Biology subjects

Hopkins, K. L.

Publications and source records attributed to Hopkins, K. L..

11 recordsLinked to original sources

bioRxiv2026

Global genomic epidemiology of multi-carbapenemase Enterobacterales

Enterobacterales pathogens that encode multiple carbapenemase genes are an emerging public health threat. The genomic and plasmid context of the multi-carbapenemase producers has not yet been explored at scale. We analysed 1501 publicly-available global genomes that encoded two or more genes from the five prevalent carbapenemase families (IMP, KPC, NDM, OXA-48-like, and VIM). We observed 241 distinct allelic combinations, with NDM/OXA-48-like (25.6%), multiple KPC (25.3%), KPC/NDM (18.8%), and multiple NDM (10.9%) being the most common groups. We found that many genomes were part of high-risk lineages (48.0%). Most genomes carried carbapenemase genes on two plasmids (59.2%) or one plasmid (23.5%), and most genomes encoded different carbapenemase families (56.2%) rather than copies of the same allele (36.2%). We observed multiple mechanisms of multi-carbapenemase evolution including plasmid co-integration, convergence with virulence, and generation of novel allele diversity through duplication. Multi-carbapenemase plasmids had more AMR genes that conferred resistance to more AMR classes compared to plasmids encoding a single carbapenemase. The proportion of cross-class combinations (KPC/NDM and NDM/OXA-48-like) increased significantly over time, with NDM-5/OXA-181 (3.3-fold) and NDM-4/OXA-181 (8.9-fold) combinations enriched. These findings provide valuable insights into the genomic features of multi-carbapenemase Enterobacterales to support the development of effective surveillance programmes.

microbiology↗

bioRxiv2026

A panel of genotypically and phenotypically characterised WHO priority Gram-negative bacteria to facilitate antimicrobial and diagnostic development

Background Antimicrobial-resistant Gram-negative bacteria pose a major threat to global health. In the WHO Bacterial Priority Pathogen List (BPPL) 2024, several species were classified as critical or high priority for research and development of new antimicrobial therapeutics and diagnostics. However, access to well-characterised and clinically relevant bacterial isolate panels remains an unmet need for development and validation. Methods We constructed five panels of Gram-negative bacterial isolates, cultured from samples originally referred to the UK Health Security Agency Antimicrobial Resistance and Healthcare-Associated Infections Reference Unit for analysis between 2014 and 2025. For each isolate, antimicrobial susceptibilities were determined against a range of clinically relevant antibiotics, including third-generation cephalosporins, carbapenems, colistin and other last-line antibiotics. WGS was performed on all isolates, and previously described resistance determinants were characterised. Results The five panels consist of 145 isolates and represent 81 sequence types across Escherichia coli (30 isolates), Klebsiella pneumoniae (30 isolates), carbapenem-resistant Acinetobacter baumannii (30 isolates), carbapenem-resistant Pseudomonas aeruginosa (30 isolates), and a mixed panel of other healthcare-associated Enterobacterales species (25 isolates). Panels are highly representative of globally relevant strains, including those currently in circulation and on the WHO BPPL 2024, and of resistance mechanisms of public health importance. Conclusion The panels provide a diverse, comprehensive set of multidrug-resistant Gram-negative bacterial isolates, representative of strains currently in circulation globally. Selected isolates carry a breadth of important resistance mechanisms and are highly relevant to the current epidemiological landscape. The isolates and associated metadata are available to industry, academia, and other laboratories for use in developing novel antimicrobial compounds and diagnostic assays.

microbiology↗

bioRxiv2026

Two IncHI1 megaplasmids in Klebsiella species reveal transposable-element-mediated blaIMP-1 mobilisation

