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Enterococcus faecium (Efm) is a versatile pathogen, responsible for multidrug-resistant infections, especially in hospitalized immunocompromised patients. Its population structure has been characterized by diverse clades (A1, A2, and B (reclassified as E. lactis (Ela)), adapted to different environments, and distinguished by their resistomes and virulomes. These features only partially explain the predominance of clade A1 strains in nosocomial infections. We investigated in vitro interaction of 50 clinical isolates (clade A1 Efm) against 75 commensal faecal isolates from healthy humans (25 clade A2 Efm and 50 Ela). Only 36% of the commensal isolates inhibited clinical isolates, while 76% of the clinical isolates inhibited commensal isolates. The most apparent overall differences in inhibition patterns were presented between clades. The inhibitory activity was mainly mediated by secreted, proteinaceous, heat-stable compounds, likely indicating an involvement of bacteriocins. A custom-made database targeting 76 Bacillota bacteriocins was used to reveal bacteriocins in the genomes. Our systematic screening of the interactions between nosocomial and commensal Efm and Ela on a large scale suggests that, in a clinical setting, nosocomial strains not only have an advantage over commensal strains due to their possession of AMR genes, virulence factors, and resilience but also inhibit the growth of commensal strains.
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IntroductionNational and regional carbapenemase-producing Enterobacterales (CPE) surveillance is essential to understand the burden of antimicrobial resistance, elucidate outbreaks, and develop infection-control or antimicrobial-treatment recommendations.AimThis study aimed to describe CPE and their epidemiology in Norway from 2015 to 2021.MethodsA 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.ResultsA total of 389 CPE isolates were identified from 332 patients of 63 years 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 1.1 per 100,000 person-years. For CPE-isolates 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 travel-associated cases was observed during the COVID-19 pandemic.ConclusionsThe 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.
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COVID-19 , Infecções por Enterobacteriaceae , Humanos , Masculino , Feminino , Viagem , Epidemiologia Molecular , Pandemias , COVID-19/epidemiologia , Doença Relacionada a Viagens , Proteínas de Bactérias/genética , beta-Lactamases/genética , Escherichia coli , Klebsiella pneumoniae/genética , Infecções por Enterobacteriaceae/epidemiologia , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/uso terapêuticoRESUMO
The global prevalence of infections caused by extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-E) is increasing, and for Escherichia coli, observations indicate that this is partly driven by community-onset cases. The ESBL-E population structure in the community is scarcely described, and data on risk factors for carriage are conflicting. Here, we report the prevalence and population structure of fecal ESBL-producing E. coli and Klebsiella pneumoniae (ESBL-Ec/Kp) in a general adult population, examine risk factors, and compare carriage isolates with contemporary clinical isolates. Fecal samples obtained from 4,999 participants (54% women) ≥40 years in the seventh survey of the population-based Tromsø Study, Norway (2015, 2016), were screened for ESBL-Ec/Kp. In addition, we included 118 ESBL-Ec clinical isolates from the Norwegian surveillance program in 2014. All isolates were whole-genome sequenced. Risk factors associated with carriage were analyzed using multivariable logistic regression. ESBL-Ec gastrointestinal carriage prevalence was 3.3% [95% confidence interval (CI) 2.8%-3.9%, no sex difference] and 0.08% (0.02%-0.20%) for ESBL-Kp. For ESBL-Ec, travel to Asia was the only independent risk factor (adjusted odds ratio 3.46, 95% CI 2.18-5.49). E. coli ST131 was most prevalent in both collections. However, the ST131 proportion was significantly lower in carriage (24%) versus clinical isolates (58%, P < 0.001). Carriage isolates were genetically more diverse with a higher proportion of phylogroup A (26%) than clinical isolates (5%, P < 0.001), indicating that ESBL gene acquisition occurs in a variety of E. coli lineages colonizing the gut. STs commonly related to extraintestinal infections were more frequent in clinical isolates also carrying a higher prevalence of antimicrobial resistance, which could indicate clone-associated pathogenicity.IMPORTANCEESBL-Ec and ESBL-Kp are major pathogens in the global burden of antimicrobial resistance. However, there is a gap in knowledge concerning the bacterial population structure of human ESBL-Ec/Kp carriage isolates in the community. We have examined ESBL-Ec/Kp isolates from a population-based study and compared these to contemporary clinical isolates. The large genetic diversity of carriage isolates indicates frequent ESBL gene acquisition, while those causing invasive infections are more clone dependent and associated with a higher prevalence of antibiotic resistance. The knowledge of factors associated with ESBL carriage helps to identify patients at risk to combat the spread of resistant bacteria within the healthcare system. Particularly, previous travel to Asia stands out as a major risk factor for carriage and should be considered in selecting empirical antibiotic treatment in critically ill patients.