Effectiveness of rapid SARS-CoV-2 genome sequencing in supporting infection control for hospital-onset COVID-19 infection: Multicentre, prospective study.

Background: Viral sequencing of SARS-CoV-2 has been used for outbreak investigation, but there is limited evidence supporting routine use for infection prevention and control (IPC) within hospital settings. Methods: We conducted a prospective non-randomised trial of sequencing at 14 acute UK hospital trusts. Sites each had a 4-week baseline data collection period, followed by intervention periods comprising 8 weeks of 'rapid' (<48 hr) and 4 weeks of 'longer-turnaround' (5-10 days) sequencing using a sequence reporting tool (SRT). Data were collected on all hospital-onset COVID-19 infections (HOCIs; detected ≥48 hr from admission). The impact of the sequencing intervention on IPC knowledge and actions, and on the incidence of probable/definite hospital-acquired infections (HAIs), was evaluated. Results: A total of 2170 HOCI cases were recorded from October 2020 to April 2021, corresponding to a period of extreme strain on the health service, with sequence reports returned for 650/1320 (49.2%) during intervention phases. We did not detect a statistically significant change in weekly incidence of HAIs in longer-turnaround (incidence rate ratio 1.60, 95% CI 0.85-3.01; p=0.14) or rapid (0.85, 0.48-1.50; p=0.54) intervention phases compared to baseline phase. However, IPC practice was changed in 7.8 and 7.4% of all HOCI cases in rapid and longer-turnaround phases, respectively, and 17.2 and 11.6% of cases where the report was returned. In a 'per-protocol' sensitivity analysis, there was an impact on IPC actions in 20.7% of HOCI cases when the SRT report was returned within 5 days. Capacity to respond effectively to insights from sequencing was breached in most sites by the volume of cases and limited resources. Conclusions: While we did not demonstrate a direct impact of sequencing on the incidence of nosocomial transmission, our results suggest that sequencing can inform IPC response to HOCIs, particularly when returned within 5 days. Funding: COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) (grant code: MC_PC_19027), and Genome Research Limited, operating as the Wellcome Sanger Institute. Clinical trial number: NCT04405934.

Genomic surveillance detects Salmonella enterica serovar Paratyphi A harbouring blaCTX-M-15 from a traveller returning from Bangladesh.

Whole genome sequencing (WGS) has been used routinely by Public Health England (PHE) for identification, surveillance and monitoring of resistance determinants in referred Salmonella isolates since 2015. We report the first identified case of extended-spectrum-ß-lactamase (ESBL) Salmonella enterica serovar Paratyphi A (S. Paratyphi A) isolated from a traveller returning to England from Bangladesh in November 2017. The isolate (440915) was resistant to ciprofloxacin and harboured both the mobile element ISEcp9 -blaCTX-M-15-hp-tnpA and blaTEM-191, associated with ESBL production. Phenotypic resistance was subsequently confirmed by Antimicrobial Susceptibility Testing (AST). S. Paratyphi A 440915 harboured an IncI1 plasmid previously reported to encode ESBL elements in Enterobacteriaceae and recently described in a S. Typhi isolate from Bangladesh. Results from this study indicate the importance of monitoring imported drug resistance for typhoidal salmonellae as ceftriaxone is the first line antibiotic treatment for complicated enteric fever in England. We conclude that WGS provides a rapid, accurate method for surveillance of drug resistance genes in Salmonella, leading to the first reported case of ESBL producing S. Paratyphi A and continues to inform the national treatment guidelines for management of enteric fever.

High community faecal carriage rates of CTX-M ESBL-producing Escherichia coli in a specific population group in Birmingham, UK.

OBJECTIVES: To determine the proportion of E. coli carrying specific CTX-M extended-spectrum ß-lactamase (ESBL) genotypes in a community population of East and North Birmingham. METHODS: General practice and outpatient stool samples from 732 individuals submitted for examination for faecal pathogens in 2010 were screened for ESBL-producing E. coli using chromogenic agar. Multiplex PCR, denaturing HPLC, DNA sequencing and PFGE were used to determine the CTX-M genotype and clonal subtype. Isolates from people were assigned to 'Europe', 'Middle East/South Asia' (MESA) or 'uncategorized' groups using software to determine probable global origin based on the subject's full name. RESULTS: Prevalence of CTX-M carriage in the sample population was 11.3%. There was a statistically significant difference (P < 0.001) between carriage in the Europe group (8.1%) and the MESA group (22.8%). There was also a higher rate of carriage of CTX-M-15-producing E. coli (P < 0.001) in MESA subjects. CONCLUSIONS: The high community carriage rate and the significant difference in carriage between the Europe and MESA subjects may have important consequences for therapy. If the rising trend in carriage of bacteria producing ESBLs continues, guidelines for empirical therapy for patients presenting from the community may need to be modified. The findings also raise the concern that the pattern and routes of spread of CTX-M-15 may be replicated in the future by broader-spectrum ß-lactamases, such as New Delhi metallo-ß-lactamase ('NDM-1').