Introduction. Carbapenemase-producing Enterobacterales (CPE) represent a major threat to hospitalised patients worldwide. The dissemination of carbapenemase genes, such as blaIMP, is frequently mediated by mobile genetic elements including plasmids. During a previously described multispecies, healthcare-associated outbreak of blaIMP-positive CPE in North West London, two unusual isolates, IMP47 (Klebsiella grimontii) and IMP76 (K. pneumoniae), recovered in 2019 from routinely collected rectal swabs of inpatients, were predicted to harbour blaIMP-1-carrying IncHI1 megaplasmids. Aims. This study aimed to determine complete genomic sequences of IMP47 and IMP76, resolve the genetic context of blaIMP-1, and assess the conjugative mobility of blaIMP-1-carrying megaplasmids. Methods. Genomic sequences of both isolates were recovered through hybrid assembly of Oxford Nanopore and Illumina sequencing reads. Complete plasmid sequences were characterised to determine replicons, conjugation machinery, and genes encoding resistance to antimicrobials or other stress factors. Integrons and transposable elements (TEs) within flanking regions of blaIMP-1 were resolved through genome annotation and search against public databases. Liquid-mating experiments were performed to assess the mobility of blaIMP-1-carrying plasmids. Results. Completed genome assemblies were generated from both isolates, confirming two blaIMP-1-carrying megaplasmids, pIMP47 (391 kbp) and pIMP76_1 (519 kbp), of the replicon type IncHI1A(pNDM-CIT)/IncHI1B(pNDM-CIT). The blaIMP-1 locus was carried by nearly identical class 1 integrons in both plasmids and a closely related IncHI1 megaplasmid pEB3_IMP1 (361 kbp) previously identified in South West England. Comparative analysis revealed conserved genetic structures linking blaIMP-1 to mercury-resistance genes and TEs Tn6025, TnAs3, IS26, and IS5075, suggesting a history of recombination and potential for TE-mediated mobilisation. Conjugation experiments confirmed transfer of pIMP76_1 into a recipient K. pneumoniae strain, resulting in acquisition of ertapenem resistance, whereas transfer of pIMP47 was not observed under the tested conditions. Conclusion. Two IMP-producing IncHI1 megaplasmids in gut-colonising Klebsiella species revealed TE-mediated blaIMP-1 mobilisation. The co-localisation of blaIMP-1 and metal-resistance genes in both plasmids highlights the potential for co-selection of blaIMP-1 in environments enriched with metal ions. Our findings underscore the importance of longitudinal genomic surveillance of carbapenemase-encoding megaplasmids in healthcare settings.

microbiology↗

bioRxiv2025

Nanopore long-read only genome assembly of clinical Enterobacterales isolates is complete and accurate

