Association between MRSA Colonization and Chronic Lung Allograft Dysfunction in Lung Transplantation for Cystic Fibrosis

Abstract

Incidence of and risk factors for chronic lung allograft dysfunction (CLAD) in lung transplantation for cystic fibrosis (CF) are not established. Methicillin resistant staphylococcus aureus (MRSA) is associated with CF morbidity but its association with CLAD is unclear. We aimed to describe CLAD incidence and assess if pre-transplant MRSA colonization is associated with CLAD. Retrospective cohort analysis of patients receiving a lung transplant for CF from 6/2005-3/2018 at the University of Pittsburgh Medical Center. Patients with Burkholderia species were excluded. Colonization was defined as at least one positive culture in the year before transplant. CLAD was defined by ISHLT criteria. We used competing risks methods to estimate CLAD incidence and assess associations between MRSA and CLAD. Of 101 patients 34% were colonized with MRSA (n=34), 87% with Pseudomonas (n=88), and 31% with Aspergillus (n=31). Median post-transplant survival was 10.8 years and did not differ by MRSA colonization (p=0.50). CLAD incidence was 25% (95% CI 16-35%) at 5 years and 37% (95% CI 27-52%) at 10 years. BOS accounted for 74% (n=20/27) of cases, RAS 22% (n=6/27), and there was 1 mixed phenotype. CLAD incidence at 5 years was 45% (95% CI 25-62%) for MRSA colonized vs 18% (95% CI 9-29%) for non-colonized patients (Figure 1). Adjusting for established CLAD risk factors and co-colonization with Pseudomonas and Aspergillus, MRSA was associated with increased incidence of CLAD (SDH 2.53, 95% CI 1.16-5.51). Among 6-month survivors, MRSA colonization was associated with increased incidence of CLAD (SDH 2.66, 95% CI 1.03-6.88) adjusting for episodes of acute cellular rejection and recurrence of pre-transplant organisms. Incidence of CLAD in our cohort of CF recipients is low and varies by pre-transplant microbiota. MRSA colonization may be a risk factor for CLAD, perhaps reflecting differences in microbiome composition and associated host-microbiome interactions.