title: Initial clarithromycin monotherapy for Mycobacterium avium-intracellulare complex lung disease.
abstract: Sputum conversion rates in Mycobacterium avium-intracellulare (MAI) complex lung disease have ranged from only 50 to 80% despite the use of three to five antituberculosis agents. We initiated a prospective, open, noncomparative trial of initial clarithromycin monotherapy at 500 mg twice a day for 4 months in HIV-negative patients with MAI lung disease. The primary study end point was microbiologic improvement. Of 30 patients enrolled, 20 completed therapy. This latter group was predominantly male (60%), smokers (70%), older than 45 yr of age (90%), infected with Mycobacterium intracellulare (70%) and with bilateral disease (85%). Of 19 patients with pretreatment minimum inhibitory concentrations (MIC) for clarithromycin < 16 micrograms/ml, 58% became sputum-negative, and 21% showed significant reductions in sputum positivity. Heavily positive sputum cultures (> 200 colonies) were reduced from 30 to 47 samples pretherapy (64%) to three of 54 (6%) post-therapy (p < 0.0001); 18 of 19 patients (95%) showed an improvement in sputum cultures, chest radiographs, or both. Only two patients (7%) discontinued the drug because of adverse events. Only three (16%) of 19 isolates developed clarithromycin resistance (MIC > 32 micrograms/ml). Clarithromycin-susceptible and -resistant MAI isolates from the same patient had identical DNA large-restriction fragment patterns. Clarithromycin is the first single agent to be shown efficacious in the treatment of MAI lung disease.
authors.affiliation: Department of Microbiology, University of Texas Health Center, Tyler 75710.
authors.forename: R J
authors.initials: RJ
authors.lastname: Wallace
authors.forename: B A
authors.initials: BA
authors.lastname: Brown
authors.forename: D E
authors.initials: DE
authors.lastname: Griffith
authors.forename: W M
authors.initials: WM
authors.lastname: Girard
authors.forename: D T
authors.initials: DT
authors.lastname: Murphy
authors.forename: G O
authors.initials: GO
authors.lastname: Onyi
authors.forename: V A
authors.initials: VA
authors.lastname: Steingrube
authors.forename: G H
authors.initials: GH
authors.lastname: Mazurek
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017291:Clarithromycin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D015269:Mycobacterium avium Complex / Q000187:drug effects / Q000302:isolation & purification; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy* / Q000382:microbiology; D011446:Prospective Studies; D013183:Sputum / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D017291:Clarithromycin