Twenty-five-year outbreak of Pseudomonas aeruginosa infecting individuals with cystic fibrosis: identification of the prairie epidemic strain

Abstract

Transmissible strains of Pseudomonas aeruginosa have been described for cystic fibrosis (CF) and may be associated with a worse prognosis. Using a comprehensive strain biobank spanning 3 decades, we sought to determine the prevalence and stability of chronic P. aeruginosa infection in an adult population. P. aeruginosa isolates from sputum samples collected at initial enrollment in our adult clinic and at the most recent clinic visit were examined by a combination of pulsed-field gel electrophoresis and multilocus sequence typing and compared against a collection of established transmissible and local non-CF bronchiectasis (nCFB) isolates. A total of 372 isolates from 107 patients, spanning 674 patient-years, including 66 patients with matched isolates from initial and final encounters, were screened. A novel clone with increased antibacterial resistance, termed the prairie epidemic strain (PES), was found in 29% (31/107 patients) of chronically infected patients referred from multiple prairie-based CF centers. This isolate was not found in those diagnosed with CF as adults or in a control population with nCFB. While 90% (60/66 patients) of patients had stable infection over a mean of 10.8 years, five patients experienced strain displacement of unique isolates, with PES occurring within 2 years of transitioning to adult care. PES has been present in our cohort since at least 1987, is unique to CF, generally establishes chronic infection during childhood, and has been found in patients at the time of transition of patients from multiple prairie-based CF clinics, suggesting broad endemicity. Studies are under way to evaluate the clinical implications of PES infection.

FIG 1

Patients included in the study. Of the 106 patients with chronic infection, 66 had matched first encounter (FE) and recent encounter (RE) isolates screened. Whereas PES isolates demonstrated stability over time, 12% of patients with unique (U) isolates experienced superinfections, predominately with PES. Genomic changes resulting in discrepant PFGE profiles of clonally related unique isolates were identified to have occurred in three instances, owing to apparent clonal relatedness by MLST.

FIG 2

PES represents a novel transmissible P. aeruginosa strain distinct from previously reported epidemic strains included in the strain collection. Only one isolate from each patient with PES is displayed, for the sake of simplicity. PES isolates share a 92% degree of similarity, whereas LES/strain A isolates share 86% similarity.

FIG 3

Nine patients had discrepant PFGE profiles between FE and RE samples. Superinfections can be seen to have occurred in six cases: five with PES and one with a new, unique strain. Three patients with significant differences in PFGE profiles still showed evidence of clonal relatedness by MLST. Samples are named as follows: patient ID (A number)/strain ID (P number)/date collected (month/day/year)-morphotype. n/a or N/A, samples that were unable to be amplified despite repeated attempts.

FIG 4

Longitudinal follow-up of a patient with P. aeruginosa CF isolates through 23 years. A single example of a PFGE profile is shown for a patient who acquired PES superinfection during follow-up at the CACFC, including all morphotypes from FE and RE samples and at least one isolate collected yearly in between. Samples are named as follows: patient ID-strain ID-date collected-morphotype.

FIG 5

Antibiotic nonsusceptibility of the isolates within the collection to four common antipseudomonal antibacterial agents. TSC, transmissible strain collection representing global strains other than LES/strain B.