Mycobacterium Avium Complex
Conditions
Brief summary
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
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.
Interventions
DRUGAzithromycin
Azithromycin 250 mg PO daily
Sponsors
Johns Hopkins University
National Institute of Allergy and Infectious Diseases (NIAID)
American College of Chest Physicians
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Mycobacterium Avium Colony Count in Sputum | Day 0 and Day 15 | 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 15. |
| Mean Change in Time to Positivity of Mycobacterium Avium Growth in the Mycobacterial Growth Indicator Tube (MGIT) | Day 0 and Day 15 | The time (hours) to positivity in MGIT of Mycobacterium avium will be compared between baseline and day 15. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Mycobacterium Avium Colony Count in Sputum | Day 0 and Day 8 | 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 8. |
| Mean Change in Time to Positivity of Mycobacterium Avium Growth in MGIT | Day 0 and Day 8 | The time (hours) to positivity in MGIT of Mycobacterium avium will be compared between baseline and day 8. |
| Estimation of Plasma Azithromycin Area-under-the-curve (AUC) Following Oral Dosing Azithromycin | Pre-dose, 2, 4 and 6 hours post-dose on day 15 (range: 11-19 days) | Area-under-the-curve (ug/mL\*hr) will be predicted from plasma azithromycin levels using population pharmacokinetic modeling methods. |
| Estimation of Maximum Plasma Concentration (Cmax) of Azithromycin | Pre-dose, 2, 4 and 6 hours post-dose on day 15 (range: 11-19 days) | Peak concentration (Cmax) will be predicted from plasma drug concentration in ug/mL following oral dosing of azithromycin. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORElisa H Ignatius, MD
Johns Hopkins University
Participant flow
Recruitment details
Participants were recruited from the Johns Hopkins Center for Nontuberculous Mycobacteria and Bronchiectasis at Bayview Medical Center, Johns Hopkins Health System. Written informed consent was required for study participation.
Pre-assignment details
Of 10 consented participants, 10 met inclusion criteria and were assigned treatment.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 71.5 years STANDARD_DEVIATION 5 |
| Baseline Colony Forming Unit | 2.66 log10 CFU/mL STANDARD_DEVIATION 1.48 |
| Baseline Time to Positivity | 129.3 hours |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Region of Enrollment United States | 10 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 10 |
| other Total, other adverse events | 1 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
None listed