68 results found
Snoek L, Karampatsas K, Bijlsma MW, et al., 2023, Meeting report: Towards better risk stratification, prevention and therapy of invasive GBS disease, ESPID research meeting May 2022., Vaccine
The European Society of Pediatric Infectious Diseases (ESPID) hosted the third Group B Streptococcus (GBS) Research Session in Athens on 11th May 2022, providing researchers and clinicians from around the world an opportunity to share and discuss recent advances in GBS pathophysiology, molecular and genetic epidemiology and how these new insights can help in improving prevention and control of early- and late-onset GBS disease. The meeting provided a state-of-the-art overview of the existing GBS prevention strategies and their limitations, and an opportunity to share the latest research findings. The first presentation provided an overview of current GBS prevention and treatment strategies. In the second presentation, the genomic and antimicrobial resistance profiles of invasive and colonizing GBS strains were presented. The third presentation explained the association of intrapartum antibiotic prophylaxis (IAP) with the development of late-onset disease (LOD) and the interplay of host innate immunity and GBS. The fourth presentation evaluated the role of genomics in understanding horizontal GBS transmission. The fifth presentation focused on the zoonotic links for certain GBS lineages and the last presentation described the protective role of breastmilk. Talks were followed with interactive discussions and concluded with recommendations on what is needed to further GBS clinical research; these included: (i) the development of better risk stratification methods by combining GBS virulence factors, serological biomarkers and clinical risk factors; (ii) further studies on the interplay of perinatal antimicrobials, disturbances in the development of host immunity and late-onset GBS disease; (iii) routine submission of GBS isolates to reference laboratories to help in detecting potential clusters by using genomic sequencing; (iv) collaboration in animal and human GBS studies to detect and prevent the emergence of new pathogenic sequence types; and (v) harnessing the plet
Wan Y, Ganner M, Mumin Z, et al., 2023, Whole-genome sequencing reveals widespread presence of Staphylococcus capitis NRCS-A clone in neonatal units across the United Kingdom, Journal of Infection, Vol: 87, Pages: 210-219, ISSN: 0163-4453
OBJECTIVE: Increased incidence of neonatal Staphylococcus capitis bacteraemia in summer 2020, London, raised suspicion of widespread multidrug-resistant clone NRCS-A. We set out to investigate the molecular epidemiology of this clone in neonatal units (NNUs) across the UK. METHODS: We conducted whole-genome sequencing (WGS) on presumptive S. capitis NRCS-A isolates collected from infants admitted to NNUs and from environmental sampling in two distinct NNUs in 2021. Previously published S. capitis genomes were added for comparison. Genetic clusters of NRCS-A isolates were defined based on core-genome single-nucleotide polymorphisms. RESULTS: We analysed WGS data of 838S. capitis isolates and identified 750 NRCS-A isolates. We discovered a possible UK-specific NRCS-A lineage consisting of 611 isolates collected between 2005-2021. We determined 28 genetic clusters of NRCS-A isolates, which covered all geographical regions in the UK, and isolates of 19 genetic clusters were found in ≥2 regions, suggesting inter-regional spread. Within the NRCS-A clone, strong genetic relatedness was identified between contemporary clinical and incubator-associated fomite isolates and between clinical isolates associated with inter-hospital infant transfer. CONCLUSIONS: This WGS-based study confirms the dispersion of S. capitis NRCS-A clone amongst NNUs across the UK and urges research on improving clinical management of neonatal S. capitis infection.
Wan Y, Sabnis A, Mumin Z, et al., 2023, IS1-related large-scale deletion of chromosomal regions harbouring the oxygen-insensitive nitroreductase gene nfsB causes nitrofurantoin heteroresistance in Escherichia coli, Microbial Genomics, Vol: 9, Pages: 1-11, ISSN: 2057-5858
Nitrofurantoin is a broad-spectrum first-line antimicrobial used for managing uncomplicated urinary tract infection (UTI). Loss-of-function mutations in chromosomal genes nfsA, nfsB and ribE of Escherichia coli are known to reduce nitrofurantoin susceptibility. Here, we report the discovery of nitrofurantoin heteroresistance in E. coli clinical isolates and a novel genetic mechanism associated with this phenomenon. Subpopulations with lower nitrofurantoin susceptibility than major populations (hereafter, nitrofurantoin-resistant subpopulations) in two E. coli blood isolates (previously whole-genome sequenced) were identified using population analysis profiling. Each isolate was known to have a loss-of-function mutation in nfsA. From each isolate, four nitrofurantoin-resistant isolates were derived at a nitrofurantoin concentration of 32 mg l-1, and a comparator isolate was obtained without any nitrofurantoin exposure. Genomes of derived isolates were sequenced on Illumina and Nanopore MinION systems. Genetic variation between isolates was determined based on genome assemblies and read mapping. Nitrofurantoin minimum inhibitory concentrations (MICs) of both blood isolates were 64 mg l-1, with MICs of major nitrofurantoin-susceptible populations varying from 4 to 8 mg l-1. Two to 99 c.f.u. per million demonstrated growth at the nitrofurantoin concentration of 32 mg l-1, which is distinct from that of a homogeneously susceptible or resistant isolate. Derived nitrofurantoin-resistant isolates had 11-66 kb deletions in chromosomal regions harbouring nfsB, and all deletions were immediately adjacent to IS1-family insertion sequences. Our findings demonstrate that the IS1-associated large-scale genetic deletion is a hitherto unrecognized mechanism of nitrofurantoin heteroresistance and could compromise UTI management. Further, frequencies of resistant subpopulations from nitrofurantoin-heteroresistant isolates may cha
