Bacterial Re-Colonization Occurs Early after Lung Transplantation in Cystic Fibrosis Patients

Abstract

Most cystic fibrosis (CF) patients referred for lung transplantation are chronically infected with Gram-negative opportunistic pathogens. It is well known that chronic infections in CF patients have a significant impact on lung-function decline and survival before transplantation. The rate and timing of re-colonization after transplantation have been described, but the impact on survival after stratification of bacteria is not well elucidated. We did a single-center retrospective analysis of 99 consecutive CF patients who underwent lung transplantation since the beginning of the Copenhagen Lung Transplant program in 1992 until October 2014. Two patients were excluded due to re-transplantation. From the time of CF diagnosis, patients had monthly sputum cultures. After transplantation, CF-patients had bronchoscopy with bronchoalveolar lavage at 2, 4, 6 and 12 weeks and 6, 12, 18 and 24 months after transplantation, as well as sputum samples if relevant. Selected culture results prior to and after transplantation were stored. We focused on colonization with the most frequent bacteria: Pseudomonas aeruginosa (PA), Stenotrophomonas maltophilia (SM), Achromobacter xylosoxidans (AX) and Burkholderia cepacia complex (BCC). Pulsed-field gel electrophoresis (PFGE) was used to identify clonality of bacterial isolates obtained before and after lung transplantation. Time to re-colonization was defined as the time from transplantation to the first positive culture with the same species. Seventy-three out of 97 (75%) had sufficient culture data for analyses with a median of 7 (1-91) cultures available before and after transplantation. Median colonization-free survival time was 23 days until the first positive culture after transplantation. After 2 years, 59 patients (81%) were re-colonized, 33 (48.5%) with PA, 7 (10.3%) with SM, 12 (17.6%) with AX, and 7 (10.3%) with BCC. No difference in survival was observed between the patients colonized within the first 2 years and those not colonized. Re-colonization of bacteria in the lower airways occurred at a median of 23 days after transplantation in our cohort. In our patient cohort, survival was not influenced by re-colonization or bacterial species.

Keywords: colonization; cystic fibrosis; lung transplantation.

Figure 1

This diagram shows how patients were included and excluded in this study.

Figure 2

Kaplan–Meyer plot showing time from transplantation to re-colonization.

Figure 3

Pulsed-field-gel-electrophoresis pattern of 10 paired Achromobacter xylosoxidans isolates from bronchoalveolar lavage (BAL) fluid from five cystic fibrosis (CF) patients before and after lung transplantation (ltx). The Spe restriction enzyme was used. MW: molecular-weight standard. Lane 16 and 17: CF334 ML, before (lane16) and after ltx (lane 17). Lane 18 and 19: CF340 JP, before (lane 18) and after ltx (lane 19). Lane 20 and 21: CF353 ST, before (lane 20) and after ltx (lane 21). Lane 22 and 23: CF172 TN, before (lane 22) and after ltx (lane 23). Lane 24 and 25: CF347 HM, before (lane 24) and after ltx (lane 25).

Figure 4

(a,b) demonstrate the time CLAD and death after transplantation stratified for different bacteria.