*Purpose: Itraconazole (ITR) therapeutic drug monitoring (TDM) for prophylaxis in lung transplant recipients (LTR) is not well characterized. Our purpose was to evaluate ITR trough concentration and its association with identification of fungal pathogens.

*Methods: We conducted a retrospective study of adult LTR from 2014-2017. We collected data on clinical features, microbiology, and ITR TDM. Patients were initially administered 200mg oral solution per protocol. Association between ITR trough concentration and identified fungal pathogens was determined by comparing the incidence rate of positive bronchoalveolar lavage (BAL) fluid studies in LTR with at least 1 total ITR level ≥2 ug/mL to LTR with total ITR levels <2 ug/mL. Total ITR level was defined as the sum of ITR and Hydroxy-ITR, using Liquid Chromatography-Tandem Mass Spectrometry.

*Results: We identified 527 LTR on 388,000 days of ITR. 1,132 ITR trough concentrations were analyzed. We divided patients into 2 groups: group 1 had at least one level ≥2.0 (n=112 [21%]); and group 2 had all levels <2.0 (n=415 [79%]). There was marked inter- and intra-patient variability for both ITR and Hydroxy-ITR levels. Median ITR level at steady-state in group 1 was 2.0, significantly higher compared to 0.70 in group 2. Median duration of ITR was 730 days in group 1 and 580 days in group 2. The primary outcome was identification of a fungal pathogen in BAL fluid. 25 (22%) in group 1 were found to have a fungal pathogen compared to 127 (31%) in group 2. Median time to pathogen isolation was similar in the 2 groups: 115 vs. 90 days. Most fungal pathogens were Aspergillus species (76 vs. 67%, respectively, in groups 1 and 2). Overall rate of fungal pathogen identification was 0.39 per 1,000 patient days on ITR (95% CI 0.33-0.46). The rate in group 1 was 0.26 (95% CI 0.17-0.38), which was significantly lower than group 2 (0.43 [95% CI 0.36-0.51]). Having at least one ITR level ≥2.0 was associated with a statistically significant 39% reduction in rate of fungal pathogen identification (rate ratio 0.61 [95% CI 0.39-0.92]; p=0.02). 1-year all-cause mortality was significantly lower in group 1 (4 vs. 13% [p=0.002]).

*Conclusions: Achieving ≥1 total ITR trough concentration ≥2.0 was associated with a decrease in the rate of identifying fungal pathogens in BAL fluid of LTR and improved survival. The optimal ITR level for prophylaxis in LTR is not well defined. Based on our data, we think that the total ITR is the most appropriate measure and a level of approximately 2 could be a reasonable target.

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