STaph Aureus Resistance-Treat Early and Repeat (STAR-TER)

Inclusion Criteria:

1. Male or female ≥ 2 and ≤ 45 years of age at the Screening Visit.

2. Documentation of a CF diagnosis as evidenced by one or more clinical featuresconsistent with the CF phenotype and one or more of the following criteria:

3. sweat chloride ≥ 60 milliequivalents/liter by quantitative pilocarpineiontophoresis test (QPIT)

4. two well-characterized mutations in the cystic fibrosis transmembraneconductive regulator (CFTR) gene

5. abnormal nasal potential difference(NPD) (change in NPD in response to a lowchloride solution and isoproteronol of less than -5 mV)

6. First OR early MRSA colonization defined as:

7. First MRSA colonization: first documented isolation of MRSA from respiratorytract occurred ≤ 6 months prior to screening

8. Early MRSA colonization: MRSA was previously isolated from the respiratorytract ≤ 2 times over the past 3.5 years, but this was followed by at least 1year of documented negative cultures for MRSA

9. MRSA is available to the central laboratory - either the incident MRSA isolate fromthe clinic visit or the subject is MRSA positive at the screening visit

10. Clinically stable with no significant changes in health status within the 14 daysprior to screening

11. Written informed consent (and assent when applicable) obtained from subject orsubject's legal representative and ability for subject to comply with therequirements of the study

Exclusion Criteria:

1. Received antibiotics with activity against MRSA within 28 days prior to screening

2. Use of an investigational agent within 28 days prior to screening

3. For subjects ≥ 6 years of age: FEV1 at screening < 25% of predicted for age based onthe Wang (males < 18 years, females < 16 years) or Hankinson (males ≥ 18 years,females ≥ 16 years) standardized equations

4. MRSA from the screening culture or the most recent clinical care visit within 6months prior to screening resistant to TMP/SMX

5. History of intolerance to topical chlorhexidine or mupirocin

6. History of intolerance to both TMP/SMX and minocycline

7. < 8 years of age and allergic or intolerant to TMP/SMX

8. ≥ 8 years of age and allergic or intolerant to TMP/SMX and MRSA isolate (fromscreening or clinical care visit)is resistant to minocycline

9. For females of child bearing potential: pregnant, breastfeeding, or unwilling to usebarrier contraception through Day 42 of the study

10. Subjects with history of abnormal renal function will need screening labs showingnormal function Abnormal renal function is defined as estimated creatinine clearance <50 mL/min using the:

11. Bedside Schwartz Equation for subjects <18 years of age, and

12. Levey Glomerular filtration rate (GFR) Equation for subjects ≥ 18 years of age.

13. Subjects with a history of abnormal liver function will need to have screening labsshowing normal transaminases. Liver dysfunction is defined as ≥3x upper limit ofnormal (ULN), of serum aspartate transaminase (AST) or serum alanine transaminase (ALT) or abnormal synthetic function

14. History of solid organ or hematological transplantation

15. Presence of a condition or abnormality that in the opinion of the Investigator wouldcompromise the safety of the patient or the quality of the data.