Therapeutic effects of various initial combinations of chemotherapy including clarithromycin against Mycobacterium avium complex pulmonary disease

Chest. 2009 Dec;136(6):1569-1575. doi: 10.1378/chest.08-2567. Epub 2009 Jun 19.

Abstract

Background: The objective of this study was to find an optimal initial combination chemotherapy that includes clarithromycin (CAM) for treatment-naive patients with Mycobacterium avium complex (MAC) pulmonary disease, as assessed by microbiological conversion using a Mycobacterium growth indicator tube (MGIT).

Methods: Thirty-four patients with treatment-naive MAC pulmonary disease (determined using 1997 American Thoracic Society criteria) were evaluated retrospectively. They demonstrated a nodular and bronchiectatic pattern without cavity on high-resolution CT (HRCT) scans. The following three regimens were administered: regimen A (n = 9) consisted of CAM (400 mg/d), ethambutol (EB) [750 mg/d], and rifampicin (RFP) [450 mg/d]; regimen B (n = 12) consisted of CAM (800 mg/d), EB (750 mg/d), and RFP (450 mg/d); and regimen C (n = 13) consisted of CAM (800 mg/d), EB (1,000 mg/d), and RFP (600 mg/d) during the first 2 months followed by a reduction of the dosage of EB from 1,000 to 750 mg/d. Gender, age, BMI, and HRCT scan finding scores were not significantly different among the three groups. Chemotherapy was continued for 18 months. Sputum culture was periodically assessed by MGIT.

Results: Culture conversion at 18 months in regimen A (55.6%), which included a daily dosage of 400 mg of CAM (9.5 mg/kg), was significantly inferior to that in regimen B (91.7%), which included daily 800 mg of CAM (17.6 mg/kg; p < 0.05), but regimen B and C (92.3%) showed no between-group difference after > 18 months of chemotherapy.

Conclusions: The higher dose of CAM allowed for better culture conversion. Daily combination chemotherapy that includes CAM (800 mg) seems appropriate as an initial treatment against treatment-naive patients with nodular and bronchiectatic MAC pulmonary disease.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bronchiectasis / diagnostic imaging
  • Clarithromycin / administration & dosage
  • Dose-Response Relationship, Drug
  • Ethambutol / administration & dosage
  • Female
  • Humans
  • Lung / diagnostic imaging
  • Lung / microbiology
  • Lung Diseases / diagnostic imaging
  • Lung Diseases / drug therapy*
  • Lung Diseases / microbiology*
  • Male
  • Middle Aged
  • Mycobacterium avium Complex*
  • Mycobacterium avium-intracellulare Infection / drug therapy*
  • Retrospective Studies
  • Rifampin / administration & dosage
  • Tomography, X-Ray Computed
  • Treatment Outcome

Substances

  • Ethambutol
  • Clarithromycin
  • Rifampin