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

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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
  • Publisher: Public Library of Science (PLoS)
  • Journal: PLoS ONE, volume 11, issue 11 (issn: 1932-6203, eissn: 1932-6203)
  • Related identifiers: doi: 10.1371/journal.pone.0166220, pmc: PMC5115705
  • Subject: Microbial Control | Microbial Pathogens | Pseudomonas Aeruginosa | Molds (Fungi) | Pseudomonas | Research Article | Bacteria | Anatomy | Throat | Pathology and Laboratory Medicine | Sputum | Antimicrobials | Pathogens | Staphylococcus | Pharmacology | Aspergillus | Fungal Pathogens | Staphylococcus Aureus | Biology and Life Sciences | Stenotrophomonas Maltophilia | Drugs | Microbiology | Physiology | Medicine | Bacterial Pathogens | Body Fluids | Neck | Mucus | Medical Microbiology | Q | R | Fungi | Virology | Science | Organisms | Aspergillus Fumigatus | Medicine and Health Sciences | Co-Infections | Mycology | Antibiotics

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. Trial Registration ClinicalTrials.gov NCT00669760
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