Late Onset Invasive Pulmonary Aspergillosis in Lung Transplant Recipients in the Setting of a Targeted Prophylaxis/Preemptive Antifungal Therapy Strategy.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) is a significant cause of morbidity and mortality in lung transplant recipients (LTRs). It is unclear how a targeted prophylaxis/ preemptive antifungal therapy strategy impacts the incidence of IPA beyond the first-year posttransplant. METHODS: This is a retrospective cohort of LTRs from January 2010 to December 2014. We included all LTRs who survived beyond the first year, and followed them until death or 4 years postoperatively. Incidence of probable/proven IPA and Aspergillus colonization were assessed as per ISHLT criteria. Patients with risk factors, positive Aspergillus cultures, and/or galactomannan (GM) received targeted prophylaxis/ preemptive therapy within the first-year posttransplant. RESULTS: During the study period, 350 consecutive LTRs underwent 1078 bronchoscopies. Positive bronchoalveolar lavage for GM and/or Aspergillus cultures was reported for 15% (52/350) of LTRs between 2 and 4 years after transplantation. Among them, the median time to positive Aspergillus culture or GM positivity was 703 days (IQR 529-754). The incidence rate of IPA and Aspergillus colonization was 30/1000 patient-years, and 63/1000 patient-years respectively. The mortality rate was significantly higher in patients with IPA than without IPA (107/1000 patients-years vs. 18/1000 patient-years; p<0.0001). Rate of first year colonization and IPA was 33% and 9% respectively. Among the 201 patients who had a negative bronchoscopy during the 1 year posttransplant, only 6 (3%) developed IPA during the follow-up. CONCLUSION: A targeted prophylaxis/ preemptive therapy strategy within the first-year posttransplant resulted in 4% incidence of IPA at 4-years after transplantation. However, IPA was associated with higher mortality.