750 mg twice daily) (the four-drug group) or rifabutin (600 mg daily), ethambutol (as above), and clarithromycin (1000 mg twice daily) (the three-drug group). In the three-drug group the dose of rifabutin was reduced by half after 125 patients were randomized, because 24 of 63 patients had uveitis.

Results: Among 187 patients who could be evaluated, blood cultures became negative more often in the three-drug group than in the four-drug group (69 percent vs. 29 percent, P<0.001). Among patients treated for at least four weeks, the bacteremia resolved more frequently in the three-drug group (78 percent vs. 40 percent, P<0.001). In the three-drug group, bacteremia resolved more often with the 600-mg dose of rifabutin than with the 300-mg dose (P=0.025), but the latter regimen was more effective than the four-drug regimen (P<0.05). The median survival was 8.6 months in the three-drug group and 5.2 months in the four-drug group (P = 0.001). The median Karnofsky performance score was higher in the three-drug group than in the four-drug group from week 2 to week 16 (P<0.05). Mild uveitis developed in 3 of the 53 patients receiving the 300-mg dose of rifabutin, an incidence about one quarter that observed with the 600-mg dose (P<0.001).

Conclusions: In patients with AIDS and M. avium complex bacteremia, treatment with the three-drug regimen of rifabutin, ethambutol, and clarithromycin leads to resolution of the bacteremia more frequently and more rapidly than treatment with rifampin, ethambutol, clofazimine, and ciprofloxacin, and survival rates are better.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS-Related Opportunistic Infections / drug therapy*
  • AIDS-Related Opportunistic Infections / microbiology
  • AIDS-Related Opportunistic Infections / mortality
  • Adult
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / therapeutic use*
  • Antitubercular Agents / therapeutic use*
  • Bacteremia / drug therapy*
  • Bacteremia / microbiology
  • Bacteremia / mortality
  • Ciprofloxacin / therapeutic use
  • Clarithromycin / therapeutic use
  • Clofazimine / therapeutic use
  • Drug Therapy, Combination
  • Ethambutol / therapeutic use
  • Female
  • Humans
  • Male
  • Mycobacterium avium Complex / isolation & purification
  • Mycobacterium avium-intracellulare Infection / drug therapy*
  • Mycobacterium avium-intracellulare Infection / microbiology
  • Mycobacterium avium-intracellulare Infection / mortality
  • Rifabutin / adverse effects
  • Rifabutin / therapeutic use
  • Rifampin / therapeutic use
  • Survival Analysis
  • Treatment Outcome
  • Uveitis / chemically induced


  • Anti-Bacterial Agents
  • Antitubercular Agents
  • Rifabutin
  • Ciprofloxacin
  • Ethambutol
  • Clofazimine
  • Clarithromycin
  • Rifampin