The Microbiological and Clinical Effects of Combined Therapy according to Guidelines on the Treatment of Pulmonary Mycobacterium avium Complex Disease in Japan – Including a Follow-Up Study

Background: The difficulty of treatment for pulmonary Mycobacterium avium complex (MAC) in Japan. Objectives: To investigate the clinical and microbiological effects of treatment according to the guidelines proposed by the American Thoracic Society and the Japanese Society for Tuberculosis and prospective follow-up studies after the completion of treatment of patients with pulmonary MAC disease. Methods: Analysis of the microbiological effects with regard to sputum conversion rate and the sputum relapsing rate and the clinical effects with regard to clinical symptoms and radiological findings for patients with pulmonary MAC disease treated with a regimen consisting of rifampicin, ethambutol, streptomycin, and clarithromycin over 24 months and follow-up over 12 months. Results: Sixty-five patients with pulmonary MAC disease were enrolled in this trial. In 39 patients, negative sputum conversion was observed within 6 months after the initiation of this regimen, 16 relapsed, and 20 experienced clinical worsening within 1 year after the completion of treatment. Although retreatment with the same regimen or a regimen including new quinolones was carried out for these patients, we could not achieve negative sputum conversion and/or clinical improvement. Conclusions: We believe that the dose of clarithromycin for pulmonary MAC disease may be increased and recommend surgery for patients with a localized lesion at early-stage MAC disease to prevent a high rate of relapse.

[1]  M. Sakatani [Nontuberculous mycobacteriosis (NTM) in Japan--epidemiologic and clinical study]. , 1994, Kekkaku : [Tuberculosis].

[2]  R. Wallace,,et al.  Reduced serum levels of clarithromycin in patients treated with multidrug regimens including rifampin or rifabutin for Mycobacterium avium-M. intracellulare infection. , 1995, The Journal of infectious diseases.

[3]  Eric R. Ziegel,et al.  Biostatistics: A Foundation for Analysis in the Health Sciences , 1988 .

[4]  R. Wallace,,et al.  Susceptibility testing of slowly growing mycobacteria by a microdilution MIC method with 7H9 broth , 1986, Journal of clinical microbiology.

[5]  E. Wolinsky Mycobacterium avium strains resistant to clarithromycin and azithromycin , 1994, Antimicrobial Agents and Chemotherapy.

[6]  A. Niimi,et al.  Effect of clarithromycin regimen for Mycobacterium avium complex pulmonary disease. , 1999, American journal of respiratory and critical care medicine.

[7]  C. Kunin Antimicrobial activity of rifabutin. , 1996, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[8]  R. Wallace,,et al.  Activities of clarithromycin against eight slowly growing species of nontuberculous mycobacteria, determined by using a broth microdilution MIC system , 1992, Antimicrobial Agents and Chemotherapy.

[9]  Wayne W. Daniel,et al.  Biostatistics: A Foundation for Analysis in the Health Sciences , 1974 .

[10]  R. Wallace,,et al.  Diagnosis and treatment of disease caused by nontuberculous mycobacteria. , 1990, The American review of respiratory disease.

[11]  R. Wallace,,et al.  Drug intolerance to high-dose clarithromycin among elderly patients. , 1993, Diagnostic microbiology and infectious disease.

[12]  S. Shafran,et al.  Uveitis and pseudojaundice during a regimen of clarithromycin, rifabutin, and ethambutol. MAC Study Group of the Canadian HIV Trials Network. , 1994, The New England journal of medicine.

[13]  R. Baughman Cytomegalovirus: the monster in the closet? , 1997, American journal of respiratory and critical care medicine.

[14]  R. Wallace,,et al.  Clarithromycin regimens for pulmonary Mycobacterium avium complex. The first 50 patients. , 1996, American journal of respiratory and critical care medicine.