The Effect of Strict Segregation on Pseudomonas aeruginosa in Cystic Fibrosis Patients

Abstract

Introduction: Segregation of patients with cystic fibrosis (CF) was implemented to prevent chronic infection with epidemic Pseudomonas aeruginosa strains with presumed detrimental clinical effects, but its effectiveness has not been carefully evaluated.

Methods: The effect of strict segregation on the incidence of P. aeruginosa infection in CF patients was investigated through longitudinal protocolized follow-up of respiratory tract infection before and after segregation. In two nested cross-sectional studies in 2007 and 2011 the P. aeruginosa population structure was investigated and clinical parameters were determined in patients with and without infection with the Dutch epidemic P. aeruginosa clone (ST406).

Results: Of 784 included patients 315 and 382 were at risk for acquiring chronic P. aeruginosa infection before and after segregation. Acquisition rates were, respectively, 0.14 and 0.05 per 1,000 days at risk (HR: 0.66, 95% CI [0.2548-1.541]; p = 0.28). An exploratory subgroup analysis indicated lower acquisition after segregation in children < 15 years of age (HR: 0.43, 95% CI[0.21-0.95]; p = 0.04). P. aeruginosa population structure did not change after segregation and ST406 was not associated with lung function decline, death or lung transplantation.

Conclusions: Strict segregation was not associated with a statistically significant lower acquisition of chronic P. aeruginosa infection and ST406 was not associated with adverse clinical outcome. After segregation there were no new acquisitions of ST406. In an unplanned exploratory analysis chronic acquisition of P. aeruginosa was lower after implementation of segregation in patients under 15 years of age.

Fig 1. Distribution of P. aeruginosa genotypes.

Distribution of 163 P. aeruginosa STs detected in 265 Dutch CF patients in 2007 and 49 patients with acquisition after segregation in 2011 among defined source groups. The 41 STs detected in 49 patients with acquired infection during segregation are indicated in blue and STs detected in the cross-sectional study in 2007 are depicted in red. Each circle represents an ST and size of circles represents number of isolates. Dotted circles enclose defined source groups. Assignment of STs to source groups is based on source group definition of STs, contained in the international pseudomonas MLST database (http://pubmlst.org/paeruginosa/), that are identical to the 163 STs identified in Dutch CF patients.

Fig 2. Survival free of lung transplantation or death.

Survival free of lung transplantation or death for CF patients with ST406 and CF patients with other P. aeruginosa clones (total n = 219, lung transplantation n = 11, died n = 14).