Whole bacterial genome sequence reconstruction using Oxford Nanopore Technologies ("Nanopore") long-read only sequencing may offer a lower-cost, higher-throughput alternative for pathogen surveillance to hybrid assembly with recent improvements in Nanopore sequencing accuracy. We evaluated the accuracy, including plasmid reconstruction, of Nanopore long-read only genome assemblies of Enterobacterales. We sequenced 92 genomes from clinical Enterobacterales isolates, collected in England under a national surveillance program, with long-read Nanopore (R10.4.1, Dorado v5.0.0 super-high-accuracy basecalled) and short-read Illumina (NovaSeq) sequencing approaches. Genomes were assembled using three long-read only (Flye; Hybracter long; Autocycler), and three hybrid assemblers (Hybracter hybrid; Unicycler normal; bold). Three polishing modalities (Medaka v2 with subsampled or un-subsampled long-reads; Polypolish + Pypolca with short-reads) were investigated. Autocycler circularised the most chromosomes (87/92 [95%]). Plasmid sequence reconstruction was comparable between all assemblers except Flye, all recovering 90-96% of plasmids, although the ground truth was uncertain. Flye performed worse than other assemblers on almost all metrics. Autocycler + Medaka (un-subsampled long-reads) was the most accurate long-read only assembler/polisher combination, comparable to hybrid assemblies (median 0 [IQR:0-0] SNPs and 0 [IQR:0-1] indels per genome; quality value/Q score, 100 [IQR: 64-100]), with only 4/92 genome sequences having >10 SNPs/indels. Medaka polishing with un-subsampled long-reads resulted in small improvements in indels but not SNPs for both Flye and Autocycler assemblies. Seven-locus MLST, antimicrobial resistance, virulence, and stress gene annotation was equivalent across assembler/polisher combinations. Nanopore long-read only bacterial genome assembly with Autocycler combined with Medaka polishing (using un-subsampled reads) is similarly accurate and possibly more complete than hybrid assemblies, representing a viable alternative for incorporating high-quality genomic data, including plasmids, into Enterobacterales surveillance. Data SummaryNanopore long-reads and Illumina short-reads from the 92 Enterobacterales isolates from this study have been uploaded to ENA (BioProject accession: PRJEB93885). Code for the Nextflow assembly pipeline, downstream analysis scripts, and R statistical analysis scripts are available on GitHub (https://github.com/oxfordmmm/NEKSUS_ont_hybrid_assembly_comparison). The following supplementary data tables are available on FigShare (https://figshare.com/account/home#/projects/253775): O_LIENA Sample accessions and sample metadata (accessions_and_metadata.csv) C_LIO_LISeqkit stats summaries of the Illumina and Nanopore reads (raw_qc_sup.cav) C_LIO_LISummary of assembly contig features (contigs_summary_sup_cleaned.csv) C_LIO_LIPairwise mash distances between contigs (mash_cleaned.csv) C_LIO_LIPlasmids matching across different assemblers compared to the Hybracter (hybrid) and manually-curated reference sets (plasmids_match_hybracter_mash.csv; plasmids_match_manual_mash.csv, respectively) C_LIO_LISeven-locus multi-locus sequence type annotation (mlst_cleaned.csv) C_LIO_LICheckM2 summaries of assemblies (checkm2_cleaned.csv) C_LIO_LINucleotide-level accuracy of assemblies (SNP, Indels, and Quality value compared to short-read mapping; assembly_nucleotide_accuracy_cleaned.csv) C_LIO_LIBakta annotation (bakta_by_contig_cleaned.csv) C_LIO_LIAMRFinderPlus annotations of contigs (amrfinder_plus_cleaned.csv) C_LIO_LIMOB-suite annotation summaries of contigs (mobsuite_cleaned.csv) C_LI Impact StatementNanopore long-reads have historically been too error-prone to use alone for accurate bacterial genome assembly, necessitating additional Illumina short-reads to achieve structurally complete and accurate hybrid genome assemblies for public health surveillance. This increases cost and complexity. Previous studies have shown that recent improvements in Nanopore chemistry (R10.4.1 flowcell) and basecalling (super-high accuracy) allow high-quality long-read only assemblies on a small number of laboratory reference strains. This is the first evaluation, to our knowledge, to assess Nanopore long-read only genome assembly compared with hybrid assembly on a large number of clinical isolates. In addition, this is the first large-scale evaluation of the recently released automated consensus long-read assembly tool, Autocycler. We show that Autocycler long-read only assemblies are more structurally complete for chromosomal sequences, while reconstructing a similar number of plasmids to other long-read and hybrid assemblers. Most long-read polished, Autocycler-assembled genome sequences have 0 errors (median: 0 SNPs/indels) relative to a short-read polished (hybrid) Autocycler assemblies, enabling accurate annotation of key genes.

bioinformatics↗

bioRxiv2025

Genomic and molecular characterisation of a Klebsiella pneumoniae clinical isolate resistant to meropenem-vaborbactam, imipenem-relebactam, and ceftazidime-avibactam

