Post-operative antifungal prophylaxis in lung transplant recipients: Unprecedented evidence

Abstract

Introduction/objectives Despite recent advances in lung transplantation, Aspergillus infections are still a major concern in lung transplant (LT) recipients. The genus Aspergillus may manifest as colonization or infection forms. The latter being associated with significant mortality and morbidity. Colonization, defined as bronchoalveolar lavage or bronchial aspirate, or positive bronchoalveolar lavage galactomannan test, or at least two positive sputum cultures, or tracheal aspirate for Aspergillus spp. in asymptomatic patients with normal-appearing respiratory mucosa or absence of endobronchial lesions, usually precedes infectious forms and complicates transplantation course. While several antifungal prophylactic strategies have been used to limit this deadly disease that mess with this complex endeavor, evidence from retrospective or prospective studies is lacking. In a recent international survey, only 50% of lung transplants’ centers use antifungal prophylaxis, yet, substantial differences regarding the duration and the modality of antifungal prophylaxis exist among centers and, hence, increase the unmet need for clear recommendations. Since airways’ colonization usually precedes Aspergillus infections and LT recipients are most vulnerable, in particular, during the early post-operative period due to anastomotic ischemia, Aspergillus’ eradication seems to be a plausible solution to prevent or minimize Aspergillus colonization/infections post-transplantation. Consequently, all patients who underwent single or double lung transplantation in our center after 2014 received antifungal prophylaxis started on day 1 post-transplantation and carried on till healing of bronchial anastomosis. We report our 4-year experience with antifungal prophylaxis in LT recipients. Methods A retrospective analysis was conducted and compared LT recipients who systematically received inhaled amphotericin B deoxycholate (6 mg twice daily) and 200 mg twice daily oral voriconazole (2014–2017) to those who did not (2008–2013). Only non-cystic fibrosis LT recipients were included in the analysis given that cystic fibrosis patients usually harbor aspergillus species in their sino-nasal/respiratory tract, a fact that may underestimate such therapeutic strategy benefit and Aspergillus’ eradication may not be achieved. The data showed in this analysis was traced till hospital discharge. Results A total of 142 non-cystic fibrosis patients had undergone single/double lung transplantation. Between 2014 and 2017, 59 LT recipients received antifungal prophylaxis and Aspergillus spp. was found in 20 patients (incidence of 33%), while in the control group (n = 83) Aspergillus spp. was recovered from 42 patients (incidence of 50%). The difference between these 2 groups was statistically significant (P = 0.04) suggesting a potential beneficial effect of prompt post-operative antifungal prophylaxis in reducing Aspergillus colonization. Aspergillus fumigatus, A. niger, and A. flavus were most commonly found. Conclusions Immediate post-operative antifungal prophylaxis using amphotericin B deoxycholate and oral voriconazole significantly reduced nosocomial Aspergillus colonization in non-cystic fibrosis LT recipients. A finding that might decrease subsequent Aspergillus related complications and reduce unnecessary morbidity. However, prospective controlled randomized trials with long-term follow-up are eagerly awaited.