Azithromycin Prophylaxis after Lung Transplantation is Associated with Improved Survival and Graft Function

Abstract

Azithromycin prophylaxis (AP) has been shown in a clinical trial to reduce the cumulative incidence of death or chronic lung allograft dysfunction (CLAD) onset in lung transplant recipients. However, there has been a lack of follow-up data on the long-term efficacy of this strategy in larger cohorts. Our program began using AP in 2010. Our objective was to evaluate the association between AP survival as well as CLAD and baseline lung allograft dysfunction (BLAD). We hypothesized that patients receiving AP would show equivalent survival and but reduced rates of CLAD and BLAD. We studied all double lung transplant recipients transplanted in our program between 2004-2016. We defined AP as any use of azithromycin prior to CLAD onset. The primary endpoint was death or retransplantation. We defined CLAD status, grade and subtype according to the 2019 ISHLT consensus criteria and BLAD in accordance with our previous published definition. We analyzed survival using proportional hazards regression with AP as a time-varying covariate, adjusting for recipient age, gender, transplant type, underlying diagnosis, year of transplant and induction. We used logistic regression to assess the relationship between AP and baseline allograft dysfunction (BLAD), defined as a failure to achieve both FEV1 and FVC ≥80% predicted on 2 consecutive tests ≥3 weeks apart. 445 patients were included and 344 (77%) were given AP with median time to azithromycin of 51 days [25th-75th quartile 20-211]. Patients receiving AP were more likely to receive induction with IL-2 receptor antagonists (57% vs. 35%; p<0.001) and had shorter mechanical ventilation (54 [29-150] vs. 96 [48-245] hours; p<0.001) and hospital stay (23 [18-36] days vs. 29 [19-44] days; p=0.016). AP was associated with improved survival (hazard ratio [HR] 0.60 [95% confidence interval [CI] 0.44-0.84]; p=0.002) in our adjusted model, as well as a reduced risk of CLAD onset (HR 0.64 [95% CI 0.44-0.94]; p=0.025) and reduced risk for BLAD (odds ratio 0.55 [95% CI 0.35-0.86]; p=0.009) in unadjusted models. Azithromycin prophylaxis is associated with improved survival after lung transplantation, possibly through improved baseline function and a reduced CLAD risk. This corroborates prior trial results, and suggest AP implementation would be beneficial for lung transplant recipients.