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Dissection of Staphylococcus Aureus Infection From Colonization in Cystic Fibrosis Patients

Completed
Conditions
Cystic Fibrosis
Interventions
Other: non-interventional study
Registration Number
NCT00669760
Lead Sponsor
University Hospital Muenster
Brief Summary

Staphylococcus aureus is not only one of the first pathogens infecting the airways of cystic fibrosis (CF) patients, but also a highly prevalent microorganism (\>60% of all CF patients; European and American CF registries; (4,25), which often persists for several years in the respiratory tract of CF patients.

The purpose of this study is to dissect infection by S. aureus from colonization. Therefore, the following non-interventional prospective, longitudinal multicenter study will be conducted to develop the following hypothesis:

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

Primary endpoint: bacterial load of sputum cultures

Secondary endpoints:

* nasal carriage

* molecular analysis of S. aureus (Monoclonal/polyclonal)

* serum: S. aureus-specific antibodies, S100A12, IL-8, TNF-alpha

* sputum: S100A12, IL-8, myeloperoxidase

* S. aureus therapy regimens

* lung function tests: FEV1, deltaFVC , deltaMEF25

* BMI development

Inclusion criteria: S. aureus cultures for more than 6 months within the last year, children (\>6 years) and patients, who are able to perform lung function tests Exclusion criteria: P. aeruginosa and/or B. cepacia cultures from the specimens for more than 6 months within the last year before recruitment or during the study period In addition to microbiological investigations and clinical laboratory tests, the actual clinical situation will be evaluated and reported during the study period. The results of this observational study will be used to carefully plan a clinical interventional study. Furthermore, with the results it might be possible to characterize a subpopulation of patients, which is at greater risk for S. aureus infections.

Detailed Description

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

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
195
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

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Observationnon-interventional studyCF-patients with persistent culture of Staphylococcus aureus in their respiratory specimens
Primary Outcome Measures
NameTimeMethod
bacterial load of sputum cultures [high (>/= 1000000CFU/ml); low (<1000000CFU/ml)]2 years
Secondary Outcome Measures
NameTimeMethod
antibody titres against S. aureus specific antigens; S100A12, IL-8, TNF-alpha, CRP2 years

Trial Locations

Locations (17)

Medizinische Universität Innsbruck

🇦🇹

Innsbruck, Austria

Clemenshospital

🇩🇪

Muenster, Germany

Charite Berlin Campus Benjamin Franklin

🇩🇪

Berlin, Germany

Dres Heuer-Runge-Sextro

🇩🇪

Hamburg, Germany

Clinic for Children and Adolescents Ruhr University Bochum St Josef Hospital

🇩🇪

Bochum, Germany

Universitätsklinikum Carl Gustav Carus

🇩🇪

Dresden, Germany

Ruhrlandklinik Essen-Heidhausen

🇩🇪

Essen, Germany

Medical School Hannover

🇩🇪

Hannover, Germany

University Clinics Jena

🇩🇪

Jena, Germany

Children's Hospital Osnabrueck

🇩🇪

Osnabrueck, Germany

University Clinics Tuebingen

🇩🇪

Tuebingen, Germany

Heinrich-Heine University Duesseldorf

🇩🇪

Duesseldorf, Germany

Universitätsklinikum Halle

🇩🇪

Halle, Germany

University Clinics Essen

🇩🇪

Essen, Germany

Children's Hospital Park Schoenfeld

🇩🇪

Kassel, Germany

Universitätsklinikum Leipzig

🇩🇪

Leipzig, Germany

University Clinics Muenster

🇩🇪

Muenster, Germany

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