Middleton MA, Layeghifard M, Klingel M, Stanojevic S, Yau YCW, Zlosnik JEA, Coriati A, Ratjen FA, Tullis ED, Stephenson A, Wilcox P, Freitag A, Chilvers M, McKinney M, Lavoie A, Wang PW, Guttman DS, Waters VJ
Ann Am Thorac Soc 2018 Jun;
PMID: 29911888
Abstract
RATIONALE: The extent of the genetic relatedness among Pseudomonas aeruginosa isolates and its impact on clinical outcomes in the cystic fibrosis (CF) population is poorly understood.
OBJECTIVES: The objectives of this study were to determine the prevalence of clonal P. aeruginosa infection in Canada and to associate P. aeruginosa genotypes with clinical outcomes.
METHODS: This was an observational study of adult and pediatric CF patients across Canada. Isolates were typed using multi-locus sequence typing (MLST). A clone was defined as sharing >6 of 7 alleles. Genotyping results were associated with clinical outcomes including forced expiratory volume in 1 second (FEV1), body mass index (BMI), rate of pulmonary exacerbation, and death/transplant.
RESULTS: 1,537 P. aeruginosa isolates were genotyped to 403 unique sequence types (STs) in 402 individuals with CF. Although 39% of STs were shared, most were shared only among a small number of subjects and the majority (79%) of the genetic diversity in P. aeruginosa isolates was observed between patients. There were no significant differences in clinical outcomes according to genotype. However, patients with a dynamic, changing ST infection pattern had both a steeper decline in FEV1 (-2.9% predicted change/yr, 95% CI -3.8, -1.9 compared to 0.4, 95% CI -0.3, 1.0) (p<0.001) and BMI (-1.0 percentile change/yr, 95% CI -1.6, -0.3 compared to -0.1, 95% CI -0.7, 0.5) (p=0.047) than those with a stable infection with the same ST.
CONCLUSIONS: There was no widespread sharing of dominant clones in our CF population, and the majority of the genetic diversity in P. aeruginosa was observed between patients. Changing genotypes over time within an individual was associated with worse clinical outcomes.