Comparison of prophylactic regimens to prevent aspergillus infections in lung transplant recipients
Avasarala SK, Spagna P, Yessayan L, Rendulic T, Stagner L, Jennings J, Nemeh HW, and Allenspach L. Comparison of prophylactic regimens to prevent aspergillus infections in lung transplant recipients. Am J Respir Crit Care Med 2015; 191.
Am J Respir Crit Care Med
Lung transplantation is a lifesaving therapy for a variety of end stage lung diseases. However, infections remain a significant threat after lung transplantation; Aspergillus infections are a serious limitation to long term survival. Despite this, there is no defined prophylactic treatment strategy to prevent Aspergillus infection following lung transplantation. This single center retrospective cohort describes our experience with multiple regimens that were used to prevent the colonization with Aspergillus spp. after lung transplantation: no antifungal therapy (none), oral voriconazole for three months (voriconazole), and inhaled liposomal amphotericin B for six months (amphotericin). Methods: All consecutive patients that underwent lung transplantation at an urban academic teaching hospital from 2003 through 2013 were screened for eligibility (n = 108). Patients who were colonized at baseline and those who had multiple treatment strategies (crossover) before first colonization were excluded. All fungal cultures from bronchoalveolar lavages and bronchial washings for the first two years following transplantation (or death within two years) were assessed. A total of 79 patients were analyzed in groups determined by their initial prophylactic regimen: none (n=32), voriconazole (n = 12), and amphotericin (n = 35). The event-free survival from colonization in the 31-730 days after transplant (post-transplant period) was calculated by the Kaplan-Meier product limit estimator and survival curves were compared using the log-rank test. Results: The study was underpowered to detect statistically significant differences among the three different prophylactic groups. There were no differences in time to colonization with Aspergillus spp. in lung transplant recipients among the groups in post-transplant period. Although not statistically significant, the point estimate for the hazard ratio for colonization in the post-transplant period was lower with voriconazole when compared to either amphotericin (hazard ratio [HR] = 0.669, p = 0.5542) or none (HR = 0.746, p = 0.6648). A Kaplan-Meier survival curve comparing the three groups is depicted in Figure 1. Conclusions: Although more expensive and more likely to induce drug interactions with immunosuppressive medications, voriconazole may be more effective than amphotericin in preventing colonization with Aspergillus spp. in lung transplant patients in the first two years following transplantation. One advantage of oral voriconazole over inhaled amphotericin is ease of use. Due to a limitation in sample size and bias by indication, a dedicated randomized control trial is needed to determine the optimal prophylactic regimen in this patient group. (Figure Presented).