Boonyasiri A, Brinkac LM, Jauneikaite E, et al., 2023, Characteristics and genomic epidemiology of colistin-resistant Enterobacterales from farmers, swine, and hospitalized patients in Thailand, 2014-2017, BMC Infectious Diseases, Vol: 23, Pages: 1-14, ISSN: 1471-2334
BACKGROUND: Colistin is one of the last resort therapeutic options for treating carbapenemase-producing Enterobacterales, which are resistant to a broad range of beta-lactam antibiotics. However, the increased use of colistin in clinical and livestock farming settings in Thailand and China, has led to the inevitable emergence of colistin resistance. To better understand the rise of colistin-resistant strains in each of these settings, we characterized colistin-resistant Enterobacterales isolated from farmers, swine, and hospitalized patients in Thailand. METHODS: Enterobacterales were isolated from 149 stool samples or rectal swabs collected from farmers, pigs, and hospitalized patients in Thailand between November 2014-December 2017. Confirmed colistin-resistant isolates were sequenced. Genomic analyses included species identification, multilocus sequence typing, and detection of antimicrobial resistance determinants and plasmids. RESULTS: The overall colistin-resistant Enterobacterales colonization rate was 26.2% (n = 39/149). The plasmid-mediated colistin-resistance gene (mcr) was detected in all 25 Escherichia coli isolates and 9 of 14 (64.3%) Klebsiella spp. isolates. Five novel mcr allelic variants were also identified: mcr-2.3, mcr-3.21, mcr-3.22, mcr-3.23, and mcr-3.24, that were only detected in E. coli and Klebsiella spp. isolates from farmed pigs. CONCLUSION: Our data confirmed the presence of colistin-resistance genes in combination with extended spectrum beta-lactamase genes in bacterial isolates from farmers, swine, and patients in Thailand. Differences between the colistin-resistance mechanisms of Escherichia coli and Klebsiella pneumoniae in hospitalized patients were observed, as expected. Additionally, we identified mobile colistin-resistance mcr-1.1 genes from swine and patient isolates belonging to plasmids of the same incompatibility group. This supported the possibility that horizontal transmission of bacterial strains or plasmid-
Yip AYG, King OG, Omelchenko O, et al., 2023, Antibiotics promote intestinal growth of carbapenem-resistant Enterobacteriaceae by enriching nutrients and depleting microbial metabolites, Nature Communications, Vol: 14, Pages: 1-20, ISSN: 2041-1723
The intestine is the primary colonisation site for carbapenem-resistant Enterobacteriaceae (CRE) and serves as a reservoir of CRE that cause invasive infections (e.g. bloodstream infections). Broad-spectrum antibiotics disrupt colonisation resistance mediated by the gut microbiota, promoting the expansion of CRE within the intestine. Here, we show that antibiotic-induced reduction of gut microbial populations leads to an enrichment of nutrients and depletion of inhibitory metabolites, which enhances CRE growth. Antibiotics decrease the abundance of gut commensals (including Bifidobacteriaceae and Bacteroidales) in ex vivo cultures of human faecal microbiota; this is accompanied by depletion of microbial metabolites and enrichment of nutrients. We measure the nutrient utilisation abilities, nutrient preferences, and metabolite inhibition susceptibilities of several CRE strains. We find that CRE can use the nutrients (enriched after antibiotic treatment) as carbon and nitrogen sources for growth. These nutrients also increase in faeces from antibiotic-treated mice and decrease following intestinal colonisation with carbapenem-resistant Escherichia coli. Furthermore, certain microbial metabolites (depleted upon antibiotic treatment) inhibit CRE growth. Our results show that killing gut commensals with antibiotics facilitates CRE colonisation by enriching nutrients and depleting inhibitory microbial metabolites.
Chindelevitch L, van Dongen M, Graz H, et al., 2023, Ten simple rules for the sharing of bacterial genotype-Phenotype data on antimicrobial resistance., PLoS Comput Biol, Vol: 19
The increasing availability of high-throughput sequencing (frequently termed next-generation sequencing (NGS)) data has created opportunities to gain deeper insights into the mechanisms of a number of diseases and is already impacting many areas of medicine and public health. The area of infectious diseases stands somewhat apart from other human diseases insofar as the relevant genomic data comes from the microbes rather than their human hosts. A particular concern about the threat of antimicrobial resistance (AMR) has driven the collection and reporting of large-scale datasets containing information from microbial genomes together with antimicrobial susceptibility test (AST) results. Unfortunately, the lack of clear standards or guiding principles for the reporting of such data is hampering the field's advancement. We therefore present our recommendations for the publication and sharing of genotype and phenotype data on AMR, in the form of 10 simple rules. The adoption of these recommendations will enhance AMR data interoperability and help enable its large-scale analyses using computational biology tools, including mathematical modelling and machine learning. We hope that these rules can shed light on often overlooked but nonetheless very necessary aspects of AMR data sharing and enhance the field's ability to address the problems of understanding AMR mechanisms, tracking their emergence and spread in populations, and predicting microbial susceptibility to antimicrobials for diagnostic purposes.
