A strategy for prevention of fungal infections in lung transplantation: Role of bronchoalveolar lavage fluid galactomannan and fungal culture

Background: The optimal strategy for prevention of invasive fungal infections in lung transplant recipients remains undetermined. We studied strategies based on bronchoalveolar lavage fungal culture and galactomannan for prevention of invasive aspergillosis in lung transplant recipients. Methods: Consecutive lung transplant recipients were evaluated during the period January 2010 to September 2014. Rates of invasive aspergillosis and all-cause mortality were recorded at 1 year. Criteria established by the International Society for Heart and Lung Transplantation were used to define invasive fungal infections. Multivariate Cox regression analyses were performed to assess the outcomes of mortality and invasive aspergillosis. Results: A total of 519 lung transplant recipients with 3,077 bronchoscopies were included in our study. The cumulative incidence of fungal infections was 14% (75 of 519). Of these patients, 10.6% (54 of 519) developed Aspergillus-related clinical syndromes. Using multivariate analysis, pre-emptive therapy was associated with significantly lower rates of invasive aspergillosis at 1 year post-transplantation compared with no pre-emptive therapy (hazard ratio [HR] 0.23, 95% confidence interval [CI] 0.09 to 0.58). Pre-emptive therapy and invasive aspergillosis had similar mortality rates compared with no invasive aspergillosis, or negative culture and galactomannan at 1 year (HR 0.54, 95% CI 0.23 to 1.28; and HR 0.99, 95% CI 0.44 to 2.25, respectively). During follow-up, 50% (259 of 519) of patients were negative for galactomannan and Aspergillus culture in bronchoalveolar lavage, and did not receive anti-fungal treatment. Only 2 patients developed invasive aspergillosis in this cohort. Conclusions: Our study suggests that use of bronchoalveolar lavage culture and a galactomannan-directed pre-emptive approach significantly decreased the risk of invasive aspergillosis, allowing a 50% reduction in anti-fungal exposure compared with a universal prophylaxis approach, without affecting mortality at 1 year.