title: 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.
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.
authors.affiliation: Department of Medicine, University of Alberta, Edmonton, Canada.
authors.forename: S D
authors.initials: SD
authors.lastname: Shafran
authors.forename: J
authors.initials: J
authors.lastname: Singer
authors.forename: D P
authors.initials: DP
authors.lastname: Zarowny
authors.forename: P
authors.initials: P
authors.lastname: Phillips
authors.forename: I
authors.initials: I
authors.lastname: Salit
authors.forename: S L
authors.initials: SL
authors.lastname: Walmsley
authors.forename: I W
authors.initials: IW
authors.lastname: Fong
authors.forename: M J
authors.initials: MJ
authors.lastname: Gill
authors.forename: A R
authors.initials: AR
authors.lastname: Rachlis
authors.forename: R G
authors.initials: RG
authors.lastname: Lalonde
authors.forename: M M
authors.initials: MM
authors.lastname: Fanning
authors.forename: C M
authors.initials: CM
authors.lastname: Tsoukas
mesh_terms: D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D000328:Adult; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000995:Antitubercular Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D002939:Ciprofloxacin / Q000627:therapeutic use; D017291:Clarithromycin / Q000627:therapeutic use; D002991:Clofazimine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004977:Ethambutol / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D015269:Mycobacterium avium Complex / Q000302:isolation & purification; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D017828:Rifabutin / Q000009:adverse effects / Q000627:therapeutic use; D012293:Rifampin / Q000627:therapeutic use; D016019:Survival Analysis; D016896:Treatment Outcome; D014605:Uveitis / Q000139:chemically induced
chemical_list: D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents; D017828:Rifabutin; D002939:Ciprofloxacin; D004977:Ethambutol; D002991:Clofazimine; D017291:Clarithromycin; D012293:Rifampin