A prospective bacterial whole-genome-sequencing-based surveillance programme for comprehensive early detection of healthcare-associated infection transmission in paediatric oncology patients

Abstract

Bacterial whole-genome sequencing (WGS) and determination of genetic relatedness is an important tool for investigation of epidemiologically suspected outbreaks. This prospective cohort study evaluated a comprehensive, prospective bacterial WGS-based surveillance programme for early detection of transmission of most bacterial pathogens among patients at a paediatric oncology hospital. Cultured bacterial isolates from clinical diagnostic specimens collected prospectively from both inpatient and outpatient encounters between January 2019 and December 2021 underwent routine WGS and core genome multi-locus sequence typing to determine isolates' relatedness. Previously collected isolates from January to December 2018 were retrospectively analysed for identification of prior or ongoing transmission. Multi-patient clusters were investigated to identify potential transmission events based on temporal and spatial epidemiological links and interventions were introduced. A total of 1497 bacterial isolates from 1025 patients underwent WGS. A total of 259 genetically related clusters were detected, of which 18 (6.9%) multi-patient clusters involving 38 (3.7%) patients were identified. Sixteen clusters involved two patients each, and two clusters involved three patients. Following investigation, epidemiologically plausible transmission links were identified in five (27.8%) multi-patient clusters. None of the multi-patient clusters were suspected by conventional epidemiological surveillance. Bacterial WGS-based surveillance for early detection of hospital transmission detected several limited multi-patient clusters that were unrecognized by conventional epidemiological methods. Genomic surveillance helped efficiently focus interventions while reducing unnecessary investigations.