Epidemiology and Treatment of Small-colony Variant Staphylococcus Aureus in Cystic Fibrosis

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 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 SCV-SA respiratory cultures in the last two years at least six months apart, plus a positive SCV-SA respiratory culture at Screening Visit and Run-in (Day -14) Visit. 5. FEV1 \>30% of predicted normal for age, gender, and height at Screening. 6. Weight \> 35 kg 7. 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 14 days of the screening visit. 2. Use of oral or inhaled anti-MRSA drugs within two weeks of the Screening Visit. 3. History of intolerance to rifampin or TMP/SMX, minocycline, and doxycycline. 4. Resistance to rifampin or TMP/SMX, minocycline and doxycycline at screening. 5. Abnormal renal function, defined as creatinine clearance \<50 mL/min using the Cockcroft-Gault equation for adults or Schwartz equation in children, at Screening. 6. 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. 7. Serum hematology or chemistry results which in the judgment of the investigator would interfere with completion of the study. 8. History of or listed for solid organ or hematological transplantation 9. History of sputum culture with non-tuberculous Mycobacteria in the last 6 months. 10. History of sputum culture with Burkholderia Cepacia in the last year. 11. Planned continuous use of soft contact lenses while taking rifampin and no access to glasses. 12. Taking voriconazole and unable to discontinue its use while enrolled in the study. 13. Administration of any investigational drug or device within 28 days of screening or within 6 half-lives of the investigational drug (whichever is longer) 14. Female patients of childbearing potential who are pregnant or lactating, or plan on becoming pregnant 15. 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. 16. Patients taking certain drugs will be excluded from the study: a. Drugs, which are contraindicated when rifampin is used (in addition to voriconazole): i. Antiretrovirals: fosamprenavir, atazanavir, lopinavir, saquinavir, nelfinavir, tipranavir, darunavir, rilpivirine,telaprevir, boceprevir, elvitegravir, maraviroc ii. Drugs used to increase systemic exposure of antiretrovirals: Cobicistat iii. Anthelmintic/Antimalarial agents: praziquantel, artemether iv. Antianginal agent: ranolazine v. Psychiatric medications: lurasidone b. Other drugs, not contraindicated, but listed as having major drug to drug interactions i. Antiretrovirals: ritonavir, indinavir, efavirenz, nevirapine, etavirine