Nationwide, population-based observational study of the molecular epidemiology and temporal trend of carbapenemase-producing Enterobacterales in Norway, 2015 to 2021

National and regional carbapenemaseproducing Enterobacterales (CPE) surveillance is essential to understand the burden of antimicrobial resistance, elucidate outbreaks, and develop infection-control or antimicrobial-treatment recommendations. Aim: This study aimed to describe CPE and their epidemiology in Norway from 2015 to 2021. Methods: A nationwide, population-based observational study of all verified clinical and carriage CPE isolates submitted to the national reference laboratory was conducted. Isolates were characterised by antimicrobial susceptibility testing, whole genome sequencing (WGS) and basic metadata. Annual CPE incidences were also estimated. Results: A total of 389 CPE isolates were identified from 332 patients of 63years median age (range:0–98). These corresponded to 341 cases, 184 (54%) being male. Between 2015 and 2021, the annual incidence of CPE cases increased from 0.6 to 1.1per 100,000person-years. For CPEisolates with available data on colonisation/infection, 58% (226/389)were associated with colonisation and 38% (149/389) with clinical infections. WGS revealed a predominance of OXA-48-like (51%; 198/389) and NDM (34%; 134/389) carbapenemases in a diversified population of Escherichia coli and Klebsiella pneumoniae, including high-risk clones also detected globally. Most CPE isolates were travel-related (63%;245/389). Although local outbreaks and healthcare-associated transmission occurred, no interregional spread was detected. Nevertheless, 18% (70/389) of isolates not directly related to import points towards potentially unidentified transmission routes. A decline in travelassociated cases was observed during the COVID-19 pandemic. Conclusions: The close-to-doubling of CPE case incidence between 2015 and 2021 was associated with foreign travel and genomic diversity. To limit further transmission and outbreaks, continued screening and monitoring is essential

Emergence and dissemination of antimicrobial resistance in Escherichia coli causing bloodstream infections in Norway in 2002-17: a nationwide, longitudinal, microbial population genomic study.

BACKGROUND: The clonal diversity underpinning trends in multidrug resistant Escherichia coli causing bloodstream infections remains uncertain. We aimed to determine the contribution of individual clones to resistance over time, using large-scale genomics-based molecular epidemiology. METHODS: This was a longitudinal, E coli population, genomic, cohort study that sampled isolates from 22 512 E coli bloodstream infections included in the Norwegian surveillance programme on resistant microbes (NORM) from 2002 to 2017. 15 of 22 laboratories were able to share their isolates, and the first 22·5% of isolates from each year were requested. We used whole genome sequencing to infer the population structure (PopPUNK), and we investigated the clade composition of the dominant multidrug resistant clonal complex (CC)131 using genetic markers previously reported for sequence type (ST)131, effective population size (BEAST), and presence of determinants of antimicrobial resistance (ARIBA, PointFinder, and ResFinder databases) over time. We compared these features between the 2002-10 and 2011-17 time periods. We also compared our results with those of a longitudinal study from the UK done between 2001 and 2011. FINDINGS: Of the 3500 isolates requested from the participating laboratories, 3397 (97·1%) were received, of which 3254 (95·8%) were successfully sequenced and included in the analysis. A significant increase in the number of multidrug resistant CC131 isolates from 71 (5·6%) of 1277 in 2002-10 to 207 (10·5%) of 1977 in 2011-17 (p<0·0001), was the largest clonal expansion. CC131 was the most common clone in extended-spectrum β-lactamase (ESBL)-positive isolates (75 [58·6%] of 128) and fluoroquinolone non-susceptible isolates (148 [39·2%] of 378). Within CC131, clade A increased in prevalence from 2002, whereas the global multidrug resistant clade C2 was not observed until 2007. Multiple de-novo acquisitions of both blaCTX-M ESBL-encoding genes in clades A and C1 and gain of phenotypic fluoroquinolone non-susceptibility across the clade A phylogeny were observed. We estimated that exponential increases in the effective population sizes of clades A, C1, and C2 occurred in the mid-2000s, and in clade B a decade earlier. The rate of increase in the estimated effective population size of clade A (Ne=3147) was nearly ten-times that of C2 (Ne=345), with clade A over-represented in Norwegian CC131 isolates (75 [27·0%] of 278) compared with the UK study (8 [5·4%] of 147 isolates). INTERPRETATION: The early and sustained establishment of predominantly antimicrobial susceptible CC131 clade A isolates, relative to multidrug resistant clade C2 isolates, suggests that resistance is not necessary for clonal success. However, even in the low antibiotic use setting of Norway, resistance to important antimicrobial classes has rapidly been selected for in CC131 clade A isolates. This study shows the importance of genomic surveillance in uncovering the complex ecology underlying multidrug resistance dissemination and competition, which have implications for the design of strategies and interventions to control the spread of high-risk multidrug resistant clones. FUNDING: Trond Mohn Foundation, European Research Council, Marie Skłodowska-Curie Actions, and the Wellcome Trust

Low prevalence of tick-borne encephalitis virus antibodies in Norwegian blood donors

Background: Tick-borne encephalitis (TBE) constitutes a public health concern in Europe. Certain coastal municipalities in southern Norway are considered TBE risk areas and in the last two years, there have been increasing numbers of TBE cases. Since the majority of infections are claimed to be asymptomatic, the aim of the current study was to assess the seroprevalence of antibodies to tick-borne encephalitis virus (TBEV) among unvaccinated adults living in a TBE endemic area in Norway. Methods: One thousand one hundred and twenty-three blood donors living in Vestfold and Telemark county were included and associated sera were analysed for TBEV IgG antibodies. Information regarding tick bites, previous flavivirus exposure and knowledge regarding TBE and TBE prevention were obtained through a questionnaire. Results: Fifty-eight samples were reactive by ELISA, of which 21 (36.2%) were confirmed by a TBEV-specific serum neutralization test. Of the 21 blood donors with neutralizing TBEV antibodies detected, 17 reported previous TBE vaccination.Thus, only four blood donors (0.4%) had TBEV neutralizing antibodies consistent with previously undergone TBEV infection. Regarding TBE awareness, half of the blood donors were familiar with TBE, but only 35% were aware of a preventiveTBE vaccine. Conclusions: Our study indicates low prevalence of subclinical TBEV infections among blood donors living in Vestfold and Telemark county and there is a lack of awareness among general public