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Background Multiresistant organisms (MROs) pose a critical threat to public health. Population-based programs for control of MROs such as carbapenemase-producing Enterobacterales (CPE) have emerged and evaluation is needed. We assessed the feasibility and impact of a statewide CPE surveillance and response program deployed across Victoria, Australia (population 6.5 million). Methods A prospective multimodal intervention including active screening, carrier isolation, centralized case investigation, and comparative pathogen genomics was implemented. We analyzed trends in CPE incidence and clinical presentation, risk factors, and local transmission over the program's first 3 years (2016–2018). Results CPE case ascertainment increased over the study period to 1.42 cases/100 000 population, linked to increased screening without a concomitant rise in active clinical infections (0.45–0.60 infections/100 000 population, P  = .640). KPC-2 infection decreased from 0.29 infections/100 000 population prior to intervention to 0.03 infections/100 000 population in 2018 (P  = .003). Comprehensive case investigation identified instances of overseas community acquisition. Median time between isolate referral and genomic and epidemiological assessment for local transmission was 11 days (IQR, 9–14). Prospective surveillance identified numerous small transmission networks (median, 2; range, 1–19 cases), predominantly IMP and KPC, with median pairwise distance of 8 (IQR, 4–13) single nucleotide polymorphisms; low diversity between clusters of the same sequence type suggested genomic cluster definitions alone are insufficient for targeted response. Conclusions We demonstrate the value of centralized CPE control programs to increase case ascertainment, resolve risk factors, and identify local transmission through prospective genomic and epidemiological surveillance; methodologies are transferable to low-prevalence settings and MROs globally. [ABSTRACT FROM AUTHOR]

Interpreting the phenotypes of bla SHV alleles in Klebsiella pneumoniae genomes is complex. Whilst all strains are expected to carry a chromosomal copy conferring resistance to ampicillin, they may also carry mutations in chromosomal bla SHV alleles or additional plasmid-borne bla SHV alleles that have extended-spectrum β-lactamase (ESBL) activity and/or β-lactamase inhibitor (BLI) resistance activity. In addition, the role of individual mutations/a changes is not completely documented or understood. This has led to confusion in the literature and in antimicrobial resistance (AMR) gene databases [e.g. the National Center for Biotechnology Information (NCBI) Reference Gene Catalog and the β-lactamase database (BLDB)] over the specific functionality of individual sulfhydryl variable (SHV) protein variants. Therefore, the identification of ESBL-producing strains from K. pneumoniae genome data is complicated. Here, we reviewed the experimental evidence for the expansion of SHV enzyme function associated with specific aa substitutions. We then systematically assigned SHV alleles to functional classes (WT, ESBL and BLI resistant) based on the presence of these mutations. This resulted in the re-classification of 37 SHV alleles compared with the current assignments in the NCBI's Reference Gene Catalog and/or BLDB (21 to WT, 12 to ESBL and 4 to BLI resistant). Phylogenetic and comparative genomic analyses support that (i) SHV-1 (encoded by bla SHV-1 ) is the ancestral chromosomal variant, (ii) ESBL- and BLI-resistant variants have evolved multiple times through parallel substitution mutations, (iii) ESBL variants are mostly mobilized to plasmids and (iv) BLI-resistant variants mostly result from mutations in chromosomal bla SHV . We used matched genome-phenotype data from the KlebNET-GSP AMR Genotype-Phenotype Group to identify 3999 K . pneumoniae isolates carrying one or more bla SHV alleles but no other acquired β-lactamases to assess genotype-phenotype relationships for bla SHV . This collection includes human, animal and environmental isolates collected between 2001 and 2021 from 24 countries. Our analysis supports that mutations at Ambler sites 238 and 179 confer ESBL activity, whilst most omega-loop substitutions do not. Our data also provide support for the WT assignment of 67 protein variants, including 8 that were noted in public databases as ESBL. These eight variants were reclassified as WT because they lack ESBL-associated mutations, and our phenotype data support susceptibility to third-generation cephalosporins (SHV-27, SHV-38, SHV-40, SHV-41, SHV-42, SHV-65, SHV-164 and SHV-187). The approach and results outlined here have been implemented in Kleborate v2.4.1 (a software tool for genotyping K. pneumoniae ), whereby known and novel bla SHV alleles are classified based on causative mutations. Kleborate v2.4.1 was updated to include ten novel protein variants from the KlebNET-GSP dataset and all alleles in public databases as of November 2023. This study demonstrates the power of sharing AMR phenotypes alongside genome data to improve the understanding of resistance mechanisms.

