Prophylactic Azithromycin Therapy After Lung Transplantation: Post hoc Analysis of a Randomized Controlled Trial

Am J Transplant. 2016 Jan;16(1):254-61. doi: 10.1111/ajt.13417. Epub 2015 Aug 4.

Abstract

Prophylactic azithromycin treatment has been demonstrated to improve freedom from bronchiolitis obliterans syndrome (BOS) 2 years after lung transplantation (LTx). In the current study, we re-evaluated the long-term effects of this prophylactic approach in view of the updated classification system for chronic lung allograft dysfunction (CLAD). A retrospective, intention-to-treat analysis of a randomized controlled trial comparing prophylactic treatment with placebo (n = 43) versus azithromycin (n = 40) after LTx was performed. Graft dysfunction (CLAD), graft loss (retransplantation, mortality), evolution of pulmonary function and functional exercise capacity were analyzed 7 years after inclusion of the last study subject. Following LTx, 22/43 (51%) patients of the placebo group and 11/40 (28%) patients of the azithromycin group ever developed CLAD (p = 0.043). CLAD-free survival was significantly longer in the azithromycin group (p = 0.024). No difference was present in proportion of obstructive versus restrictive CLAD between both groups. Graft loss was similar in both groups: 23/43 (53%) versus 16/40 (40%) patients (p = 0.27). Long-term pulmonary function and functional exercise capacity were significantly better in the azithromycin group (p < 0.05). Prophylactic azithromycin therapy reduces long-term CLAD prevalence and improves CLAD-free survival, pulmonary function, and functional exercise capacity after LTx.

Trial registration: ClinicalTrials.gov NCT01009619.

Keywords: (allograft) function/dysfunction; bronchiolitis obliterans (BOS); clinical research/practice; lung; lung failure/injury; lung transplantation/pulmonology; preventive healthcare; rejection: chronic.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / therapeutic use
  • Antibiotic Prophylaxis*
  • Azithromycin / therapeutic use*
  • Bacteremia / drug therapy*
  • Bacteremia / microbiology
  • Bronchiolitis Obliterans / complications
  • Bronchiolitis Obliterans / surgery*
  • Cohort Studies
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Forced Expiratory Volume
  • Graft Rejection / drug therapy*
  • Graft Rejection / etiology
  • Graft Rejection / pathology
  • Graft Survival
  • Humans
  • Lung Transplantation / adverse effects*
  • Male
  • Postoperative Complications
  • Prognosis
  • Risk Factors
  • Syndrome
  • Transplantation, Homologous

Substances

  • Anti-Bacterial Agents
  • Azithromycin

Associated data

  • ClinicalTrials.gov/NCT01009619