Dissection of Staphylococcus Aureus Infection From Colonization in Cystic Fibrosis Patients

Protocol synopsis Title: Dissection of Staphylococcus aureus infection from colonization in cystic fibrosis patients. A non-interventional prospective, 2-year longitudinal multicenter study

Study objectives: The aim of the study is to dissect S. aureus infection from colonization of the pathogen in airway secretions of CF patients during a 2 year period by means of a non-interventional, prospective, longitudinal multicenter study.

The following hypothesis will be developed:

CF patients with high bacterial loads are more likely to be infected by S. aureus than patients with low bacterial loads.

Definition of infection:

• change in volume, colour or consistency of sputum (exacerbation)
• increased cough
• malaise, fatigue or lethargy
• body temperature more than 38°C
• new or increased hemoptysis
• anorexia or weight loss
• sinus pain or tenderness
• change in sinus discharge
• change in chest sounds
• ten percent decrease in pulmonary function from a previous recorded value (FEV1, MEF25)
• radiographic changes indicative of pulmonary infection

Primary endpoint: bacterial load of sputum cultures [high (>/= 106CFU/ml); low (<106CFU/ml)]

Secondary endpoints are:

• assessment of nasal S. aureus carriage
• serum samples: antibody titres against S. aureus specific antigens; S100A12, IL-8,TNF-alpha, CRP
• molecular analysis of S. aureus colonization/infection (monoclonal or heteroclonal)
• sputa analysis: activity of S100A12, IL-8 and myeloperoxidase
• antibiotic treatment regimens against S. aureus
• body mass index
• lung function tests: FEV1, deltaFVC, deltaMEF25

Extensive microbiological investigations will be performed when the patients are seen at their regular visits in the outpatient clinics or if exacerbations occur. During the study period of 2 years, at least 8 visits to the outpatient clinic should be recorded. The following clinical parameters will be documented:

• lung function
• body mass index (weight/height)
• antibiotic treatment Diagnosis: CF and positive S. aureus cultures for more than 6 months within the last year Localisation of the study: multicenter study in Germany Number of centers: Seven centres agreed already to participate in the study. More centers have been and will be contacted.

Design: non-interventional prospective, longitudinal multicenter study Planned number of patients/volunteers: 228 Inclusion criteria: positive S. aureus cultures for more than 6 months within the last year; children (>6 years) and patients with CF, who are able to perform lung function tests Exclusion criteria: Pseudomonas aeruginosa and/or Burkholderia cepacia colonization or infection for more than 6 months within the last year before recruitment; patients who have not been colonized with these pathogens before but acquire them within the study period and are colonized/infected for more than 6 months during the observation period

Inclusion criteria

• positive S. aureus cultures for more than 6 months within the last year; children (>6 years) and patients with CF, who are able to perform lung function tests

Exclusion criteria

• Pseudomonas aeruginosa and/or Burkholderia cepacia colonization or infection for more than 6 months within the last year before recruitment; patients who have not been colonized with these pathogens before but acquire them within the study period and are colonized/infected for more than 6 months during the observation period