Epidemiology of fungal infection after lung transplantation

Abstract

Lung transplant recipients (LTRs) are at substantial risk for opportunistic infections, of which fungal infections are among the most significant. However, no consensus has been reached on anti fungal therapy initiation and duration after lung transplantation (LTx). Besides, the study of fungal infection in this study site had not been investigated. This study aimed to assess the epidemiology of fungus positive respiratory samples (FPRS) and invasive fungal diseases (IFDs) within one year after LTx in a single tertiary center in Korea and to evaluate the effectiveness of our antifungal prophylaxis after LTx. Among 242 LTRs, 102 (42.3% of the LTx registry) patients presented FPRS within one year after LTx. Candida spp. were cultured in 85 (32.4%) episodes and a median of 31.5 days after LTx, whereas Aspergillus spp. were cult ured in 29 (11.5%) episodes of 111. 4 days after LTx. 90 (37.2% of the LTx registry) patients developed invasive fungal diseases (IFDs) usually presented as tracheobronchitis, pneumonia, and disseminated fungal infection. Risk factors associated with developing invasive fungal disease included old age (OR 1.04; 95% CI 1.01 1.07), connective tissue disease associated interstitial lung disease (OR 10.43; 95% CI 2.52 43.21), previous use of antifungal agents (OR 2.53; 95% CI 0.96 6.62) and hospitalization days (OR 1.01; 95% CI 1.00 1.01). Most of the species causing IFDs were either Candida spp. or Aspergillus spp. and the median duration from the date of transplant surgery to the date of first invasive fungal disease was 33 days in Candida group and 103 days in Aspergillus group. IFD group had lower survival outcomes than the non IFD group (log rank p = 0.009). 93 % (93/100) of IFDs showed breakthrough infection, and one year mortality of IFDs was 44% (44/100). Use of itraconazole as antifungal prophylaxis that provides broad spectrum antifungal activity in our institution lowered the incidence rate of fungal colonization but did not decrease the incidence rate of IFDs. Sub-therapeutic drug serum levels might lead to breakthrough infection. Besides, multidrug-resistant C. glabrata and C. auris attributed treatment failure and increased mortality. Since fungal prophylaxis is essential to the high risk group, close inspection of bronchoscopy, prompt fungus culture, and appropriate use of antifungal therapies are h ighly recommended during the first year after lung transplantation. Although this single center study could not be generalized to transplant centers with different fungal epidemiology or immunosuppression and prophylactic agents , it is the first study describing the epidemiology of fungal infection during the first year of LTx in a tertiary hospital in South Korea. This study would contribute to the strategies of fungal infection treatment for LTRs.