Factors associated with worse lung function in cystic fibrosis patients with persistent staphylococcus aureus

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Sibylle Junge - , Allergology and Neonatology (Author)
  • Dennis Görlich - , University of Münster (Author)
  • Martijn Den Reijer - , Erasmus University Rotterdam (Author)
  • Bärbel Wiedemann - , Institute for Medical Informatics and Biometry (Author)
  • Burkhard Tümmler - , Hannover Medical School (MHH) (Author)
  • Helmut Ellemunter - , Innsbruck Medical University (Author)
  • Angelika Dübbers - , University of Münster (Author)
  • Peter Küster - , Clemenshospital Münster (Author)
  • Manfred Ballmann - , Ruhr University Bochum (Author)
  • Cordula Koerner-Rettberg - , Ruhr University Bochum (Author)
  • Jörg Große-Onnebrink - , University of Duisburg-Essen (Author)
  • Eberhardt Heuer - , Paediatricians Kinderärztliche Ambulanz (Author)
  • Wolfgang Sextro - , Paediatricians Kinderärztliche Ambulanz (Author)
  • Jochen G. Mainz - , Friedrich Schiller University Jena (Author)
  • Jutta Hammermann - , Department of Paediatrics, University Hospital Carl Gustav Carus Dresden (Author)
  • Joachim Riethmüller - , University Hospital Tübingen (Author)
  • Ute M. Graepler-Mainka - , University Hospital Tübingen (Author)
  • Doris Staab - , Charité – Universitätsmedizin Berlin (Author)
  • Bettina Wollschläger - , Martin Luther University Hospital (Author)
  • Rüdiger Szczepanski - (Author)
  • Antje Schuster - , Heinrich Heine University Düsseldorf (Author)
  • Friedrich Karl Tegtmeyer - , Children's Hospital Park Schönfeld (Author)
  • Sivagurunathan Sutharsan - , University Hospital Essen (Author)
  • Alexandra Wald - , University Hospital Leipzig (Author)
  • Jerzy Roch Nofer - , University of Münster (Author)
  • Willem Van Wamel - , Erasmus University Rotterdam (Author)
  • Karsten Becker - , University of Münster (Author)
  • Georg Peters - , University of Münster (Author)
  • Barbara C. Kahl - , Allergology and Neonatology, University of Münster (Author)

Abstract

Background Staphylococcus aureus is an important pathogen in cystic fibrosis (CF). However, it is not clear which factors are associated with worse lung function in patients with persistent S. aureus airway cultures. Our main hypothesis was that patients with high S. aureus density in their respiratory specimens would more likely experience worsening of their lung disease than patients with low bacterial loads. Methods Therefore, we conducted an observational prospective longitudinal multi-center study and assessed the association between lung function and S. aureus bacterial density in respiratory samples, co-infection with other CF-pathogens, nasal S. aureus carriage, clinical status, antibiotic therapy, IL-6- and IgG-levels against S. aureus virulence factors. Results 195 patients from 17 centers were followed; each patient had an average of 7 visits. Data were analyzed using descriptive statistics and generalized linear mixed models. Our main hypothesis was only supported for patients providing throat specimens indicating that patients with higher density experienced a steeper lung function decline (p<0.001). Patients with exacerbations (n = 60), S. aureus small-colony variants (SCVs, n = 84) and co-infection with Stenotrophomonas maltophilia (n = 44) had worse lung function (p = 0.0068; p = 0.0011; p = 0.0103). Patients with SCVs were older (p = 0.0066) and more often treated with trimethoprim/sulfamethoxazole (p = 0.0078). IL-6 levels positively correlated with decreased lung function (p<0.001), S. aureus density in sputa (p = 0.0016), SCVs (p = 0.0209), exacerbations (p = 0.0041) and co-infections with S. maltophilia (p = 0.0195) or A. fumigatus (p = 0.0496). Conclusions In CF-patients with chronic S. aureus cultures, independent risk factors for worse lung function are high bacterial density in throat cultures, exacerbations, elevated IL-6 levels, presence of S. aureus SCVs and co-infection with S. maltophilia.

Details

Original languageEnglish
Article numbere0166220
JournalPloS one
Volume11
Issue number11
Publication statusPublished - Nov 2016
Peer-reviewedYes

External IDs

PubMed 27861524

Keywords

ASJC Scopus subject areas