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Impact of Burkholderia Infection on Lung Transplantation in Cystic Fibrosis

¹ Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan; ² Scientific Registry of Transplant Recipients, Ann Arbor, Michigan; ³ Cystic Fibrosis Foundation, Bethesda, Maryland; ⁴ Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan; and ⁵ Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, Michigan

Correspondence and requests for reprints should be addressed to John J. LiPuma, M.D., University of Michigan, Department of Pediatrics, 1150 W. Medical Center Drive, 8323 MSRB III, 0646, Ann Arbor, MI 48109. E-mail: jlipuma{at}umich.edu

Rationale: Lung transplantation offers the only survival option for patients with cystic fibrosis (CF) with end-stage pulmonary disease. Infection with Burkholderia species is typically considered a contraindication to transplantation in CF. However, the risks posed by different Burkholderia species on transplantation outcomes are poorly defined.

Objectives: To quantify the risks of infection with Burkholderia species on survival before and after lung transplantation in patients with CF.

Methods: Multivariate Cox survival models assessed hazard ratios of infection with Burkholderia species in 1,026 lung transplant candidates and 528 lung transplant recipients. Lung allocation scores, incorporating Burkholderia infection status, were calculated for transplant candidates.

Measurements and Main Results: Transplant candidates infected with different Burkholderia species did not have statistically different mortality rates. Among transplant recipients infected with B. cenocepacia, only those infected with nonepidemic strains had significantly greater post-transplant mortality compared with uninfected patients (hazard ratio [HR], 2.52; 95% confidence interval [CI], 1.04–6.12; P = 0.04). Hazards were similar between uninfected transplant recipients and those infected with B. multivorans (HR, 0.66; 95% CI, 0.27–1.56; P = 0.34). Transplant recipients infected with B. gladioli had significantly greater post-transplant mortality than uninfected patients (HR, 2.23; 95% CI, 1.05–4.74; P = 0.04). Once hazards for species/strain were included, lung allocation scores of B. multivorans–infected transplant candidates were comparable to uninfected candidate scores, whereas those of candidates infected with nonepidemic B. cenocepacia or B. gladioli were lower.

Conclusions: Post-transplant mortality among patients with CF infected with Burkholderia varies by infecting species. This variability should be taken into account in evaluating lung transplantation candidates.

Key Words: infection • lung allocation • transplant benefit • Burkholderia

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Burkholderia infection is considered a contraindication to lung transplantation in cystic fibrosis. However, the risks posed by different Burkholderia species on outcomes after lung transplantation in cystic fibrosis are not well defined. What This Study Adds to the Field This multivariate analysis shows that the risk of poor outcome after lung transplantation varies between Burkholderia species. These relative risks should be taken into account in evaluating lung transplantation candidates.

 

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