A Study of Standard Drugs for Mycobacterium Avium Complex

Study Overview
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Brief Summary
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To assess the early bactericidal activity of Azithromycin 250mg by mouth daily over the first 14 days of treatment for Mycobacterium avium complex (MAC) lung disease.

Detailed Description
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This research is being done to better understand several important aspects of treatment of Mycobacterium avium complex (MAC) lung infections using an early bactericidal activity (EBA) study design. MAC is an environmental bacteria that can cause chronic lung infection. Early bactericidal activity is the amount of bacterial killing that occurs during the first few weeks of antibiotic treatment. By collecting information about the EBA of azithromycin for MAC, the investigators will quantify the efficacy of azithromycin against pulmonary MAC.

Official Title
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Early Bactericidal Activity of Standard Drugs Used to Treat Mycobacterium Avium Complex: a Pilot Study

Conditions
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Mycobacterium Avium Complex

Intervention / Treatment
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* Drug: Azithromycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years Isolation of M. avium intracellulare complex from a respiratory specimen in the preceding 6 months Fulfill American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) criteria for MAC lung disease Intention by the treating clinician to treat for MAC lung disease. Ability to produce a sputum sample of at least 10mL in a 16 hour period Signed informed consent by the subject Exclusion Criteria: Prior treatment for pulmonary MAC within the past 6 months Pregnancy HIV with a cluster of differentiation 4 (CD4) <350 History of solid organ or hematologic transplant Contraindication to azithromycin Has any other condition that, in the opinion of the PI, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 14 Day Azithromycin Monotherapy<br>For the first 14 days of therapy, participants will receive Azithromycin 250mg PO daily as monotherapy. Beyond day 14, all participants will receive guideline-based standard multi-drug therapy for Mycobacterium avium lung disease, as dictated by the physicians treating the participants. | Drug: Azithromycin<br>* Azithromycin 250 mg PO daily<br>* Other names: Zithromax;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mycobacterium avium colony count in sputum | The early bactericidal activity of azithromycin for Mycobacterium avium will be determined as the change in Mycobacterium avium colony count (log10 colony forming unit (CFU) per mL) in sputum between baseline and day 14. | Baseline and Day 14 | 
| Change in time to positivity of Mycobacterium avium growth in the Mycobacterial Growth Indicator Tube (MGIT) | The time (hours) to positivity in MGIT of Mycobacterium avium will be compared between Baseline and Day 14. | Baseline and Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mycobacterium avium colony count in sputum | The bactericidal activity of multidrug therapy for Mycobacterium avium will be determined as the change in Mycobacterium avium colony count (log10 CFU per mL) in sputum between baseline and day 7. | Baseline and Day 7 | 
| Change in Mycobacterium avium colony count in sputum | The bactericidal activity of multidrug therapy for Mycobacterium avium will be determined as the change in Mycobacterium avium colony count (log10 CFU per mL) in sputum between day 7 and day 14. | Day 7 to Day 14 | 
| Change in Mycobacterium avium colony count in sputum | The bactericidal activity of multidrug therapy for Mycobacterium avium will be determined as the change in Mycobacterium avium colony count (log10 CFU per mL) in sputum between baseline and 2 months. | Baseline and 2 Months | 
| Change in time to positivity of Mycobacterium avium growth in MGIT | The time (hours) to positivity in MGIT of Mycobacterium avium will be compared between baseline and day 7. | Baseline and Day 7 | 
| Change in time to positivity of Mycobacterium avium growth in MGIT | The time (hours) to positivity in MGIT of Mycobacterium avium will be compared between day 7 and day 14. | Day 7 and Day 14 | 
| Change in time to positivity of Mycobacterium avium growth in MGIT | The time (hours) to positivity in MGIT of Mycobacterium avium will be compared between baseline and 2 months. | Baseline and 2 Months | 
| Estimation of plasma azithromycin area-under-the-curve (AUC) following oral dosing azithromycin | Area-under-the-curve (ug/mL*hr) will be predicted from plasma azithromycin levels using population pharmacokinetic modeling methods. | Pre-dose, 2, 4 and 6 hours post-dose on day 15, and 2 and 6 hours post-dose on day 29 | 
| Estimation of maximum plasma concentration (Cmax) of azithromycin | Peak concentration (Cmax) will be predicted from plasma drug concentration in ug/mL following oral dosing of azithromycin. | Pre-dose, 2, 4 and 6 hours post-dose on day 15 | 
| Estimation of maximum plasma concentration (Cmax) of azithromycin | Peak concentration (Cmax) will be predicted from plasma drug concentration in ug/mL following oral dosing of azithromycin. | 2 and 6 hours post-dose on day 29 |