This article reports an unusual Klebsiella pneumoniae clinical isolate, KpMVR1, resistant to meropenem-vaborbactam, imipenem-relebactam, and ceftazidime-avibactam, and investigates the underlying genetic alterations using comparative genomics and molecular experiments. Resistance to carbapenems and third-generation cephalosporins is increasing in K. pneumoniae globally, restricting therapeutic options. The {beta}-lactam/{beta}-lactamase inhibitor combinations are widely used to circumvent {beta}-lactamase-mediated resistance. In 2021, isolate KpMVR1 was recovered from a hospitalised patient in England. Two additional isolates with the same variable-number tandem-repeat profile--KpMVS1, collected from the same patient 42 days before KpMVR1, and KpMVS2, from another patient in the same hospital--were susceptible to meropenem-vaborbactam, imipenem-relebactam, and ceftazidime-avibactam. Illumina and nanopore whole-genome sequencing and hybrid genome assembly were conducted for these three isolates. Annotated genome assemblies were compared to identify genetic variation, and mutagenesis experiments were performed to verify predicted functional alterations. All isolates belonged to a novel clone ST8134 and carried blaKPC-2-like alleles (KpMVR1: blaKPC-157; KpMVS1 and KpMVS2: blaKPC-2) in presumptively conjugative plasmids. ISEc68 caused a frameshift mutation in KpMVR1s ompK36 gene, reducing the meropenem-vaborbactam and imipenem-relebactam susceptibility. KPC-157 demonstrated decreased hydrolysis of imipenem and ceftazidime when compared with KPC-2. KpMVR1 also encoded a disrupted transcriptional repressor MarR and a destabilising mutation in AcrB, a component of the AcrAB-TolC multidrug efflux pump. In conclusion, KpMVR1 harboured complex resistance-associated genetic alterations, with evidence for in vivo emergence of antimicrobial resistance. Our study underlines routine screening for resistant pathogens in vulnerable patients to guide antimicrobial chemotherapy as well as the need to characterise underlying resistance mechanisms to help assess the potential for onward transmission. Data summaryIllumina and nanopore sequencing reads, hybrid genome assemblies, and anonymised metadata of isolates KpMVS1, KpMVR1, and KpMVS2 have been deposited in databases of the National Center for Biotechnology Information (www.ncbi.nlm.nih.gov) under BioProject accession PRJNA1084250, with BioSample accessions SAMN46778009 (KpMVS1), SAMN46778010 (KpMVR1), and SAMN46778011 (KpMVS2). The genome assemblies of these isolates have also been deposited in Pasteur Institutes database for K. pneumoniae species complex (bigsdb.pasteur.fr/klebsiella/) under ids 75608 (KpMVS1), 75609 (KpMVR1), and 75610 (KpMVS2). Impact statementThis is the first blaKPC-positive K. pneumoniae isolate referred to the UKs national reference laboratory with resistance to three last-resort {beta}-lactam/{beta}-lactamase inhibitor combinations meropenem-vaborbactam, imipenem-relebactam, and ceftazidime-avibactam, implicating in vivo emergence of this unusual resistance profile during prolonged antimicrobial chemotherapy. This isolate belonged to a novel clone ST8134 and harboured a plasmid-borne blaKPC-2-like allele blaKPC-157. We identified complex genetic alterations in this isolate: chromosomal large deletions, point mutations, and an ISEc68-induced loss-of-function truncation of the ompK36 porin gene. We determined the impact of KPC-2, KPC-157, and the ompK36 truncation on the susceptibility of K. pneumoniae to meropenem, meropenem-vaborbactam, imipenem, imipenem-relebactam, imipenem-avibactam, aztreonam, aztreonam-avibactam, ceftazidime, ceftazidime-avibactam, and cefiderocol. Our work underscores the need to monitor emerging resistance to beta-lactam/beta-lactamase inhibitor combinations in healthcare and to understand underlying resistance mechanisms for assessing the potential of resistance transmission.

