The hazards of acquiring Aspergillus positive culture in children with cystic fibrosis

Background: Lung disease is a major cause of morbidity and mortality in patients with cystic fibrosis (CF). Impaired mucociliary clearance and host defence mechanisms in the airway lead to airway infections. From very young age, children with CF suffer infections with Pseudomonas aeruginosa (P. aeruginosa) and eradication therapy with antibiotic therapy is now standard care and has been shown to be effective (1). High use of antibiotics has been associated with acquiring positive respiratory cultures of Aspergillus species which are also associated with reduction in lung function (2). The hazard of acquiring Aspergillus as well as factors predicting acquisition are unknown.

Objective: To describe the hazard of Aspergillus positive culture in children with CF

Methods: Data from the Australasian CF Broncheoalveolar lavage study (ACFBAL) was used in this analysis (3). Newborns diagnosed with CF were followed till 5 years of age. Data on Aspergillus fumigatus (Af) acquisition collected from bronchoalveolar lavage in 80 patients who had recurrent BAL collection was used for the current analysis, providing a reliable method of detection (4). The hazards of having Af positive culture within the 5 years was described by fitting a parametric survival model to the data using NONMEM version 7.2. All event times were treated as either (i) exact times or (ii) interval censored. Models were evaluated using visual predictive check Kaplan-Meier curves.

Results: Of 80 patients, 36 had at least one positive Af culture in the first 5 years of age. Ten had 2 and 4 had a 3 positive cultures. The repeated time to event data were best described by a Gompertz distribution with parameters estimated independently for the first and for subsequent events. The hazard ratio (HR) for having an Af positive culture increased with time. Duration of tobramycin (intravenous and inhalation) had an influence on the hazards where it increased the HR for Af events.

Conclusion: The hazards of Af positive culture in young children with CF increased with time and was influenced by antibiotic use to eradicate P.aeruginosa. Evaluating the influence of antibiotic exposure on the hazards of Af acquisition are future steps.


1. Doring G, Flume P, Heijerman H, Elborn JS. Treatment of lung infection in patients with cystic fibrosis: current and future strategies. Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society. 2012;11(6):461-79.
2. Amin R, Dupuis A, Aaron SD, Ratjen F. The effect of chronic infection with Aspergillus fumigatus on lung function and hospitalization in patients with cystic fibrosis. Chest. 2010;137(1):171-6
3. Wainwright CE, Vidmar S, Armstrong DS, Byrnes CA, Carlin JB, Cheney J, et al. Effect of bronchoalveolar lavage-directed therapy on Pseudomonas aeruginosa infection and structural lung injury in children with cystic fibrosis: a randomized trial. JAMA : the journal of the American Medical Association. 2011;306(2):163-71.
4. Armstrong DS, Grimwood K, Carlin JB, Carzino R, Olinsky A, Phelan PD. Bronchoalveolar lavage or oropharyngeal cultures to identify lower respiratory pathogens in infants with cystic fibrosis. Pediatric pulmonology. 1996;21(5):267-75