Early Methicillin-resistant Staphylococcus Aureus (MRSA) Therapy in Cystic Fibrosis (CF)
Condition: Cystic Fibrosis; Methicillin-resistant Staphylococcus Aureus
MeSH terms: Staphylococcal Infections; Cystic Fibrosis; Fibrosis
Intervention: Rifampin; Trimethoprim/Sulfamethoxazole; Minocycline; Mupirocin; chlorhexidine gluconate oral rinse; 2% Chlorhexidine solution wipes; Environmental Decontamination
Intervention description: Adult Dose: 300mg twice daily for 14 days. Pediatric Dose: <40kg : 15mg/kg daily for 14 days divided every 12 hours.; Adult Dose: 320/1600 orally twice daily for 14 days. Pediatric Dose: <40 kg : 8mg/kg trimethoprim / 40 mg/kg sulfamethoxazole twice a day for 14 days.; only subjects greater or equal to 8 years of age, who are not able to tolerate TMP/SMX or whose screening MRSA is resistant to TMP/SMX should be prescribed minocycline.
Adult dose: 100 mg orally twice daily for 14 days Pediatric dose: < 50 kg : 2mg/kg orally twice daily for 14 days not to exceed 200mg per day.; 1 gram 2% nasal ointment generously applied to each nostril using a cotton swab twice daily for 14 days.; for subjects able to swish without swallowing. 0.12% chlorhexidine gluconate oral rinse twice daily for 14 days.; whole body wash solution wipes once daily for first 5 days.; wipe down high touch surfaces and medical equipment with surface disinfecting wipes daily for the first 21 days.
wash all linens and towels in hot water once weekly for three weeks.
Intervention MeSH terms: Chlorhexidine; Chlorhexidine gluconate; Minocycline; Rifampin; Trimethoprim; Sulfamethoxazole; Mupirocin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Investigator)
Masking description: Although this is an open-label study, the PIs and operational study team will remain blinded to the study arm assignments of the aggregate study population and will not view aggregate study results by study arm until after database lock.
Enrollment: 47.0
Sex: All
Minimum age: 4 Years
Maximum age: 45 Years
Healthy volunteers: No
Keywords: MRSA; Cystic Fibrosis; Early Infection; Treatment

Summary:

      Purpose: There has been a recent, rapid increase in prevalence of Methicillin-resistant
      Staphylococcus aureus (MRSA) among patients with Cystic Fibrosis (22% across US CF centers in
      2009). Some epidemiologic studies suggest possible worse outcomes, a recent analyses showing
      this with chronic but not intermittent MRSA. Given the chronic difficult to treat lung
      infections in CF it is unclear how the onset of MRSA should be approached. This randomized,
      controlled, interventional study seeks to determine if an early eradication protocol is
      effective for eradication of MRSA and will provide an opportunity to obtain data regarding
      early clinical impact of new isolation of MRSA.

      Participants: Cystic fibrosis patients with new isolation of MRSA from their respiratory
      culture on a routine clinic visit.

      Procedures (methods): Randomized, open-label, multi-center study comparing use of an
      eradication protocol to an observational group who receives the current standard of care i.e.
      treatment for MRSA only with pulmonary exacerbations.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female ≥ 4 and ≤ 45 years of age at the Screening Visit.

          2. Documentation of a CF diagnosis as evidenced by one or more clinical features
             consistent with the CF phenotype and one or more of the following criteria:

               -  sweat chloride ≥ 60 mEq/liter by quantitative pilocarpine iontophoresis test
                  (QPIT)

               -  two well-characterized mutations in the cystic fibrosis transmembrane conductive
                  regulator (CFTR) gene

               -  Abnormal nasal potential difference (change in NPD in response to a low chloride
                  solution and isoproteronol of less than -5 mV)

          3. First OR early repeat MRSA colonization defined as:

               -  First MRSA colonization: first documented isolation of MRSA from respiratory
                  tract occurred ≤ 6 months prior to screening

               -  OR Early repeat MRSA colonization:

             MRSA was previously isolated from the respiratory tract (≤ 2 times), but this was
             followed by at least 1 year of documented negative cultures for MRSA as noted below:

             -- At least 2 cultures performed at least 3 months apart to document 1 year of culture
             negativity. Each of these cultures should be documented to have been collected at
             least 1 week after end of any antibiotic prescription with MRSA activity.

             Patient again recently positive for MRSA from the respiratory tract (within 6 months
             prior to screening)

          4. Clinically stable with no significant changes in health status within the 14 days
             prior to screening

          5. 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

        A repeat culture from the respiratory tract is obtained at screening but does not have to
        be positive to be able to enter the study.

        Exclusion Criteria:

          1. Received antibiotics with activity against MRSA within 28 days prior to screening (see
             study manual for list of antibiotics)

          2. Use of an investigational agent within 28 days prior to screening

          3. For subjects ≥ 6 years of age: FEV1 at screening < 30% of predicted for age based on
             the Wang (males < 18 years, females < 16 years) or Hankinson (males ≥ 18 years,
             females ≥ 16 years) standardized equations

          4. MRSA from the screening culture resistant to rifampin OR resistant to both TMP/SMX and
             minocycline

          5. History of intolerance to oral rifampin, or topical chlorhexidine or mupirocin

          6. History of intolerance to both TMP/SMX and minocycline

          7. < 8 years of age and either allergic or intolerant to TMP/SMX or screening MRSA
             resistant to TMP/SMX

          8. ≥ 8 years of age and allergic or intolerant to TMP/SMX and screening MRSA resistant to
             minocycline

          9. ≥ 8 years of age and allergic or intolerant to minocycline and screening MRSA
             resistant to TMP/SMX

         10. For females of child bearing potential: pregnant, breastfeeding, or unwilling to use
             barrier contraception through Day 15 of the study

         11. Abnormal renal function at Screening, defined as estimated creatinine clearance <50
             mL/min using the Cockcroft-Gault equation

         12. Abnormal liver function at the time of screening, defined as ≥2x upper limit of normal
             (ULN), of serum aspartate transaminase (AST) or serum alanine transaminase (ALT)

         13. History of solid organ or hematological transplantation

         14. Presence of a condition or abnormality that in the opinion of the Investigator would
             compromise the safety of the patient or the quality of the data.