PLoS ONE (Jan 2016)

Factors Associated with Worse Lung Function in Cystic Fibrosis Patients with Persistent Staphylococcus aureus.

  • Sibylle Junge,
  • Dennis Görlich,
  • Martijn den Reijer,
  • Bärbel Wiedemann,
  • Burkhard Tümmler,
  • Helmut Ellemunter,
  • Angelika Dübbers,
  • Peter Küster,
  • Manfred Ballmann,
  • Cordula Koerner-Rettberg,
  • Jörg Große-Onnebrink,
  • Eberhardt Heuer,
  • Wolfgang Sextro,
  • Jochen G Mainz,
  • Jutta Hammermann,
  • Joachim Riethmüller,
  • Ute Graepler-Mainka,
  • Doris Staab,
  • Bettina Wollschläger,
  • Rüdiger Szczepanski,
  • Antje Schuster,
  • Friedrich-Karl Tegtmeyer,
  • Sivagurunathan Sutharsan,
  • Alexandra Wald,
  • Jerzy-Roch Nofer,
  • Willem van Wamel,
  • Karsten Becker,
  • Georg Peters,
  • Barbara C Kahl

DOI
https://doi.org/10.1371/journal.pone.0166220
Journal volume & issue
Vol. 11, no. 11
p. e0166220

Abstract

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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.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.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).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.ClinicalTrials.gov NCT00669760.