Background: Common infections of the skin such as impetigo and scabies represent a large burden of disease globally, being particularly prevalent in tropical and resource-limited settings. Efforts to address these infections through mass drug administrations have recently been shown as efficacious and safe. In Samoa, a Pacific Island nation, there is a marked lack of epidemiological data for these neglected tropical diseases, or appreciation of their drivers in this setting., Methods: An observational, cross-sectional survey of children aged between 4 and 15 years attending primary schools in rural areas of Upolu Island, Samoa was carried out to assess the prevalence of impetigo and scabies in schoolchildren residing in rural Samoa, integrated with descriptive epidemiological and microbial genomic data. A phylogenetic assessment of local Staphylococcus aureus isolated from Samoan schoolchildren was performed to estimate putative community transmission., Findings: In this survey, the prevalence of impetigo observed in Samoan schoolchildren was one of the highest described globally (57•1%, 95% CI [53•8-60•5%], 476/833). Associations between active impetigo and age and gender were noted, with younger children and males more commonly affected (aOR2•8 [1•8-4•7]and aOR1•8 [1•3-2•5], respectively). The prevalence of scabies was similar to that seen in other South Pacific island countries (14•4%, 95% CI [12•2-17•0%], 120/833). Transmission of S. aureus was predicted, primarily between those children attending the same school. Carriage of S. pyogenes was notably low, with pharyngeal carriage observed in less than 2% of schoolchildren, consistent with earlier studies from Samoa., Interpretation: This study describes a considerable burden of disease attributed to impetigo and scabies in Samoa. These findings will be valuable in addressing the public health challenge posed by these conditions, providing baseline prevalence data and highlighting practical strategies to reduce transmission of relevant microbes and parasites in this setting., Tala Tomua: O a'afiaga o le pa'u i fa'ama'i o le po'u (impetigo) ma le utu o le pa'u (scabies), ua tele naua le fanau ua maua ai i le pasefika, ma le lalolagi atoa. O fuafuaga vaai mamao ma polokalame e fofoina ai nei faafitauli, e aofia ai le inumaga o fualaau e tapeina ai nei fa'ama'i, ua aliali mai ai e mafai ona faatamaia nei fa'ama'i. E le o tele ni tusitusiga ma faamaumauga i totonu o Samoa, pe ta'atele nei fa'amai o le pa'u pe leai. Ona o le le faatauaina o nei fa'ama'i, e le o iloa fo'i ni mafuaga ma nisi tulaga e faateleina ai nei fa'ama'i o le pa'u i Samoa., Faatinoina O Le Suesuega: O le suesuega faasaenisi i le fanau aoga i le va o le 4 ma le 15 tausaga o loo ao'oga i le tulaga lua i nisi o nu'u i tua i Upolu, na faatinoina ai suesuega lea, ia suesueina ai le aotelega ma fainumera o le fanau ua maua i fa'ama'I o le po'u (impetigo) ma le utu o le pa'u (scabies). O lenei foi suesuega, na fia iloa ai fo'i po'o a ituaiga siama eseese o loo maua i luga o pa'u ma tino o le fanau aoga, ina ia iloa ai foi auala ua pipisi ai nei siama mai le isi tamaitiiti i le isi, ona mafua ai lea o nei fa'ama'i o le pa'u., Tanuuga O Le Suesuega: Ua faailoa mai i le suesuega, le ta'atele o le fa'ama'i o le po'u (impetigo) ua maua ai le fanau aoga (57%), i aoga na faia ai le suesuega. O se fainumera ua maualuga tele i le lalolagi atoa. E toatele atu nisi o le fanau laiti (younger) ma tama (male) e maua i le po'u nai lo isi tamaiti. O le fainumera o le utu o le pa'u (scabies) (14·4%) e tai tutusa lava ma isi motu o le Pasefika. O le feaveaina o le siama faapitoa (staph aureus) ua tupu lea i le fanau ua ao'oga i le aoga e tasi. E le toatele foi nisi o le fanau (2%) na maua i le siama faapitoa o le fa'ai (strep pyogenes) e ona mafua ai le fiva rumatika. O lenei fainumera ua tai tutusa ma suesuega faasaenisi na fai muamua i Samoa., Aotelega: O le aotelega la o lenei suesuega faasaenisi, ua faailoaina mai ai le tele naua o le fa'ama'i o le pa'u, o po'u (impetigo) ma le utu o le pa'u (scabies) i Samoa nei. O nei foi suesuega o le a aoga tele ini polokalame ma ni fuafuaga mamao e fa'afoisia ai nei faafitauli i le soifua maloloina o le fanau i Samoa. O le a avea foi nei fainumera e faamaumauina mo le silafia e le atunuu ma le soifua maloloina, le ta'atele o nei fa'amai o le pa'u, mo le tapenaina o ni fofo talafeagai ise taimi o i luma, ina ia faaitiitina ai le pipisi o nei siami i fanau ao'oga i Samoa., Competing Interests: The authors have no known conflicts of interest to declare., (© 2020 The Author(s). Published by Elsevier Ltd.)