Zhi X, Li HK, Li H, et al., 2023, Emerging invasive group A Streptococcus M1UK lineage detected by allele-specific PCR, England, 2020, Emerging Infectious Diseases, Vol: 29, Pages: 1007-1010, ISSN: 1080-6040
Increasing reports of invasive Streptococcus pyogenes infections mandate surveillance for toxigenic lineage M1UK. An allele-specific PCR was developed to distinguish M1UK from other emm1 strains. The M1UK lineage represented 91% of invasive emm1 isolates in England in 2020. Allele-specific PCR will permit surveillance for M1UK without need for genome sequencing.
Li H-K, Zhi X, Vieira A, et al., 2023, Characterisation of emergent toxigenic M1UK Streptococcus pyogenes and associated sublineages, Microbial Genomics, Vol: 9, Pages: 1-15, ISSN: 2057-5858
Streptococcus pyogenes genotype emm1 is a successful, globally distributed epidemic clone that is regarded as inherently virulent. An emm1 sublineage, M1UK, that produces increased levels of SpeA toxin was associated with increased scarlet fever and invasive infections in England in 2015/2016. Defined by 27 SNPs in the core genome, M1UK is now dominant in England. To more fully characterize M1UK, we undertook comparative transcriptomic and proteomic analyses of M1UK and contemporary non-M1UKemm1 strains (M1global). Just seven genes were differentially expressed by M1UK compared with contemporary M1global strains. In addition to speA, five genes in the operon that includes glycerol dehydrogenase were upregulated in M1UK (gldA, mipB/talC, pflD, and phosphotransferase system IIC and IIB components), while aquaporin (glpF2) was downregulated. M1UK strains have a stop codon in gldA. Deletion of gldA in M1global abrogated glycerol dehydrogenase activity, and recapitulated upregulation of gene expression within the operon that includes gldA, consistent with a feedback effect. Phylogenetic analysis identified two intermediate emm1 sublineages in England comprising 13/27 (M113SNPs) and 23/27 SNPs (M123SNPs), respectively, that had failed to expand in the population. Proteomic analysis of invasive strains from the four phylogenetic emm1 groups highlighted sublineage-specific changes in carbohydrate metabolism, protein synthesis and protein processing; upregulation of SpeA was not observed in chemically defined medium. In rich broth, however, expression of SpeA was upregulated ~10-fold in both M123SNPs and M1UK sublineages, compared with M113SNPs and M1global. We conclude that stepwise accumulation of SNPs led to the emergence of M1UK. While increased expression of SpeA is a key indicator of M1UK and undoubtedly important, M1UK strains have outcompeted M123SNPs and other emm types that produce similar or more superantigen toxin. We speculate that an accumulation of adaptive SN
Khan UB, Portal EAR, Sands K, et al., 2023, Genomic analysis reveals new integrative conjugal elements and transposons in gbs conferring antimicrobial resistance, Antibiotics, Vol: 12, Pages: 1-16, ISSN: 2079-6382
Streptococcus agalactiae or group B streptococcus (GBS) is a leading cause of neonatal sepsis and increasingly found as an invasive pathogen in older patient populations. Beta-lactam antibiotics remain the most effective therapeutic with resistance rarely reported, while the majority of GBS isolates carry the tetracycline resistance gene tet(M) in fixed genomic positions amongst five predominant clonal clades. In the UK, GBS resistance to clindamycin and erythromycin has increased from 3% in 1991 to 11.9% (clindamycin) and 20.2% (erythromycin), as reported in this study. Here, a systematic investigation of antimicrobial resistance genomic content sought to fully characterise the associated mobile genetic elements within phenotypically resistant GBS isolates from 193 invasive and non-invasive infections of UK adult patients collected during 2014 and 2015. Resistance to erythromycin and clindamycin was mediated by erm(A) (16/193, 8.2%), erm(B) (16/193, 8.2%), mef(A)/msr(D) (10/193, 5.1%), lsa(C) (3/193, 1.5%), lnu(C) (1/193, 0.5%), and erm(T) (1/193, 0.5%) genes. The integrative conjugative elements (ICEs) carrying these genes were occasionally found in combination with high gentamicin resistance mediating genes aac(6′)-aph(2″), aminoglycoside resistance genes (ant(6-Ia), aph(3′-III), and/or aad(E)), alternative tetracycline resistance genes (tet(O) and tet(S)), and/or chloramphenicol resistance gene cat(Q), mediating resistance to multiple classes of antibiotics. This study provides evidence of the retention of previously reported ICESag37 (n = 4), ICESag236 (n = 2), and ICESpy009 (n = 3), as well as the definition of sixteen novel ICEs and three novel transposons within the GBS lineage, with no evidence of horizontal transfer.
