title: Efficacy of clarithromycin and ethambutol for Mycobacterium avium complex pulmonary disease. A preliminary study.
abstract: BACKGROUND
  Patients with Mycobacterium avium complex pulmonary disease are frequently administered a combination of clarithromycin, ethambutol, and rifampicin. However, rifampicin is known to reduce the serum levels of clarithromycin. It remains unclear whether a reduction in clarithromycin serum levels influences the clinical outcome of the Mycobacterium avium complex pulmonary disease treatment regimen.
  
  
  OBJECTIVE
  To compare a three-drug regimen (clarithromycin, ethambutol, and rifampicin) to a two-drug regimen (clarithromycin and ethambutol) for the treatment of Mycobacterium avium lung disease.
  
  
  METHODS
  In a preliminary open-label study, we randomly assigned newly diagnosed, but as-yet untreated, patients with disease caused by Mycobacterium avium complex without HIV infection to either the three-drug or the two-drug regimen for 12 months. The primary endpoint was the conversion of sputum cultures to negative after 12 months of treatment. Patient data were analyzed using the intention-to-treat method.
  
  
  RESULTS
  Of 119 eligible patients, 59 were assigned to the three-drug regimen and 60 to the two-drug regimen. The rate of sputum culture conversion was 40.6% with the three-drug regimen and 55.0% with the two-drug regimen (difference, -14.4% [95% confidence interval, -32.1 to 3.4]). The incidence of adverse events leading to the discontinuation of treatment was 37.2 and 26.6% for the three-drug and the two-drug regimens, respectively.
  
  
  CONCLUSIONS
  This preliminary study suggests that treatment with clarithromycin and ethambutol is not inferior to treatment with clarithromycin, ethambutol, and rifampicin for Mycobacterium avium complex lung disease. Our findings justify a larger clinical trial to compare long-term clinical outcomes for the two treatment regimens. Clinical trial registered with http://www.umin.ac.jp/english/ (UMIN000002819).
authors.affiliation: 1 Department of Respiratory Medicine, Tenryu Hospital, National Hospital Organization, Hamamatsu, Japan; and.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Miwa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Shirai
authors.forename: Mikio
authors.initials: M
authors.lastname: Toyoshima
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Shirai
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Yasuda
authors.forename: Koshi
authors.initials: K
authors.lastname: Yokomura
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamada
authors.forename: Masafumi
authors.initials: M
authors.lastname: Masuda
authors.forename: Naoki
authors.initials: N
authors.lastname: Inui
authors.forename: Kingo
authors.initials: K
authors.lastname: Chida
authors.forename: Takafumi
authors.initials: T
authors.lastname: Suda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hayakawa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000904:Antibiotics, Antitubercular / Q000627:therapeutic use; D000995:Antitubercular Agents / Q000627:therapeutic use*; D017291:Clarithromycin / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004977:Ethambutol / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015269:Mycobacterium avium Complex / Q000302:isolation & purification; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy*; D012293:Rifampin / Q000627:therapeutic use; D013183:Sputum / Q000382:microbiology; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy*
chemical_list: D000900:Anti-Bacterial Agents; D000904:Antibiotics, Antitubercular; D000995:Antitubercular Agents; D004977:Ethambutol; D017291:Clarithromycin; D012293:Rifampin