Pseudomonas aeruginosa eradication therapy and risk of acquiring Aspergillus in young children with cystic fibrosis

Thorax. 2019 Aug;74(8):740-748. doi: 10.1136/thoraxjnl-2018-211548. Epub 2019 Jun 15.

Abstract

Background: While Aspergillus detection rates in adults, adolescents and older children with cystic fibrosis (CF) have increased, the risk of acquiring this fungal pathogen in young children is unknown.

Aim: To determine the risk and explanatory factors of acquiring Aspergillus in children with CF by age 5 years.

Methods: Cross-sectional analysis of clinical, bronchoalveolar lavage and treatment data from the Australasian Cystic Fibrosis Bronchoalveolar Lavage study was used to identify predictive factors for detecting Aspergillus at age 5 years. A parametric repeated time-to-event model quantitatively described the risk and factors associated with acquiring Aspergillus and Pseudomonas aeruginosa from birth until age 5 years.

Results: Cross-sectional analysis found that the number of P. aeruginosa eradication courses increased the odds of detecting Aspergillus at age 5 years (OR 1.61, 95% CI 1.23 to 2.12). The median (IQR) age for the first P. aeruginosa positive culture was 2.38 (1.32-3.79) years and 3.69 (1.68-4.74) years for the first Aspergillus positive culture. The risk of P. aeruginosa and Aspergillus events changes with time after the first year of study entry. It also decreases for P. aeruginosa after completing P. aeruginosa eradication (HR 0.15, 95% CI 0.00 to 0.79), but increases for Aspergillus events (HR 2.75, 95% CI 1.45 to 5.41). The risk of acquiring both types of events increases after having had a previous event.

Conclusion: In young children with CF, completing P. aeruginosa eradication therapy and previous Aspergillus events are associated with increased risk of acquiring Aspergillus.

Keywords: Aspergillus; Pseudomonas aeruginosa eradication therapy; hazard; interval-censoring; repeated time-to-event analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / therapeutic use*
  • Bronchoalveolar Lavage
  • Ceftazidime / therapeutic use
  • Child, Preschool
  • Ciprofloxacin / therapeutic use
  • Clavulanic Acids / therapeutic use
  • Cross-Sectional Studies
  • Cystic Fibrosis / complications*
  • Female
  • Humans
  • Infant
  • Longitudinal Studies
  • Male
  • Prevalence
  • Pseudomonas Infections / drug therapy*
  • Pseudomonas Infections / epidemiology*
  • Pseudomonas aeruginosa*
  • Pulmonary Aspergillosis / diagnosis
  • Pulmonary Aspergillosis / epidemiology*
  • Randomized Controlled Trials as Topic
  • Recurrence
  • Risk Factors
  • Ticarcillin / therapeutic use
  • Tobramycin / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Clavulanic Acids
  • Ciprofloxacin
  • ticarcillin-clavulanic acid
  • Ceftazidime
  • Ticarcillin
  • Tobramycin