epiglucan and Cystic-Fibrosis

Aspergillus fumigatus is frequently encountered in sputum samples of patients with cystic fibrosis (CF), which traditionally has been interpreted as saprophytic airway colonization. However, this mere bystander role has been challenged by recent data. There is now evidence that Aspergillus fumigatus accelerates the decline of pulmonary function. (1→3)-β-D-glucan (BDG) and galactomannan (GM) are highly sensitive fungal biomarkers that are used to diagnose invasive fungal disease. However, their diagnostic value in CF patients is largely unknown.. We conducted a retrospective cohort study on 104 CF patients to determine whether serum BDG and GM levels correlate with parameters such as Aspergillus-positive sputum cultures and lung function.. Aspergillus fumigatus was persistently detected in 22 of the 104 CF patients (21%). Mean serum BDG and GM levels in the Aspergillus-positive patients were significantly higher than in those without persistent Aspergillus detection (89 versus 40 pg/ml [p = 0.022] and 0.30 versus 0.15 ODI [p = 0.013], respectively). 27 and 7 patients had elevated BDG (≥ 60 pg/ml) or GM levels (> 0.5 ODI), respectivly. BDG and GM levels showed a significant correlation (p = 0.004). Patients with increased serum concentrations of BDG were more frequently Aspergillus-positive (40.7 versus 14.3%, p = 0.004) and had a significantly lower forced expiratory volume in one second (FEV1) than patients with a normal BDG (61.6 versus 77.1%, p = 0.007). In the multivariate analysis, BDG but not GM or the growth of A. fumigatus, proved to be an independent predictor for the FEV1.. CF patients with persistent Aspergillus detection have elevated BDG and GM levels which ranged between healthy and invasively infected patients. Serum BDG may be superior to GM and fungal culture in predicting an impaired lung function in CF patients.

Topics: Adolescent; Adult; Aspergillus fumigatus; beta-Glucans; Case-Control Studies; Child; Child, Preschool; Cohort Studies; Culture Techniques; Cystic Fibrosis; Female; Forced Expiratory Volume; Galactose; Humans; Male; Mannans; Middle Aged; Multivariate Analysis; Proteoglycans; Pulmonary Aspergillosis; Retrospective Studies; Sputum; Young Adult

β-(1,3)-d-glucan (BDG) is used to rule out invasive fungal disease (IFD) but its usefulness in cystic fibrosis (CF) has not been evaluated. We measured serum BDG in CF patients with no clinical suspicion of IFD. Samples from 46 adult CF patients during a stable period and during pulmonary exacerbation were tested. The association of BDG with clinical variables was analyzed. Three hundred and three non-CF patients with suspected IFD were used as comparators. Both samples were negative in 52% of CF patients, whereas 67% of comparators had only negative results (P=0.08). CF patients with pancreatic insufficiency and CF-related diabetes had fewer negative results (P<0.05 for both). Negative results were more common in older CF patients (P<0.05). Use of antibiotics, presence of fungi in sputum and CF liver disease did not impact BDG levels. In conclusion, patients with CF experience significant BDG antigenaemia in the absence of IFD.

Topics: Adult; Aged; beta-Glucans; Cystic Fibrosis; Female; Humans; Male; Middle Aged; Mycoses; Serum; Young Adult

Various fungi have the ability to colonize surfaces and to form biofilms. Fungal biofilm-associated infections are frequently refractory to targeted treatment because of resistance to antifungal drugs. One fungus that frequently colonises the respiratory tract of cystic fibrosis (CF) patients is the opportunistic black yeast-like fungus Exophiala dermatitidis. We investigated the biofilm-forming ability of E. dermatitidis and its susceptibility to various antiinfective agents and natural compounds. We tested 58 E. dermatitidis isolates with a biofilm assay based on crystal violet staining. In addition, we used three isolates to examine the antibiofilm activity of voriconazole, micafungin, colistin, farnesol, and the plant derivatives 1,2,3,4,6-penta-O-galloyl-b-D-glucopyranose (PGG) and epigallocatechin-3-gallate (EGCG) with an XTT reduction assay. We analysed the effect of the agents on cell to surface adhesion, biofilm formation, and the mature biofilm. The biofilms were also investigated by confocal laser scan microscopy. We found that E. dermatitidis builds biofilm in a strain-specific manner. Invasive E. dermatitidis isolates form most biomass in biofilm. The antiinfective agents and the natural compounds exhibited poor antibiofilm activity. The greatest impact of the compounds was detected when they were added prior cell adhesion. These findings suggest that prevention may be more effective than treatment of biofilm-associated E. dermatitidis infections.

