Improving Treatment of Nontuberculous Mycobacterial Infection in Cystic Fibrosis

CF Subject Inclusion Criteria:

• CF diagnosis defined as a sweat chloride >60mEq/L and/or the presence of two disease-causing CFTR mutations.
• Ages 16 years and above.
• Pancreatic insufficient status defined as previous fecal pancreatic elastase <100mcg/g stool and/or having 2 disease-causing CFTR mutations known to be associated with pancreatic insufficiency, and taking supplemental pancreatic enzymes between 1000-2500 lipase units/kg/meal.
• No positive NTM cultures in the last 2 years.
• Pulmonary function: Most recent FEV1 > 40% predicted.
• Willing to participate in and comply with the study procedures, and willingness of a parent or legally authorized representative to provide written informed consent for those subjects less than 18 years of age.

Healthy Control Inclusion Criteria:

• Ages 18 years and above.
• BMI below 30 to best match CF body type.
• Willing to participate in and comply with the study procedures, and willingness of a parent or legally authorized representative to provide written informed consent for those subjects less than 18 years of age.

CF Subject Exclusion Criteria:

• Allergy or intolerance to rifampin, ethambutol, or azithromycin.
• Hepatic insufficiency defined as having an AST or ALT greater than three times the upper limit of normal at the screening appointment.
• Previous surgical bowel resection.
• Previous lung transplant.
• Use of medications known to interact with the antimycobacterial drug levels; of note, the most common interactions in CF patients are the use of itraconazole, voriconazole, and ivacaftor. We will have subjects hold H2 blockers and proton pump inhibitors for 3 days prior to each PK study day.
• Inability to hold azithromycin: Subjects will not be excluded if they are on chronic azithromycin for immunomodulatory purposes; however, we will ask that the subjects hold the azithromycin starting at the screening visit, through a 2 week wash-out period prior to Visit 2, and remain off through the end of Visit 3 (about 4 weeks total).
• Acute exacerbations: exclusion if any addition of oral, IV, or inhaled antibiotics, or an acute gastrointestinal illness with vomiting or diarrhea in the 2 weeks prior to each visit. No exclusion for previously prescribed alternating chronic inhaled or oral antibiotics.
• We will also exclude pregnant women (urine pregnancy test will be performed for females on the day of each PK study) and decisionally challenged subjects.

Healthy Control Exclusion Criteria:

• Allergy or intolerance to rifampin, ethambutol, or azithromycin.
• Hepatic insufficiency defined as having an AST or ALT greater than three times the upper limit of normal at the screening appointment.
• Previous chronic GI disease or surgical bowel resection.
• Use of medications known to interact with the antimycobacterial drug levels. We will have subjects hold H2 blockers and proton pump inhibitors for 3 days prior to the PK study day.
• Acute illness: exclusion if respiratory illness requiring antibiotics or gastrointestinal illness with vomiting or diarrhea in the 2 weeks prior to the PK visit.
• We will also exclude pregnant women (urine pregnancy test will be performed on the day of PK study) and decisionally challenged subjects.