microbiology↗

bioRxiv2024

Plasmid conjugation drives within-patient plasmid diversity

Plasmids are well known vehicles of antimicrobial resistance (AMR) genes dissemination. Through conjugation, plasmid-encoded AMR genes are spread among neighbouring bacteria, irrespective of their strain or even their species. This process is very concerning from a public health perspective, as plasmid-borne AMR gene outbreaks are often not confined to single species or strains and are therefore more difficult to be fully uncovered. At the moment, the impact of plasmid conjugation on within-patient plasmid diversity is not well understood. In this work we will tackle the role of conjugation on within-patient plasmid diversity using a dataset of carbapenemase-producing Enterobacterales (CPEs). The dataset of 256 sequences from 115 patients was sampled across England over 30 months. Each patient has more than one sequence, with at least one sequence carrying an OXA-48 gene, a well-known plasmid-borne carbapenemase-encoding gene. If more than one sequence carries the OXA-48 gene, they are carried on different bacterial hosts. Using a hybrid de novo-on-reference assembly pipeline, we were able to reconstruct the full OXA-48 plasmid from short read sequencing data for 232 of the 256 sequences. Of the 115 patients, 83 (72%) of patients had an identical OXA-48 plasmid in two or more sequences. Only 2 patients carried very different (>200 SNPs) alleles of the OXA-48 plasmid, probably from separate acquisitions. Our study shows that when more than one bacterial host carrying an OXA-48 plasmid is found in a patient, it is most likely that the same plasmid has been shared via conjugation. The event of separate acquisition of different plasmids in different bacterial hosts is highly unlikely in our dataset. Data StatementWe use data provided by Hopkins et al 2022 [16]. The data can be accessed from the National Center for Biotechnology Information (NCBI) and can be found at Bioproject Accession no. PRJNA788733. None of the data used was synthetically generated. Impact StatementConjugative plasmids are well known vessels of horizontal gene transfer, with a prominent role in the spread of antimicrobial resistance genes among different bacterial species or strains. At the epidemiological level, conjugation combined with sequencing a single colony per patient, results in plasmids outbreaks carrying antimicrobial resistance genes being found in different bacterial species and strains in different patients, potentially eluding surveillance protocols based on same bacterium/same resistance scheme. In this study we analyse within-patient plasmid diversity in a dataset with more than one sequence per patient. Only two patients show clear genomic signs of separate plasmids acquisition, while 83 patients share identical plasmids in different bacterial hosts. This points out to a very strong role of plasmid conjugation in shaping within-patient plasmid diversity.

bioinformatics↗

bioRxiv2024

E. coli phylogeny drives co-amoxiclav resistance through variable expression of blaTEM-1

Co-amoxiclav resistance in E. coli is a clinically important phenotype associated with increased mortality. The class A beta-lactamase blaTEM-1 is often carried by co- amoxiclav-resistant pathogens, but exhibits high phenotypic heterogeneity, making genotype-phenotype predictions challenging. We present a curated dataset of n=377 E. coli isolates representing all 8 known phylogroups, where the only acquired beta- lactamase is blaTEM-1. For all isolates, we generate hybrid assemblies and co-amoxiclav MICs, and for a subset (n=67/377), blaTEM-1 qPCR expression data. First, we test whether certain E. coli lineages are intrinsically better or worse at expressing blaTEM-1, for example, due to lineage differences in regulatory systems, which are challenging to directly quantify. Using genotypic features of the isolates (blaTEM-1 promoter variants and copy number), we develop a hierarchical Bayesian model for blaTEM-1 expression that controls for phylogeny. We establish that blaTEM-1 expression intrinsically varies across the phylogeny, with some lineages (e.g. phylogroups B1 and C, ST12) better at expression than others (e.g. phylogroups E and F, ST372). Next, we test whether phylogenetic variation in expression influences the resistance of the isolates. With a second model, we use genotypic features (blaTEM-1 promoter variants, copy number, duplications; ampC promoter variants; efflux pump AcrF presence) to predict isolate MIC, again controlling for phylogeny. Lastly, we use a third model to demonstrate that the phylogenetic influence on blaTEM-1 expression causally drives the variation in co- amoxiclav MIC. This underscores the importance of incorporating phylogeny into genotype-phenotype predictions, and the study of resistance more generally.

