Persistence of Candida Dubliniensis in the Lower Airways of Cystic Fibrosis Patients

Abstract

BackgroundCystic fibrosis (CF) is a genetic disease affecting 70,000 individuals worldwide and results from mutations in the gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR). In the lungs, the mucociliary clearance mechanism is impaired and the airways of CF patients are often colonized by bacteria, yeasts and filamentous fungi. Among clinically significant fungi, Candida spp. are the most common yeasts but their prevalence rates vary greatly according to the different studies. It is still controversial as to whether Candida spp. are transient or persistent colonizers of the respiratory tract of CF patients. Candida dubliniensis is pathogenic yeast of the genus Candida which is phenotypically closely related to C. albicans. It is emerging yeast in the respiratory tract of patients with CF.Aims and objectivesTo determine the frequency of C. dubliniensis recovered from lower respiratory samples of CF patients and compare between pediatric ( ≤ 18 year) and adult (> 18 year) CF patients. The secondary objective was to evaluate whether CF patients have persistent C. dubliniensis isolated in their lower respiratory secretions.MethodsA prospective study of 52 CF patients (38 pediatric and 14 adult CF patients) over a period of 14 months. Each CF patient had at least two lower respiratory secretions either an outpatient or in-patient setting with interval 3–5 months between specimens during the study period. Sputum samples, deep pharyngeal swabs (taken from patients who did not produce sputum), and bronchoalveolar lavage (BAL) samples were collected and immediately delivered to the Mycology Laboratory at Hamad Medical Corporation, Doha, Qatar. Patients were excluded from the study if they had only one respiratory sample. Respiratory secretions were cultured for Candida species and identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). Clinical data including body mass index (BMI) and the FEV1% (the volume of air forcefully exhaled in one second and then converted to a percentage of normal) were collected. Descriptive statistics and unpaired t test were used to analyze the data using SPSS 21software.ResultsCandida isolates were obtained from 40 CF patients (76.9%). There were 56.2% (77/137) of respiratory specimens positive for Candida species. C dubliniensis was the most prevalent Candida sp. 65%(50/77) isolated from 29 CF patients more often from adults than children (91.3% vs 53.7%; respectively). Other Candida spp. isolated was C. albicans 27.2%(21/77), C. tropicalis 6.5%(5/77) and C. glabrata 1.3%(1/77). In CF patients, two or more Candida spp. were never isolated from the same respiratory specimen. During the study period, C. dubliniensis was isolated repeatedly in 11 (27.5%) CF patients and transient isolates were found in 13 (32.5%) patients. C. dubliniensis was recovered from the first respiratory specimen followed by other Candida spp. in subsequent samples in 5 (12.5%) patients. C. dubliniensis has no significant effect on BMI and the FEV1% during the study period in each persistent and intermittent C. dubliniensis group respectively (P>0.05). None of the CF patients received antifungal therapy. The prevalence of C. dubliniensis was higher in adults harboring Pseudomonas aeruginosa, while in pediatric patients C. dubliniensis coexisted with Staphylococcus aureus.ConclusionThe present study reports the high and frequent occurrence of C. dubliniensis from the lower respiratory secretions of CF patients and has no effect on both BMI and FEV1%.