Harvey EJ, Ashiru-Oredope D, Hill LF, et al., 2023, Need for standardized vancomycin dosing for coagulase-negative staphylococci in hospitalized infants., Clin Microbiol Infect, Vol: 29, Pages: 10-12
Vieira A, Soo VWC, Li HK, et al., 2023, Tricontinental detection of Streptococcus pyogenes M1<sub>UK</sub>: A call for wider research and active surveillance
<h4>Summary</h4> The Streptococcus pyogenes M1 UK lineage, characterised by an intrinsic ability to express SpeA toxin and defined by 27 single nucleotide polymorphisms in the core genome, dominates the population of emm 1 S. pyogenes isolates in England. The lineage has been identified elsewhere in Europe, North America, and, most recently, Australia. SpeA however may not be the sole deterministic factor underlying success of the M1 UK lineage. Production of SpeA by strains belonging to an intermediate emm 1 sublineage, M1 23SNP , is indistinguishable from M1 UK strains. Despite this, in England at least, M1 UK has outcompeted strains from the M1 23SNP sublineage. We infer that the fitness of M1 UK resides in additional properties that confer an advantage to S. pyogenes , underlining a need for further research. A single nucleotide polymorphism (SNP) in the ssrA leader sequence upstream of speA is one of a limited number of SNPs that distinguish intermediate sublineages that differ in SpeA production. Introduction of the ssrA SNP into representative isolates of the widely disseminated M1 global clone and the intermediate M1 13SNP lineage (that cannot otherwise produce readily-detectable SpeA in culture) resulted in SpeA expression, confirming the importance of the ssrA SNP to SpeA phenotype. However, RNAseq analysis of clinical strains showed that presence of the SNP was not invariably linked to read-through from the ssrA leader sequence or SpeA expression. Literature review suggests that read through and speA mRNA transcript length may be impacted by the two component regulator CovRS, pointing to a complex regulatory network interaction between the bacterial chromosome and phage-encoded superantigens.
Li HK, Zhi X, Vieira A, et al., 2022, Characterisation of emergent toxigenic M1<sub>UK</sub><i>Streptococcus pyogenes</i>and associated sublineages
<jats:title>Abstract</jats:title><jats:p><jats:italic>Emm</jats:italic>1<jats:italic>Streptococcus pyogenes</jats:italic>is a successful, globally-distributed epidemic clone that is regarded as inherently invasive. An<jats:italic>emm</jats:italic>1 sublineage, M1<jats:sub>UK</jats:sub>, that expresses increased SpeA toxin, was associated with increased scarlet fever and invasive infections in England in 2015/2016. Defined by 27 SNPs in the core genome, M1<jats:sub>UK</jats:sub>is now dominant in England. To more fully characterise M1<jats:sub>UK</jats:sub>, we undertook comparative transcriptomic and proteomic analyses of M1<jats:sub>UK</jats:sub>and contemporary non-M1<jats:sub>UK</jats:sub><jats:italic>emm</jats:italic>1 strains (M1<jats:sub>global</jats:sub>).</jats:p><jats:p>Just seven genes were differentially expressed by M1<jats:sub>UK</jats:sub>compared with contemporary M1<jats:sub>global</jats:sub>strains. In addition to speA, five genes in the operon that includes glycerol dehydrogenase were upregulated in M1<jats:sub>UK</jats:sub>(gldA, mipB/talC, pflD, and pts system IIC and IIB components), while aquaporin (glpF2) was downregulated. M1<jats:sub>UK</jats:sub>strains have a stop codon in gldA. Deletion of the gldA gene in M1<jats:sub>global</jats:sub>abrogated glycerol dehydrogenase activity, and recapitulated upregulation of gene expression within the operon that includes gldA, consistent with a feedback effect.</jats:p><jats:p>Phylogenetic analysis identified two intermediate<jats:italic>emm</jats:italic>1 sublineages in England comprising 13/27 (M1<jats:sub>13SNPs</jats:sub>) and 23/27 SNPs (M1<jats:sub>23SNPs</jats:sub>) respectively, that had failed to expand in the population. Proteomic analysis
<jats:title>Summary</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>An increasing burden of invasive group A streptococcal infections is reported in multiple countries, notably England, where scarlet fever cases are also abundant. In England, increased scarlet fever and invasive infections have been associated with emergence of a sublineage of<jats:italic>emm</jats:italic>1<jats:italic>Streptococcus pyogenes</jats:italic>that expresses increased SpeA scarlet fever erythrogenic toxin. Wider surveillance for toxigenic<jats:italic>Streptococcus pyogenes</jats:italic>lineage M1<jats:sub>UK</jats:sub>is much needed however, to date, lineage assignment has required genome sequencing limiting surveillance to those centres with access to such facilities.