microbiology↗

bioRxiv2023

A workflow for the detection of antibiotic residues, measurement of water chemistry and preservation of hospital sink drain samples for metagenomic sequencing

Structured summaryO_ST_ABSBackgroundC_ST_ABSHospital sinks are environmental reservoirs that harbour healthcare-associated (HCA) pathogens. Selective pressures in sink environments, such as antibiotic residues, nutrient waste and hardness ions, may promote antibiotic resistance gene (ARG) exchange between bacteria. However, cheap and accurate sampling methods to characterise these factors are lacking. AimTo validate a workflow to detect antibiotic residues and evaluate water chemistry using dipsticks. Secondarily, to validate boric acid to preserve the taxonomic and ARG ("resistome") composition of sink trap samples for metagenomic sequencing. MethodsAntibiotic residue dipsticks were validated against serial dilutions of ampicillin, doxycycline, sulfamethoxazole and ciprofloxacin, and water chemistry dipsticks against serial dilutions of chemical calibration standards. Sink trap aspirates were used for a "real-world" pilot evaluation of dipsticks. To assess boric acid as a preservative of microbial diversity, the impact of incubation with and without boric acid at [~]22{degrees}C on metagenomic sequencing outputs was evaluated at Day 2 and Day 5 compared with baseline (Day 0). FindingsThe limits of detection for each antibiotic were: 3{micro}g/L (ampicillin), 10{micro}g/L (doxycycline), 20{micro}g/L (sulfamethoxazole) and 8{micro}g/L (ciprofloxacin). The best performing water chemistry dipstick correctly characterised 34/40 (85%) standards in a concentration-dependent manner. One trap sample tested positive for the presence of tetracyclines and sulfonamides. Taxonomic and resistome composition were largely maintained after storage with boric acid at [~]22{degrees}C for up to five days. ConclusionsDipsticks can be used to detect antibiotic residues and characterise water chemistry in sink trap samples. Boric acid was an effective preservative of trap sample composition, representing a low-cost alternative to cold-chain transport.

microbiology↗

bioRxiv2020

Emergence of optrA-mediated linezolid resistance in multiple lineages and plasmids of Enterococcus faecalis revealed by long read sequencing

ObjectivesTo characterise the genetic environment of optrA in linezolid-resistant Enterococcus faecalis isolates from Scotland. MethodsLinezolid-resistant E. faecalis were identified in three Scottish Health Boards and confirmed to carry the optrA gene at the national reference laboratory. WGS was performed with short read (Illumina MiSeq) and long read (Oxford Nanopore MinION) technologies to generate complete genome assemblies. Illumina reads for 94 E. faecalis bloodstream isolates were used to place the optrA-positive isolates in a larger UK phylogeny. ResultsSix optrA-positive linezolid-resistant E. faecalis were isolated from urogenital samples in three Scottish Health Boards (2014-2017). No epidemiological links were identified between the patients, four were community-based, and only one had recent linezolid exposure. Reference-based mapping confirmed the isolates were genetically distinct (>13,900 core SNPs). optrA was located on a plasmid in each isolate and these plasmids showed limited nucleotide similarity. There was variable presence of transposable elements surrounding optrA, (including IS1216, IS3, and Tn3) and not always as a recognisable gene cassette. OptrA amino acid sequences were also divergent, resulting in four protein variants differing in 1-20 residues. One isolate belonged to ST16 and clustered with three other isolates in the UK collection (76-182 SNPs), otherwise the optrA-positive isolates were genetically distinct from the bloodstream isolates (>6,000 SNPs). ConclusionsWe report multiple variants of the linezolid resistance gene optrA in diverse E. faecalis strain and plasmid backgrounds, suggesting multiple introductions of the gene into the E. faecalis population and selection driving recent emergence.