Topics: Antifungal Agents; Bacterial Adhesion; beta-Glucans; Biofilms; Catechin; Colistin; Cystic Fibrosis; Echinocandins; Exophiala; Farnesol; Humans; Lipopeptides; Micafungin; Microbial Sensitivity Tests; Mycoses; Voriconazole

Burkholderia cepacia complex (Bcc) organisms produce a wide variety of potential virulence factors, including exopolysaccharides (EPS), and exhibit intrinsic resistance towards many antibiotics. In the present study we investigated the contribution of Bcc biofilm matrix components, including extracellular DNA, cepacian and poly-β-1,6-N-acetylglucosamine, to tobramycin susceptibility.. The in vitro bactericidal activity of tobramycin in combination with recombinant human DNase (rhDNase), NaClO and dispersin B was tested against Bcc biofilms.. EPS degradation by NaClO pretreatment and specific PNAG degradation by dispersin B significantly increased the bactericidal effect of tobramycin towards some of the Bcc biofilms tested, including the strains of Burkholderia cenocepacia, B. cepacia and Burkholderia metallica. The presence of rhDNase during biofilm treatment and/or development had no influence on tobramycin activity.. These results suggest that EPS play a role in tobramycin susceptibility of Bcc biofilms and that matrix degrading combination therapy could improve treatment of Bcc biofilm infections.

Topics: Anti-Bacterial Agents; beta-Glucans; Biofilms; Burkholderia cepacia; Burkholderia Infections; Cystic Fibrosis; DNA, Bacterial; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Polysaccharides, Bacterial; Tobramycin; Virulence; Virulence Factors

Invasive pulmonary aspergillosis is a rare and fatal complication in patients with cystic fibrosis (CF) who lack concomitant risk factors. The few documented cases in children have all resulted in deaths during hospitalisation. We present the case of a 12-year-old boy with CF who was admitted for an exacerbation which was unresponsive to antibiotic therapy. The findings on imaging raised concerns about a possible fungal infection. As a result, voriconazole therapy was started prior to his respiratory deterioration. He was later found to be β-D glucan and Aspergillus Ag galactomannan positive confirming the suspicion for invasive pulmonary aspergillosis. Three months after diagnosis, he was discharged home under stable condition. Voriconazole was continued beyond discharge and resulted in improvement of respiratory symptoms. This underscores the importance of early treatment of pulmonary aspergillosis in patients with CF. Unfortunately, the patient died 6 months after diagnosis from a CF exacerbation.

Topics: Antifungal Agents; beta-Glucans; Biomarkers; Bronchoalveolar Lavage; Child; Cystic Fibrosis; Early Diagnosis; Fatal Outcome; Galactose; Humans; Immunocompromised Host; Invasive Pulmonary Aspergillosis; Male; Mannans; Pyrimidines; Triazoles; Voriconazole

Opportunistic fungal infections are life threatening especially for immunosuppressed patients. Early and accurate diagnosis is very important for the prompt initiation of treatment and to reduce unnecessary use of antifungal drugs. In recent years, efforts providing more rapid and more sensitive diagnosis of invasive fungal infections have been increasing. These methods include detection of fungal antigens, specific antibodies, fungal metabolites and DNA in the clinical samples. In this case, we report a seven year-old male patient with cystic fibrosis and diffuse large B-cell lymphoma, who presented with fever, vomiting and chronic cough. Diffuse parenchymal infiltrations and alveolar opacities in the inferior lobe of right lung and focal patchy alveolar infiltrates in different segments in both lungs were seen in thoracal CT scanning. Bronchoalveolar lavage (BAL) sample obtained by bronchoscopy was sent to the mycology laboratory and hypha elements that were compatible with Aspergillus were seen in direct examination. Aspergillus fumigatus was isolated from the culture of BAL sample. Real-time polymerase chain reaction (Rt-PCR), galactomannan (GM = 1.08 ng/ml) and 1,3-ß-D-Glucan (BG > 523 pg/ml) tests in BAL sample yielded positive results, however simultaneously performed PCR, GM (0.13 ng/ml) and BG (< 7 pg/ml) tests in serum sample were found to be negative. Treatment with voriconazole was started and continued for 45 days. The patient was discharged after improvement of his general state. It was concluded that PCR, GM and BG tests performed both in sera and BAL samples might aid to the early diagnosis and treatment of patients with invasive fungal infections in immunosuppressed patients. These data should be supported with further larger scale studies.

Topics: Antifungal Agents; beta-Glucans; Bronchoalveolar Lavage Fluid; Bronchoscopy; Child; Cystic Fibrosis; Galactose; Humans; Immunocompromised Host; Invasive Pulmonary Aspergillosis; Lymphoma, Large B-Cell, Diffuse; Male; Mannans; Pyrimidines; Real-Time Polymerase Chain Reaction; Tomography, X-Ray Computed; Triazoles; Voriconazole