Clinical Outcomes Associated with Burkholderia cepacia Complex Infection in Patients with Cystic Fibrosis

Rationale: Little is known in contemporary cystic fibrosis (CF) cohorts about the outcomes after new Burkholderia species infections. Objectives: To evaluate the changing epidemiology and clinical outcomes associated with Burkholderia species infections in persons with CF. Methods: A cohort study of children and adults with CF was conducted from 1997 to 2018 in Toronto, Canada. Patients were characterized as those with no history of Burkholderia species infection and as those who were culture-positive for Burkholderia species for the first time in this time frame and were categorized by species (B. gladioli, B. cenocepacia, B. multivorans, or other) and strain (B. cenocepacia ET-12). Cox models were used to estimate the risk of death or transplantation. Mixed-effects models were used to assess the impact of Burkholderia species on odds of pulmonary exacerbations and effect on lung function (percentage predicted forced expiratory volume in 1 second [FEV1]). Results: A total of 1,196 patients were followed over 20 years; 88 patients (7.4%) had one or more culture-positive for Burkholderia species. Patients with ET-12 infection had a median time to death of 1.95 years compared with 5.30-6.72 years for those with other Burkholderia infections. ET-12 infection was associated with a greater risk of death or transplantation compared with patients with no history of Burkholderia infection in a univariate model (hazard ratio, 3.92; 95% confidence interval 2.25-6.81) but was no longer significant after adjusting for confounders. Pulmonary exacerbations were more common in those with Burkholderia infections and remained significant in the ET-12 group after adjusting for confounders (odds ratio, 2.96; 95% confidence interval, 1.17-7.53). No differences were noted in baseline FEV1% or the rate of FEV1% decline between the groups with and without Burkholderia species infection. Conclusions: With the exception of ET-12, the acquisition of Burkholderia species infection did not appear to worsen clinical outcomes compared with those with no history of infection. Given this, prognosis, management and clinical trial inclusion protocols may need to be reevaluated for persons with Burkholderia infection.