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>To circumvent the requirement for genome sequencing, an allele-specific PCR was developed to distinguish M1<jats:sub>UK</jats:sub>from other<jats:italic>emm</jats:italic>1 strains. Additional PCR assays were developed to distinguish M1<jats:sub>UK</jats:sub>from two intermediate lineages that were detected previously. The assay was evaluated using DNA from genome-sequenced upper respiratory tract<jats:italic>emm</jats:italic>1<jats:italic>S. pyogenes</jats:italic>strains and a further set of 16 genome-sequenced invasive<jats:italic>S. pyogenes</jats:italic>isolates that included the two intermediate lineages. The assay was then applied to DNA from all 305 invasive<jats:italic>emm</jats:italic>1 isolates that had been submitted to the reference laboratory in the one pear period Jan 1-Dec 31 2020, in order to assign lineage.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The allele sp
Price V, Ngwira LG, Lewis JM, et al., 2022, A systematic review of economic evaluations of whole genome sequencing for the surveillance of bacterial pathogens, Microbial Genomics, ISSN: 2057-5858
Rodgus J, Prakapaite R, Mitsidis P, et al., 2022, Molecular epidemiology of Group B streptococci in Lithuania identifies multi-drug resistant clones and sporadic ST1 serotypes Ia and Ib, Pathogens, Vol: 11, Pages: 1-11, ISSN: 2076-0817
Streptococcus agalactiae (Group B Streptococcus, GBS) is a leading cause of neonatal infections. Yet, detailed assessment of the genotypic and phenotypic factors associated with GBS carriage, mother-to-baby transmission, and GBS infection in neonates and adults is lacking. Understanding the distribution of GBS genotypes, including the predominance of different serotypes, antimicrobial resistance (AMR) genes, and virulence factors, is likely to help to prevent GBS diseases, as well as inform estimates of the efficacy of future GBS vaccines. To this end, we set out to characterise GBS isolates collected from pregnant and non-pregnant women in Kaunas region in Lithuania. Whole genome sequences of 42 GBS isolates were analysed to determine multi-locus sequence typing (MLST), the presence of acquired AMR and surface protein genes, and the phylogenetic relatedness of isolates. We identified serotypes Ia (42.9%, 18/42), III (33.3%, 14/42), V (21.4%, 9/42), and a single isolate of serotype Ib. Genomic analyses revealed high diversity among isolates, with 18 sequence types (STs) identified, including three novel STs. 85.7% (36/42) of isolates carried at least one AMR gene: tetM or tetO (35/42), ermB or lsaC (8/42) and ant6-Ia and aph3-III (2/42). This study represents the first genomic analysis of GBS isolated from women in Lithuania and contributes to an improved understanding of the global spread of GBS genotypes and phenotypes, laying the foundations for future GBS surveillance in Lithuania.
Jauneikaite E, Honeyford K, Blandy O, et al., 2022, Bacterial genotypic and patient risk factors for adverse outcomes in Escherichia coli bloodstream infections: a prospective molecular-epidemiological study, Journal of Antimicrobial Chemotherapy, Vol: 77, Pages: 1753-1761, ISSN: 0305-7453
Objectives:Escherichia coli bloodstream infections have shown a sustained increase in England, for reasons that are unknown. Furthermore, the contribution of multi-drug resistant lineages such as ST131 to overall E. coli disease burden and outcome is undetermined. Methods:We genome sequenced E. coli blood isolates from all patients with E. coli bacteraemia in north-west London from July 2015 to August 2016 and assigned multi-locus sequence types, virulence factors, and AMR genes to all isolates. Isolate sequence types were then linked to phenotypic antimicrobial susceptibility, patient demographic, and clinical outcome data to explore relationships between the E. coli sequence types, patient factors, and outcomes. Results:A total of 551 E. coli genomes were analysed. Four sequence types (ST131, 21.2%; ST73, 14.5%; ST69, 9.3%; and ST95, 8.2%) accounted for over half of cases. E. coli genotype ST131-C2 was associated with phenotypic non-susceptibility to quinolones, third-generation cephalosporins, amoxicillin, amoxicillin-clavulanic acid, gentamicin, and trimethoprim. Among 300 patients from whom outcome was known, an association between the ST131-C2 lineage and longer length-of-stay was detected, although multivariable regression modelling did not demonstrate an association between E. coli sequence type and mortality. Several unexpected associations were identified between gentamicin non-susceptibility; ethnicity; sex and adverse outcomes, requiring further research.Conclusions:Although E. coli sequence type was associated with defined antimicrobial non-susceptibility patterns and prolonged length-of-stay, E. coli sequence type was not associated with increased mortality. ST131 has outcompeted other lineages in north-west London. Where ST131 is prevalent, caution is required when devising empiric regimens for suspected Gram-negative sepsis, in particular the pairing of beta-lactam agents with gentamicin.
