Mycobacterium Avium Intracellulare Complex (MAC) Study
Mycobacterium Avium Intracellulare Complex (MAC) Study
This study is short course (3 month) multiple drug antibiotic therapy. The purpose of this
 research study is to evaluate the clinical and radiology response to assess whether drug
 resistance develops and assess quality of life measures with MAC disease.
The goal of this pilot study is to assess the safety and efficacy of short course (3 months)
 multiple drug antimicrobial therapy in adults with MAC pulmonary disease associated with
 multifocal bronchiectasis and multiple small nodules. We propose to evaluate the clinical and
 radiographic response, assess whether macrolide (either Clarithromycin or Azithromycin)
 resistance develops, and assess quality of life measures.

 No evidence of efficacy is required to proceed to longer term studies; however, we will need
 to confirm lack of development of macrolide resistance in this pilot study before proceeding
 to any additional studies to evaluate the efficacy of short course MAC treatment.

 Once we have demonstrated the feasibility of short course therapy and confirm that resistance
 to macrolides does not develop, we hope to apply for external funding to support a longer
 term randomized controlled trial comparing "standard" MAC therapy (which usually consists of
 a period of eighteen to twenty-four months with at least three antimicrobials) to short
 course (three months) MAC antimicrobial treatment, alternating each year with nine months of
 non-MAC bronchial hygiene measures for two consecutive years. If a larger study confirms
 efficacy of this approach, we would then propose even larger multi-site studies to test the
 hypothesis that short course MAC therapy alternating every year with non-MAC bronchial
 hygiene therapy should be considered in all adult patients with MAC pulmonary disease
 associated with multifocal bronchiectasis and multiple small nodules throughout their lives.

 The longer term goal of this research is to develop an optimal treatment strategy for these
 patients (in whom MAC will likely persist indefinitely) that will result in not only a better
 quality of life, but less evidence of long term lung damage, less risk of drug-related
 morbidity, and be better tolerated by the patients compared to current treatment strategies.

 The specific aims of this pilot study are as follows:

 Primary Aim:

 1. Confirm that macrolide (either Clarithromycin or Azithromycin) resistance does not
 develop as a result of short course treatment.

 Secondary Aims:

 2. Assess for change in quality of life metrics (St. George Respiratory Questionnaire and
 SF 12) from baseline to the conclusion of the study period (six months). We expect to
 see improvement in quality of life measures as a result of this short course treatment
 trial.

 3. Assess for change in pulmonary function from baseline to the conclusion of the study
 period. We expect to see improvement particularly in the FEV1, FEV1/FVC, and diffusing
 capacity for carbon monoxide as a result of this short course treatment trial.

 4. Assess for change in high resolution computerized tomography (HRCT) of the chest,
 evidence of MAC pulmonary disease (multifocal bronchiectasis associated with multiple
 small nodules) from baseline to the conclusion of the study period. We do not anticipate
 being able to demonstrate improvement in the HRCT evidence of MAC lung disease during
 the short period of this trial since these changes usually occur quite slowly.
Inclusion Criteria:

 1. All patients must meet diagnostic criteria for nontuberculous mycobacterial pulmonary
 disease as per ATS/IDSA Official Statement (AJRCCM Vol 175 pp 367-416, 2007)

 2. Confirmation both by a chest radiologist and the investigators of multifocal
 bronchiectasis and multiple small nodules on HRCT scanning of the chest

 3. Repeatedly positive sputum cultures and/or bronchial washings for MAC (in accordance
 with microbiologic diagnostic criteria outline by the American Thoracic Society)

 4. MAC must be proven to be macrolide (either Clarithromycin or Azithromycin) sensitive
 at the onset of the study

 5. Age greater than 18

 6. No active treatment for MAC lung disease within the past two years

 7. Patients and their physicians must be willing to discontinue other non-MAC
 antimicrobials which may have been used as part of their pre-study bronchial hygiene
 program.

 Exclusion Criteria:

 1. History of Cystic Fibrosis or HIV disease

 2. Known allergy or intolerance to any of the proposed antibiotics

 3. Inability to return at three month intervals for testing over the six month study
 period

 4. Inability to complete quality of life questionnaires

 5. Pregnancy

 6. Presence of any abnormality on baseline ophthalmological examination which would
 preclude the use of ethambutol.

 7. Coexistence of non-tuberculous mycobacteria other than MAC