Is universal antifungal prophylaxis mandatory in adults after lung transplantation? A review and meta-analysis of observational studies.

Background: Lung transplant (LTX) recipients are at high risk of invasive Aspergillus infections (IAI). However, no randomized-controlled trials (RCT) or international guidelines on antifungal prophylaxis (AFP) in the LTX population exist. Methods: A meta-analysis was performed to determine whether AFP reduces the rate of IAI after LTX. A total of six eligible observational studies (five with no prophylaxis, one with targeted prophylaxis, three studies including heart/lung transplantation) with a total of 748 patients were included. Results: The pooled odds ratio (OR) for IAI (62 IFI in the intervention arm and 82 in the control group) was 0.234 (95% confidence interval [CI] 0.097-0.564, P=0.001, z=-3.237). Pooled studies were characterized by substantial heterogeneity (I-2=66.64%); number needed to treat was 6.8. A subgroup analyses with exclusion of heart transplant recipients also showed a statistically significant reduction in IAI with AFP (OR 0.183, 95% CI 0.0449-0.744, P=0.018). Conclusion: This study suggests that universal antifungal prophylaxes reduces incidence of IAI after LTX. However, included studies are limited by small sample size, single-center structure without randomization, mixed population (including heart/heart-lung transplant), and heterogeneity due to variations in immunosuppression, type, and duration of AFP. Therefore, there is a clear need for an adequately powered RCT.