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Previous Volume 335:377-384 August 8, 1996 Number 6 Next

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ABSTRACT

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.

Source Information

From the Division of Infectious Diseases, Department of Medicine, University of Alberta, Edmonton (S.D.S.); the National Centre, Canadian HIV Trials Network, Vancouver, B.C. (J.S., D.P.Z.); the Division of Infectious Diseases, St. Paul's Hospital and University of British Columbia, Vancouver (P.P.); the Division of Infectious Diseases, Toronto Hospital and University of Toronto, Toronto (I.S., S.L.W.); the Division of Infectious Diseases, St. Michael's Hospital and University of Toronto, Toronto (I.W.F.); the Division of Infectious Diseases, University of Calgary, Calgary, Alta. (M.J.G.); the Division of Infectious Diseases, Sunnybrook Health Science Centre and University of Toronto, Toronto (A.R.R.); the Division of Infectious Diseases, Montreal Chest Institute and McGill University, Montreal (R.G.L.); the Division of Infectious Diseases, Wellesley Hospital and University of Toronto, Toronto (M.M.F.); and the Division of Immunology, Montreal General Hospital and McGill University, Montreal (C.M.T.).

Address reprint requests to Dr. Shafran at the Division of Infectious Diseases, Department of Medicine, University of Alberta, 2E4.11 Walter C. Mackenzie Health Sciences Centre, 8440–112 St., Edmonton, AB T6G 2B7, Canada.

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