Late Onset Invasive Pulmonary Aspergillosis in Lung Transplant Recipients Treated with a Preemptive/ Targeted Antifungal Therapy Strategy: 4 Year Follow Up

Abstract

Purpose Invasive pulmonary aspergillosis (IPA) is a significant cause of morbidity and mortality in lung transplant recipients (LTRs). Centers employing universal antifungal prophylaxis have reported up to 60% of the IPA episodes occur after the first year post transplant. We previously reported the incidence of IPA during the first year after transplant in a cohort of LTRs treated with preemptive prophylaxis. It is unclear how a preemptive/targeted antifungal therapy strategy impacts the incidence of IPA beyond 1 year post transplant. Methods Retrospective study of consecutive LTRs from 1 Jan 2010 to 31 Dec 2014 with a 4 year follow up on those who survived at least 1 year. Incidence of probable/ proven IPA, bronchoalveolar (BAL) Aspergillus spp. cultures or Galactomannan (GM) positivity (index value >1) were recorded during this period. IPA, Aspergillus colonization and preemptive/ targeted prophylaxis were defined according to criteria established by ISHLT. Patients with probable/ proven IPA, positive Aspergillus cultures and/ or GM received preemptive/ targeted therapy. Results There were a total of 350 consecutive LTRs with 1078 bronchoscopies . 82% (288/350) were double lung transplants, with median age of 53.9 yrs. 73% (254/350) LTRs did not receive induction immunosuppression with basiliximab or thymoglobulin . 15% (52/350) LTRs had positive BAL for GM and/ or Aspergillus cultures beyond 1 year of transplantation. Median time to positive Aspergillus culture or positive GM was 608 days. Figure 1 shows the distribution of positive Aspergillus culture and GM in the cohort after 1 year . 3% (10/350) LTRs met criteria for probable IPA. Beyond 1 year, none of the Aspergillus culture or GM negative patients had biopsy proven IPA. All cause mortality in LTRs with IPA was 10% (1/10). Conclusion Undergoing a preemptive strategy beyond 1 year post transplantation resulted in a low frequency of treatment for IPA when assessing positive BAL cultures or GM.