Persistent Methicillin Resistant Staphylococcus Aureus Eradication Protocol (PMEP)

Inclusion Criteria: 1. Male or female ≥ 12 years of age. 2. Confirmed diagnosis of CF based on the following criteria: positive sweat chloride \> 60 mEq/liter (by pilocarpine iontophoresis) and/or a genotype with two identifiable mutations consistent with CF or abnormal Nasal Potential Difference (NPD), and one or more clinical features consistent with the CF phenotype. 3. Written informed consent (and assent when applicable) obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study. 4. Two positive MRSA respiratory cultures in the last two years at least six months apart, plus a positive MRSA respiratory culture at Screening Visit and Run-in (Day -14) Visit. 5. At least 50% of respiratory cultures from the time of the first MRSA culture (in the last two years) have been positive for MRSA. 6. Forced Expiratory Volume (FEV)1 \> 40% of predicted normal for age, gender, and height at Screening, for subjects 18 years of age or older.. 7. FEV1\> 60% of predicted normal for age, gender, and height at Screening, for subjects 12--17 years of old. 8. Females of childbearing potential must agree to practice one highly effective method of birth control, including abstinence. Note: highly effective methods of birth control are those, alone or in combination, that result in a failure rate less than 1% per year when used consistently and correctly. Female patients who utilize hormonal contraceptives as a birth control method must have used the same method for at least 3 months before study dosing. If the patient is using a hormonal form of contraception, patients will be required to also use barrier contraceptives as rifampin can affect the reliability of hormone therapy. Barrier contraceptives such as male condom or diaphragm are acceptable if used in combination with spermicides Exclusion Criteria: 1. An acute upper or lower respiratory infection, pulmonary exacerbation, or change in routine therapy (including antibiotics) for pulmonary disease within 42 days of the Day 1 Visit (2 weeks prior to Screening visit). 2. Individuals on chronic continuous inhaled antibiotics without interruption who are not willing to substitute vancomycin or placebo for their scheduled inhaled antibiotic during days 0-28 of the study (every other month inhaled antibiotics are acceptable) 3. Use of oral or inhaled anti-MRSA drugs within two weeks of the Screening Visit. 4. History of intolerance to inhaled vancomycin or inhaled albuterol. 5. History of intolerance to rifampin or both TMP/SMX and doxycycline. 6. Resistance to rifampin or both TMP/SMX and doxycycline at Screening. 7. Resistance to vancomycin at Screening. 8. Abnormal renal function, defined as creatinine clearance \< 50 mL/min using the Cockcroft-Gault equation for adults or Schwartz equation in children, at Screening. 9. Abnormal liver function, defined as ≥ 3x upper limit of normal (ULN), of serum aspartate transaminase (AST) or serum alanine transaminase (ALT), or known cirrhosis. at the time of Screening. 10. Serum hematology or chemistry results which in the judgment of the investigator would interfere with completion of the study. 11. History of or listed for solid organ or hematological transplantation 12. History of sputum culture with non-tuberculous Mycobacteria in the last 6 months. 13. History of sputum culture with Burkholderia Cepacia in the last year. 14. Planned continuous use of soft contact lenses while taking rifampin and no access to glasses. 15. Current use of oral corticosteroids in doses exceeding the equivalent of 10 mg prednisone a day or 20 mg prednisone every other day 16. Administration of any investigational drug or device within 28 days of Screening or within 6 half-lives of the investigational drug (whichever is longer). 17. Patients on inhaled antibiotics must have been on the same regimen for the 4 months prior to screening 18. Female patients of childbearing potential who are pregnant or lactating, or plan on becoming pregnant 19. Any serious or active medical or psychiatric illness, which in the opinion of the investigator, would interfere with patient treatment, assessment, or adherence to the protocol.