Concordance between epidemiological evaluation of probability of transmission and whole genome sequence relatedness among hospitalized patients acquiring Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae

Abstract

Objectives: We aimed to evaluate the concordance between epidemiologically determined transmission and genetic linkage of Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-Kp).

Methods: We included consecutive KPC-Kp carriers between December 2016 and April 2017 in a hospital endemic for KPC-Kp. We assessed epidemiological relatedness between patients by prospective investigations by the infection control team. The probability of epidemiological relatedness was classified into four groups: no suspected transmission, low, moderate and high probability of transmission. Whole-genome sequencing of isolates was performed. Genetic linkage between KPC-Kp isolates was expressed by distance between isolates in single nucleotide polymorphisms (SNPs). We established an SNP cut-off defining a different strain based on the reconstructed phylogenetic tree. We compared the epidemiological and genetic linkage of all isolates from all patients.

Results: The study included 25 KPC-Kp carriers with 49 isolates. SNP variance was available for 1129 crossed patient-isolate pairs. Genomic linkage, based on a cut-off of 80 SNPs to define related isolates, was found in 115/708 (16.2%) of isolates with no transmission suspected epidemiologically, 27/319 (8.5%) of low, 11/26 (42.3%) of moderate and 64/76 (84.2%) of high epidemiological transmission risk determination (p < 0.001 for trend). Similar results and significant trends were shown on sensitivity analyses using a lower SNP cut-off (six SNPs) and patient-isolate unique pairs, analysing the first isolate from each patient.

Conclusions: While significant concordance between epidemiological and genomic transmission patterns was found, epidemiological investigations of transmission are limited by the possibility of unidentified transmissions or over-estimation of associations. Genetic linkage analysis is an important aid to epidemiological transmission assessment.

Keywords: Carbapenem-resistant Enterobacterlaes; Colonization; Epidemiological infection investigation; Genomic linkage; Infection control; Single nucleotide polymorphisms; Transmission; Whole genome sequencing.