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

Abstract

ObjectivesWe aimed to evaluate the concordance between epidemiologically determined transmission and genetic linkage of Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-Kp). MethodsWe 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. ResultsThe 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. ConclusionsWhile 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.