microbiology↗

bioRxiv2019

Genomic epidemiology of a complex, multi-species plasmid-borne blaKPC carbapenemase outbreak in Enterobacterales in the UK, 2009-2014

Carbapenem resistance in Enterobacterales is a public health threat. Klebsiella pneumoniae carbapenemase (encoded by alleles of the blaKPC family) is one of the commonest transmissible carbapenem resistance mechanisms worldwide. The dissemination of blaKPC has historically been associated with distinct K. pneumoniae lineages (clonal group 258 [CG258]), a particular plasmid family (pKpQIL), and a composite transposon (Tn4401). In the UK, blaKPC has caused a large-scale, persistent outbreak focused on hospitals in North-West England. This outbreak has evolved to be polyclonal and poly-species, but the genetic mechanisms underpinning this evolution have not been elucidated in detail; this study used short-read whole genome sequencing of 604 blaKPC-positive isolates (Illumina) and long-read assembly (PacBio)/polishing (Illumina) of 21 isolates for characterisation. We observed the dissemination of blaKPC (predominantly blaKPC-2; 573/604 [95%] isolates) across eight species and more than 100 known sequence types. Although there was some variation at the transposon level (mostly Tn4401a, 584/604 (97%) isolates; predominantly with ATTGA-ATTGA target site duplications, 465/604 [77%] isolates), blaKPC spread appears to have been supported by highly fluid, modular exchange of larger genetic segments amongst plasmid populations dominated by IncFIB (580/604 isolates), IncFII (545/604 isolates) and IncR replicons (252/604 isolates). The subset of reconstructed plasmid sequences also highlighted modular exchange amongst non-blaKPC and blaKPC plasmids, and the common presence of multiple replicons within blaKPC plasmid structures (>60%). The substantial genomic plasticity observed has important implications for our understanding of the epidemiology of transmissible carbapenem resistance in Enterobacterales, for the implementation of adequate surveillance approaches, and for control.\n\nIMPORTANCEAntimicrobial resistance is a major threat to the management of infections, and resistance to carbapenems, one of the \"last line\" antibiotics available for managing drug-resistant infections, is a significant problem. This study used large-scale whole genome sequencing over a five-year period in the UK to highlight the complexity of genetic structures facilitating the spread of an important carbapenem resistance gene (blaKPC) amongst a number of bacterial species that cause disease in humans. In contrast to a recent pan-European study from 2012-2013(1), which demonstrated the major role of spread of clonal blaKPC-Klebsiella pneumoniae lineages in continental Europe, our study highlights the substantial plasticity in genetic mechanisms underpinning the dissemination of blaKPC. This genetic flux has important implications for: the surveillance of drug resistance (i.e. making surveillance more difficult); detection of outbreaks and tracking hospital transmission; generalizability of surveillance findings over time and for different regions; and for the implementation and evaluation of control interventions.

genomics↗

bioRxiv2019

When do big problems far away become smaller than the problems closer to home: Lessons for antimicrobial resistance from Father Ted

Infection prevention and control strategies aimed at reducing the occurrence of Carbapenemase-Producing Enterobacteriaceae (CPE) and other antimicrobial-resistant organisms often include advice about screening patients coming from hospitals with a known resistance problem, to prevent introductions into new hospitals by shared patients. We argue that, despite being an efficient method of identifying cases, admission screening for introduction prevention is only effective if the absolute number of imported cases from other hospitals outnumbers the cases coming from the hospitals own patient population, and therefore is only a feasible control strategy during the start of an epidemic. When determining whether import screening is still advisable, we therefore need to be continuously reminded of how Father Ted so eloquently summarised the principles of perspective: "These are small, but the ones out there are far away".

epidemiology↗