Population structure of <i>Streptococcus agalactiae</i>: Depicted are the three major recognized burst groups of <i>S. agalactiae</i>.

<p>Sequence types that vary by one allele in their MLST profiles (single locus variants) are arranged in circles around the primary founder sequence type. The population structure diagram was created based on the <i>S. agalactiae</i> MLST database as found under: <a href="http://eburst.mlst.net" target="_blank">http://eburst.mlst.net</a>. Sequence types present in our collection of colonizing strains are depicted as closed circles, sequence types found in the <i>S. agalactiae</i> strains form CF patients are shown as open squares. The major clonal complexes (CC) are indicated in the picture.</p

Clinical characteristics of <i>S. agalactiae</i> (GBS) positive cystic fibrosis patients.

<p>Clinical characteristics of <i>S. agalactiae</i> (GBS) positive cystic fibrosis patients.</p

Figure 2

<p>A: Association between surface proteins and sequence types. For each sequence type found in either respiratory strains from CF patients or colonizing strains, the number of isolates and the surface proteins of these strains are shown. Genes coding for alpha C, Epsilon, Rib or Alp2/3 were detected in the vast majority of strains, only five isolates failed to generate a PCR product with the specific primers. B: Association between serotypes and sequence types. For each sequence type found in either respiratory strains from CF patients or colonizing strains, the number of isolates and the serotypes of these strains are shown.</p

Molecular characterization of 19 unique <i>S. agalactiae</i> strains from CF patients.

*<p>Nontypable.</p

Molecular characterization of 72 colonizing <i>S. agalactiae</i> strains from the urogenital and gastrointestinal tract.

<p>Molecular characterization of 72 colonizing <i>S. agalactiae</i> strains from the urogenital and gastrointestinal tract.</p

Patients with culture of <i>S</i>. <i>maltophilia</i> have worse lung function.

<p>Patients with <i>S</i>. <i>maltophilia</i> are indicated by red squares, patients without <i>S</i>. <i>maltophilia</i> by blue circles, fitted model prediction is coloured accordingly.</p

Factors Associated with Worse Lung Function in Cystic Fibrosis Patients with Persistent <i>Staphylococcus aureus</i>

<div><p>Background</p><p><i>Staphylococcus aureus</i> 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 <i>S</i>. <i>aureus</i> airway cultures. Our main hypothesis was that patients with high <i>S</i>. <i>aureus</i> density in their respiratory specimens would more likely experience worsening of their lung disease than patients with low bacterial loads.</p><p>Methods</p><p>Therefore, we conducted an observational prospective longitudinal multi-center study and assessed the association between lung function and <i>S</i>. <i>aureus</i> bacterial density in respiratory samples, co-infection with other CF-pathogens, nasal <i>S</i>. <i>aureus</i> carriage, clinical status, antibiotic therapy, IL-6- and IgG-levels against <i>S</i>. <i>aureus</i> virulence factors.</p><p>Results</p><p>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), <i>S</i>. <i>aureus</i> small-colony variants (SCVs, n = 84) and co-infection with <i>Stenotrophomonas maltophilia</i> (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), <i>S</i>. <i>aureus</i> density in sputa (p = 0.0016), SCVs (p = 0.0209), exacerbations (p = 0.0041) and co-infections with <i>S</i>. <i>maltophilia</i> (p = 0.0195) or <i>A</i>. <i>fumigatus</i> (p = 0.0496).</p><p>Conclusions</p><p>In CF-patients with chronic <i>S</i>. <i>aureus</i> cultures, independent risk factors for worse lung function are high bacterial density in throat cultures, exacerbations, elevated IL-6 levels, presence of <i>S</i>. <i>aureus</i> SCVs and co-infection with <i>S</i>. <i>maltophilia</i>.</p><p>Trial Registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT00669760" target="_blank">NCT00669760</a></p></div

Higher IL-6 is associated with lower FEV1% predicted.

<p>Scatterplot of baseline measurements (n = 88) of all patients with blood samples provided at the first visit. The fit line shows the results of a non-linear regression model. Dark shaded areas show 95% confidence band, lighter shaded area shows 95% prediction band.</p

Significant specific IgG levels against <i>S</i>. <i>aureus</i> antigens in CF patients compared to healthy controls.

<p>Significant specific IgG levels against <i>S</i>. <i>aureus</i> antigens in CF patients compared to healthy controls.</p

Patients with <i>S</i>. <i>aureus</i> nasal carriage have better lung function.

<p><i>S</i>. <i>aureus</i> nasal carriers are indicated by blue squares, non-nasal carriers by red circles, fitted model prediction is coloured accordingly.</p