Emergence of Respiratory Streptococcus agalactiae Isolates in Cystic Fibrosis Patients

Streptococcus agalactiae is a well-known pathogen for neonates and immunocompromized adults. Beyond the neonatal period, S. agalactiae is rarely found in the respiratory tract. During 2002–2008 we noticed S. agalactiae in respiratory secretions of 30/185 (16%) of cystic fibrosis (CF) patients. The median age of these patients was 3–6 years older than the median age CF patients not harboring S. agalactiae. To analyze, if the S. agalactiae isolates from CF patients were clonal, further characterization of the strains was achieved by capsular serotyping, surface protein determination and multilocus sequence typing (MLST). We found a variety of sequence types (ST) among the isolates, which did not substantially differ from the MLST patterns of colonizing strains from Germany. However serotype III, which is often seen in colonizing strains and invasive infections was rare among CF patients. The emergence of S. agalactiae in the respiratory tract of CF patients may represent the adaptation to a novel host environment, supported by the altered surfactant composition in older CF patients

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

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

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

Nasal Staphylococcus aureus Carriage Is Not a Risk Factor for Lower-Airway Infection in Young Cystic Fibrosis Patients▿

Staphylococcus aureus is one of the first pathogens which often persistently infect the airways of cystic fibrosis (CF) patients. Nasal S. aureus carriage is a risk factor for S. aureus infections in non-CF patients. Topical treatment strategies successfully eradicate nasal S. aureus carriage, thereby decreasing S. aureus infection. A prospective longitudinal multicenter study was conducted to assess whether nasal carriage represents a risk factor for S. aureus colonization of the oropharynx in young CF patients. Cross-sectional analysis revealed a significantly higher prevalence of S. aureus-positive nasal (28/80 [35%] versus 20/109 [18%]; P < 0.01) and oropharyngeal (35/80 [44%] versus 20/109 [18%]; P < 0.001) cultures in children with CF compared to a control group. The first site of S. aureus detection was the nose in 6 patients and the oropharynx in 14 patients, respectively. Longitudinal analysis demonstrated a significantly higher S. aureus prevalence (61/62 [98%] versus 47/62 [76%]; P < 0.001) and persistence (46/62 [74%] versus 31/62 [50%]; P < 0.01) in the oropharynx than in the nose. In CF patients, the oropharynx, and not the nose, was the predominant site of S. aureus infection and persistence. Hence, it is unlikely that CF patients will benefit from topical treatment strategies to eradicate nasal carriage