Imai N, Gaythorpe K, Bhatia S, et al., 2022, COVID-19 in Japan, January – March 2020: insights from the first three months of the epidemic, BMC Infectious Diseases, Vol: 22, ISSN: 1471-2334
Background:Understanding the characteristics and natural history of novel pathogens is crucial to inform successful control measures. Japan was one of the first affected countries in the COVID-19 pandemic reporting their first case on 14 January 2020. Interventions including airport screening, contact tracing, and cluster investigations were quickly implemented. Here we present insights from the first 3 months of the epidemic in Japan based on detailed case data. Methods:We conducted descriptive analyses based on information systematically extracted from individual case reports from 13 January to 31 March 2020 including patient demographics, date of report and symptom onset, symptom progression, travel history, and contact type. We analysed symptom progression and estimated the time-varying reproduction number, Rt, correcting for epidemic growth using an established Bayesian framework. Key delays and the age-specific probability of transmission were estimated using data on exposures and transmission pairs. Results:The corrected fitted mean onset-to-reporting delay after the peak was 4 days (standard deviation: ±2 days). Early transmission was driven primarily by returning travellers with Rt peaking at 2.4 (95%CrI:1.6, 3.3) nationally. In the final week of the trusted period (16 – 23 March 2020), Rt accounting for importations diverged from overall Rt at 1.1 (95% CrI: 1.0, 1.2) compared to 1.5 (95% CrI: 1.3, 1.6) respectively. Household (39.0%) and workplace (11.6%) exposures were the most frequently reported potential source of infection. The estimated probability of transmission was assortative by age with individuals more likely to infect, and be infected by, contacts in a similar age group to them. Across all age groups, cases most frequently onset with cough, fever, and fatigue. There were no reported cases of patients <20 years old developing pneumonia or severe respiratory symptoms.Conclusions:Information collected in the early phases of an out
Taylor E, Jauneikaite E, Sriskandan S, et al., 2022, Novel 16S rRNA methyltransferase RmtE3 in acinetobacter baumannii ST79., Journal of Medical Microbiology, Vol: 71, ISSN: 0022-2615
Introduction. The 16S rRNA methyltransferase (16S RMTase) gene armA is the most common mechanism conferring high-level aminoglycoside resistance in Acinetobacter baumannii, although rmtA, rmtB, rmtC, rmtD and rmtE have also been reported.Hypothesis/Gap statement. The occurrence of 16S RMTase genes in A. baumannii in the UK and Republic of Ireland is currently unknown.Aim. To identify the occurrence of 16S RMTase genes in A. baumannii isolates from the UK and the Republic of Ireland between 2004 and 2015.Methodology. Five hundred and fifty pan-aminoglycoside-resistant A. baumannii isolates isolated from the UK and the Republic of Ireland between 2004 and 2015 were screened by PCR to detect known 16S RMTase genes, and then whole-genome sequencing was conducted to screen for novel 16S RMTase genes.Results. A total of 96.5 % (531/550) of isolates were positive for 16S RMTase genes, with all but 1 harbouring armA (99.8 %, 530/531). The remaining isolates harboured rmtE3, a new rmtE variant. Most (89.2 %, 473/530) armA-positive isolates belonged to international clone II (ST2), and the rmtE3-positive isolate belonged to ST79. rmtE3 shared a similar genetic environment to rmtE2 but lacked an ISCR20 element found upstream of rmtE2.Conclusion. This is the first report of rmtE in A. baumannii in Europe; the potential for transmission of rmtE3 to other bacterial species requires further research.
Cordery R, Purba A, Begum L, et al., 2022, Frequency of transmission, asymptomatic shedding, and airborne spread of Streptococcus pyogenes in schoolchildren exposed to scarlet fever: a prospective, longitudinal, multicohort, molecular epidemiological, contact-tracing study in England, UK, The Lancet Microbe, Vol: 3, Pages: e366-e375, ISSN: 2666-5247
BackgroundDespite recommendations regarding prompt treatment of cases and enhanced hygiene measures, scarlet fever outbreaks increased in England between 2014 and 2018. We aimed to assess the effects of standard interventions on transmission of Streptococcus pyogenes to classroom contacts, households, and classroom environments to inform future guidance.MethodsWe did a prospective, longitudinal, multicohort, molecular epidemiological, contact-tracing study in six settings across five schools in Greater London, UK. Schools and nurseries were eligible to participate if they had reported two cases of scarlet fever within 10 days of each other among children aged 2–8 years from the same class, with the most recent case arising in the preceding 48 h. We cultured throat swabs from children with scarlet fever, classroom contacts, and household contacts at four timepoints. We also cultured hand swabs and cough plates from all cases in years 1 and 2 of the study, and from classroom contacts in year 2. Surface swabs from toys and other fomites in classrooms were cultured in year 1, and settle plates from classrooms were collected in year 2. Any sample with S pyogenes detected was recorded as positive and underwent emm genotyping and genome sequencing to compare with the outbreak strain.FindingsSix classes, comprising 12 cases of scarlet fever, 17 household contacts, and 278 classroom contacts were recruited between March 1 and May 31, 2018 (year 1), and between March 1 and May 31, 2019 (year 2). Asymptomatic throat carriage of the outbreak strains increased from 11 (10%) of 115 swabbed children in week 1, to 34 (27%) of 126 in week 2, to 26 (24%) of 108 in week 3, and then five (14%) of 35 in week 4. Compared with carriage of outbreak S pyogenes strains, colonisation with non-outbreak and non-genotyped S pyogenes strains occurred in two (2%) of 115 swabbed children in week 1, five (4%) of 126 in week 2, six (6%) of 108 in week 3, and in none of the 35 children in week 4
Ledda A, Cummins M, Shaw LP, et al., 2022, Hospital outbreak of carbapenem-resistant Enterobacterales associated with a bla OXA-48 plasmid carried mostly by Escherichia coli ST399, Microbial Genomics, Vol: 8, ISSN: 2057-5858
A hospital outbreak of carbapenem-resistant Enterobacterales was detected by routine surveillance. Whole genome sequencing and subsequent analysis revealed a conserved promiscuous blaOXA-48 carrying plasmid as the defining factor within this outbreak. Four different species of Enterobacterales were involved in the outbreak. Escherichia coli ST399 accounted for 35 of all the 55 isolates. Comparative genomics analysis using publicly available E. coli ST399 genomes showed that the outbreak E. coli ST399 isolates formed a unique clade. We developed a mathematical model of pOXA-48-like plasmid transmission between host lineages and used it to estimate its conjugation rate, giving a lower bound of 0.23 conjugation events per lineage per year. Our analysis suggests that co-evolution between the pOXA-48-like plasmid and E. coli ST399 could have played a role in the outbreak. This is the first study to report carbapenem-resistant E. coli ST399 carrying blaOXA-48 as the main cause of a plasmid-borne outbreak within a hospital setting. Our findings suggest complementary roles for both plasmid conjugation and clonal expansion in the emergence of this outbreak.
