Initial and Chronic Methicillin Resistant Staphylococcus Aureus (MRSA) Infection in Cystic Fibrosis (CF)
Condition: Methicillin-Resistant Staphylococcus Aureus; Cystic Fibrosis
MeSH terms: Staphylococcal Infections; Cystic Fibrosis; Fibrosis
Study type: Observational

Summary: 
      This study aims to examine features of MRSA that are associated with chronic MRSA infection
      and bacterial persistence despite IV antibiotic therapy. Subjects are asked to expectorate
      sputum and complete CF symptom diaries both at beginning and end of IV therapy.
    

Detailed description: 
      This is an observational, translational study examined bacterial morphology and function pre-
      vs. post antibiotic therapy in patients with CF who experience a pulmonary exacerbation that
      requires IV antibiotics.

      All clinical care is dictated by the treating physician(s).

      Inclusion criteria:

        1. Male or female with a confirmed diagnosis of CF (by sweat test and/or identification of
           2 CF disease causing mutations).

        2. Chronic infection with MRSA defined as having had MRSA positive respiratory cultures for
           > 1 year with > 50% of cultures being MRSA positive.

        3. Being able to expectorate sputum on a consistent basis, i.e. also at the end of IV
           therapy 3A: starting April 2017 people with CF who cannot expectorate sputum can also
           participate if they will do two orapharyngeal swab cultures.

        4. Having a pulmonary exacerbation defined for this protocol as the decision of the
           treating physician to start IV therapy in hospital or at home. Typically this occurs
           when there has been a >5% drop in FEV1 % predicted compared to the patient's baseline
           and increased respiratory symptoms.

             1. NOTE: Patients who had oral or inhaled antibiotics with or without MRSA activity
                but failed i.e. are changed to IV antibiotics are allowed to participate.

      Exclusion criteria:

        1. Presence / infection with B. cepacia genomovar III (B. cenocepacia)

        2. Subjects who have undergone lung or liver transplant in the past (NOTE: patients listed
           for transplant are eligible)

        3. Concomitant participation and/or use of an investigational drug within 30 days of this
           study. Concomitant observational studies are allowed with TRI-STAR

      Sputum collection:

      The subject will be asked to expectorate a sputum into a sterile specimen cup solely for this
      study. This may be a second sample after giving one for the clinical laboratory at start of
      therapy. The subject will be asked for a repeat sputum sample for the study at end of
      therapy.

      Time point definition: A) Start of therapy sample: up to 3 days prior and up to 36 hours
      after the first dose of anti-MRSA antibiotic. B) End of therapy: no earlier than 36 hours
      prior to the last dose and up to one week after completion.

      Collection of clinical information: Clinical information to be collected include:
      Demographics, age, CF genotype, anthropometrics; FEV1 FVC, FEF 25-75 in liter and % predicted
      per site specific reference values; all medications (routine and those started within 2 weeks
      and at time of admission/IV therapy).

      CF daily Symptom score: Subject will be asked to complete the CF Symptom diary for the first
      and last 3 days of IV therapy. For subjects admitted to the hospital this will be
      administered by the RC for those at home the RC will call / e-mail them as reminder or do it
      with them per phone.

      Spirometry at conclusion of therapy: Most patients have a follow-up clinic visit or are still
      in the hospital at time of completion of IV therapy and spirometry is part of routine
      clinical assessment. NOTE: Patients who would not have a clinic visit at end of therapy may
      be asked to return for spirometry and sputum sample solely for this study. If the subject
      agrees to this, reimbursement for travel will be allowed.

      Laboratory Assays:

      In vitro assays done on either banked isolates in Aim 1 or sputum samples / MRSA isolates
      from sputum include tests on bacterial fitness as growth under different conditions;
      antibiotic susceptibility assays; metabolic and virulence activity and genes, and mutator
      rates for sputum isolates. More details are provided in the grant application.
    

Intervention name(s): Intervention N/A. Observational study
Intervention type(s): Other
Intervention description(s): There are no interventions to the subjects other than collection of an expectorated sputum since this is an observational study; There are no study groups.See details per detailed study description.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients with a confirmed diagnosis of cystic fibrosis (CF), chronic MRSA who have a
        pulmonary exacerbation requiring IV therapy.
      
Biospecimen description: 
      -  Sputum

        -  Blood