A randomized evaluation of ethambutol for prevention of relapse and drug resistance during treatment of Mycobacterium avium complex bacteremia with clarithromycin-based combination therapy. California Collaborative Treatment Group.
Patients with AIDS and Mycobacterium avium complex (MAC) bacteremia are at high risk for relapse and emergence of resistant isolates during monotherapy with clarithromycin. Ninety-five AIDS patients with MAC bacteremia received clarithromycin plus clofazimine, with or without ethambutol, in a prospective, multicenter, randomized open-label trial. Of 80 patients with positive baseline cultures, sterilization or a 2 log10 reduction in colony-forming units of MAC in two consecutive blood cultures occurred in 69% of both groups. There were nine relapses in the two-drug arm and three in the three-drug arm. Kaplan-Meier estimates of risk of relapse at 36 weeks were 68% and 12%, respectively (P = .004). All relapse isolates were resistant to clarithromycin. Median time to clarithromycin resistance was 16 weeks with two drugs and 40 weeks with three drugs (P = .004). Ethambutol reduced relapses and emergence of clarithromycin resistance and should be considered an essential component of clarithromycin-based therapies for MAC bacteremia.
Dubé
M P
MP
University of Southern California School of Medicine, Los Angeles, USA.
Sattler
F R
FR
Torriani
F J
FJ
See
D
D
Havlir
D V
DV
Kemper
C A
CA
Dezfuli
M G
MG
Bozzette
S A
SA
Bartok
A E
AE
Leedom
J M
JM
Tilles
J G
JG
McCutchan
J A
JA
D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D000995:Antitubercular Agents / Q000008:administration & dosage*; D016470:Bacteremia / Q000188:drug therapy*; D017291:Clarithromycin / Q000008:administration & dosage* / Q000009:adverse effects; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination; D004977:Ethambutol / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy*; D011446:Prospective Studies; D012008:Recurrence
D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents; D004977:Ethambutol; D017291:Clarithromycin