Khan U, Jauneikaite E, Andrews R, et al., 2022, Identifying large-scale recombination and capsular switching events in Streptococcus agalactiae strains causing disease in adults in the United Kingdom between 2014 and 2015, Microbial Genomics, Vol: 8, ISSN: 2057-5858
Cases of invasive Group B Streptococcal infections in the adult UK population have steadily increased over recent years, with most common serotypes being V, III and Ia, but less is known of the genetic background of these strains. We have carried out in-depth analysis of whole genome sequences of 193 clinically important GBS isolates (186 were from invasive and 7 were from non-invasive infection) isolated from adults and submitted to the National Reference Laboratory at UK Health Security Agency between January 2014 and December 2015. We have determined that capsular serotypes III (26.8%), Ia (26.2%) and V (14.9%) were most commonly identified, with slight differences in gender and age distribution. Most isolates (n=185) grouped to 5 clonal complexes: CC1, CC8, CC17, CC19 and CC23 with common associations between specific serotypes and virulence genes. Additionally, we have identified large recombination events mediating potential capsular switching events between ST1 serotype V and serotypes Ib (n=2 isolates), II (n=2 isolates) and VI (n=2 isolates); ST19 serotype III and serotype V (n=5 isolates); CC17 serotype III and serotype IV (n=1 isolate).The high genetic diversity of disease-causing isolates and multiple recombination events reported in this study, highlight the need for routine surveillance of the circulating disease-causing GBS strains. This information is crucial to better understand global spread of GBS serotypes and genotypes and will form the baseline information for any future GBS vaccine research in the UK and worldwide. Impact statementThis study is the first study to report on in-depth genomic analysis of the disease-causing GBS in adult population in the UK. We describe the most common serotype-genotype combinations, including multi-locus sequence types (MLST) and major virulence gene combinations for the specific serotypes, found in our dataset. Importantly, we report on various potential capsular type switching caused by recombination events fo
Taylor E, Jauneikaite E, Sriskandan S, et al., 2022, Detection and characterisation of 16S rRNA methyltransferase-producing Pseudomonas aeruginosa from the UK and Republic of Ireland from 2003-2015, International Journal of Antimicrobial Agents, Vol: 59, ISSN: 0924-8579
16S rRNA methyltransferase (16S RMTase) genes confer high-level aminoglycoside resistance, reducing treatment options for multidrug-resistant Gram-negative bacteria. Pseudomonas aeruginosa isolates (n = 221) exhibiting high-level pan-aminoglycoside resistance (amikacin, gentamicin and tobramycin MICs ≥64, ≥32 and ≥32 mg/L, respectively) were screened for 16S RMTase genes to determine their occurrence among isolates submitted to a national reference laboratory from December 2003 to December 2015. 16S RMTase genes were identified using two multiplex PCRs, and whole-genome sequencing (WGS) was used to identify other antibiotic resistance genes, sequence types (STs) and the genetic environment of 16S RMTase genes. 16S RMTase genes were found in 8.6% (19/221) of isolates, with rmtB4 (47.4%; 9/19) being most common, followed by rmtD3 (21.1%; 4/19), rmtF2 (15.8%; 3/19) and single isolates harbouring rmtB1, rmtC and rmtD1. Carbapenemase genes were found in 89.5% (17/19) of 16S RMTase-positive isolates, with blaVIM (52.9%; 9/17) being most common. 16S RMTase genes were found in ‘high-risk’ clones known to harbour carbapenemase genes (ST233, ST277, ST357, ST654 and ST773). Analysis of the genetic environment of 16S RMTase genes identified that IS6100 was genetically linked to rmtB1; IS91 to rmtB4, rmtC or rmtD3; ISCR14 to rmtD1; and rmtF2 was linked to Tn3, IS91 or Tn1721. Although 16S RMTase genes explained only 8.6% of pan-aminoglycoside resistance in the P. aeruginosa isolates studied, the association of 16S RMTase genes with carbapenemase-producers and ‘high-risk’ clones highlights that continued surveillance is required to monitor spread as well as the importance of suppressing the emergence of dually-resistant clones in hospital settings.
