WGS data provided a robust and informative approach for monitoring MDR and emerging resistance to ciprofloxacin in Salmonella Typhi and Salmonella Paratyphi. Phenotypic antimicrobial susceptibility testing continues to be performed to guide targeted individual patient treatment, but inferred AMR profiles from WGS data may be used for surveillance and to guide empirical therapy.

Phenotypic and genome-derived AMR comparisons showed good correlation for EAEC. A better understanding of the role of allelic variants, specific gene combinations and promoter/attenuator mechanisms in the phenotypic manifestation will improve our ability to provide a robust interpretation of the data for surveillance purposes and, ultimately, in the clinical setting.

Introduction. Enteric fever (caused by Salmonella enterica serovars Typhi and Paratyphi) frequently presents as an acute, undifferentiated febrile illness in returning travellers, requiring timely empirical antibiotics. Gap Statement. Determining which empirical antibiotics to prescribe for enteric fever requires up-to-date knowledge of susceptibility patterns. Aim. By characterising factors associated with antimicrobial resistance in cases of S. Typhi and S. Paratyphi imported to England, we aim to guide effective empirical treatment. Methodology. All English isolates of S. Typhi and S. Paratyphi 2014–2019 underwent antimicrobial susceptibility testing; results were compared to a previous survey in London 2005–2012. Risk factors for antimicrobial resistance were analysed with logistic regression models to predict adjusted odds ratios (aOR) for resistance to individual antibiotics and multi-drug resistance. Results. We identified 1088 cases of S. Typhi, 729 S. Paratyphi A, 93 S. Paratyphi B, and one S. Paratyphi C. In total, 93 % were imported. Overall, 90 % of S. Typhi and 97 % of S. Paratyphi A isolates were resistant to ciprofloxacin; 26 % of S. Typhi were multidrug resistant to ciprofloxacin, amoxicillin, co-trimoxazole, and chloramphenicol (MDR+FQ). Of the isolates, 4 % of S. Typhi showed an extended drug resistance (XDR) phenotype of MDR+FQ plus resistance to third-generation cephalosporins, with cases of XDR rising sharply in recent years (none before 2017, one in 2017, six in 2018, 32 in 2019). For S. Typhi isolates, resistance to ciprofloxacin was associated with travel to Pakistan (aOR=32.0, 95 % CI: 15.4–66.4), India (aOR=21.8, 95 % CI: 11.6–41.2), and Bangladesh (aOR=6.2, 95 % CI: 2.8–13.6) compared to travel elsewhere, after adjusting for rising prevalence of resistance over time. MDR+FQ resistance in S. Typhi isolates was associated with travel to Pakistan (aOR=3.5, 95 % CI: 2.4–5.2) and less likely with travel to India (aOR=0.07, 95 % CI 0.04–0.15) compared to travel elsewhere. All XDR cases were imported from Pakistan. No isolate was resistant to azithromycin. Comparison with the 2005–2012 London survey indicates substantial increases in the prevalence of resistance of S. Typhi isolates to ciprofloxacin associated with travel to Pakistan (from 79–98 %) and Africa (from 12–60 %). Conclusion. Third-generation cephalosporins and azithromycin remain appropriate choices for empirical treatment of enteric fever in most returning travellers to the UK from endemic countries, except from Pakistan, where XDR represents a significant risk.

Objectives Shiga toxin-producing Escherichia coli (STEC) O157:H7 are zoonotic pathogens and transmission to humans occurs via contaminated food or contact with infected animals. The aim of this study was to describe the frequency, and distribution across the phylogeny, of antimicrobial resistance (AMR) determinants in STEC O157:H7 isolated from human cases in England. Methods Short-read whole-genome sequencing data from 1473 isolates of STEC O157:H7 from all seven sub-lineages (Ia-Ic, IIa-IIc and I/II) were mapped to genes known to confer phenotypic resistance to 10 different classes of antibiotic. Long-read sequencing was used to determine the location and genomic architecture of the AMR determinants within phylogenetic clusters exhibiting multidrug resistance. Results Overall, 216/1473 (14.7%) isolates had at least one AMR determinant, although the proportion of isolates exhibiting AMR varied by sub-lineage. The highest proportion of AMR determinants were detected in sub-lineages Ib (28/64, 43.7%), I/II (18/51, 35.3%) and IIc (122/440, 27.7%). In all sub-lineages, the most commonly detected AMR determinants conferred resistance to the aminoglycosides, tetracyclines and sulphonamides, while AMR determinants conferring resistance to fluroquinolones, macrolides and third-generation cephalosporins were rarely detected. Long-read sequencing analysis showed that the AMR determinants were co-located on the chromosome in sub-lineages Ib and lineage I/II, whereas those associated with sub-lineage IIc were encoded on the chromosome and/or large plasmids. Conclusions AMR genes were unevenly distributed across the different sub-lineages of STEC O157:H7 and between different clades within the same sub-lineage. Long-read sequencing facilitates tracking the transmission of AMR at the pathogen and mobile genetic element level.

Objectives Shiga toxin-producing Escherichia coli (STEC) are zoonotic pathogens that cause severe gastrointestinal disease in humans. Monitoring antimicrobial resistance (AMR) in STEC from symptomatic human cases may provide evidence for the extent of transmission of resistant strains and resistance genes from ruminants to humans. The aim of this study was to assess AMR in non-O157 STEC in England and Wales between 2014 and 2016, and to compare phenotypic and Whole Genome Sequencing (WGS) derived AMR profiles. Methods Six hundred and fifty-three non-O157 STEC isolates were analysed. WGS and bioinformatic analysis were performed on 457 isolates in the top 10 Clonal Complexes (CC) (193 were excluded on the basis of CC) and phenotypic susceptibility typing via breakpoint and minimum inhibitory concentration testing was undertaken on 100 isolates exhibiting resistance to at least one antimicrobial. Results Of 457 isolates, 332 lacked identifiable resistance genes and were predicted to be fully susceptible to 11 diverse classes of antimicrobials, 125 were found to carry one or more resistance genes and 83 were multi-drug resistant. Four isolates were identified as extended-spectrum b-lactamase-producers. In total, 46 different genes were detected – which conferred resistance to 8 different antibiotic classes. An overall concordance of 97.5  % was demonstrated between the two methods. Conclusions Phenotypic and genome-derived AMR comparisons showed good correlation for non-O157 STEC. This has added to the evidence base to support the use of genotypic approaches for antimicrobial susceptibility typing, to replace phenotypic typing for surveillance purposes, and guide clinical decision making in the more distant future.