Myall A, Peach R, Wan Y, et al., 2022, Improved contact tracing using network analysis and spatial-temporal proximity, iMED conference, Publisher: Elsevier, Pages: S20-S20, ISSN: 1201-9712
Imai N, Gaythorpe KAM, Bhatia S, et al., 2022, COVID-19 in Japan: insights from the first three months of the epidemic, Publisher: Cold Spring Harbor Laboratory
BackgroundUnderstanding the characteristics and natural history of novel pathogens is crucial to inform successful control measures. Japan was one of the first affected countries in the COVID-19 pandemic reporting their first case on 14 January 2020. Interventions including airport screening, contact tracing, and cluster investigations were quickly implemented. Here we present insights from the first 3 months of the epidemic in Japan based on detailed case data. MethodsWe conducted descriptive analyses based on information systematically extracted from individual case reports from 13 January to 31 March 2020 including patient demographics, date of report and symptom onset, symptom progression, travel history, and contact type. We analysed symptom progression and estimated the time-varying reproduction number, Rt, correcting for epidemic growth using an established Bayesian framework. Key delays and the age-specific probability of transmission were estimated using data on exposures and transmission pairs. ResultsThe corrected fitted mean onset-to-reporting delay after the peak was 4 days (standard deviation: ±2 days). Early transmission was driven primarily by returning travellers with Rt peaking at 2.4 (95%CrI:1.6, 3.3) nationally. In the final week of the trusted period, Rt accounting for importations diverged from overall Rt at 1.1 (95% CrI: 1.0, 1.2) compared to 1.5 (95% CrI: 1.3, 1.6) respectively. Household (39.0%) and workplace (11.6%) exposures were the most frequently reported potential source of infection. The estimated probability of transmission was assortative by age. Across all age groups, cases most frequently onset with cough, fever, and fatigue. There were no reported cases of patients <20 years old developing pneumonia or severe respiratory symptoms.ConclusionsInformation collected in the early phases of an outbreak are important in characterising any novel pathogen. Timely recognition of key symptoms and high-risk settings for transmi
Aliabadi S, Jauneikaite E, Muller-Pebody B, et al., 2021, Exploring temporal trends and risk factors for resistance in Escherichia coli-causing bacteraemia in England between 2013 and 2018: an ecological study, JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, Vol: 77, Pages: 782-792, ISSN: 0305-7453
Wan Y, Mills E, Leung RCY, et al., 2021, Alterations in chromosomal genes nfsA, nfsB, and ribE are associated with nitrofurantoin resistance in escherichia coli from the UK, Microbial Genomics, Vol: 7, Pages: 1-19, ISSN: 2057-5858
Antimicrobial resistance in enteric or urinary Escherichia coli is a risk factor for invasive E. coli infections. Due to widespread trimethoprim resistance amongst urinary E. coli and increased bacteraemia incidence, a national recommendation to prescribe nitrofurantoin for uncomplicated urinary tract infection was made in 2014. Nitrofurantoin resistance is reported in <6% urinary E. coli isolates in the UK, however, mechanisms underpinning nitrofurantoin resistance in these isolates remain unknown. This study aimed to identify the genetic basis of nitrofurantoin resistance in urinary E. coli isolates collected from north west London and then elucidate resistance-associated genetic alterations in available UK E. coli genomes. As a result, an algorithm was developed to predict nitrofurantoin susceptibility.Deleterious mutations and gene-inactivating insertion sequences in chromosomal nitroreductase genes nfsA and/or nfsB were identified in genomes of nine nitrofurantoin-resistant urinary E. coli isolates, as well as all further 11 E. coli isolates that were experimentally validated to be nitrofurantoin resistant. Eight categories of allelic changes in nfsA, nfsB, and the associated gene ribE were detected in 12,412 E. coli genomes from the UK. Evolutionary analysis of these three genes revealed homoplasic mutations and explained the previously reported order of stepwise mutations. The mobile gene complex oqxAB, which is associated with reduced nitrofurantoin susceptibility, was identified in only one of the 12,412 genomes.In conclusion, mutations and insertion sequences in nfsA and nfsB were leading causes of nitrofurantoin resistance in UK E. coli. As nitrofurantoin exposure increases in human populations, the prevalence of nitrofurantoin resistance in carriage E. coli isolates and those from urinary and bloodstream infections should be monitored.
Aliabadi S, Anyanwu P, Beech E, et al., 2021, Do antibiotic stewardship interventions in primary care have an effect on antimicrobial resistance of Escherichia coli bacteraemia in England? An ecological analysis of national data between 2013-2018, The Lancet Infectious Diseases, Vol: 21, ISSN: 1473-3099
Background: We sought to evaluate the effectiveness of a national antimicrobial stewardship intervention, the Quality Premium (QP), on broad-spectrum antibiotic prescribing and Escherichia coli bacteraemia resistance to broad-spectrum antibiotics in England. Methods: We used longitudinal data on patients registered with a general practitioner in the English National Health Service and patients with E. coli bacteraemia notified to the national mandatory surveillance programme between January 2013-December 2018.We conducted an ecological analysis using interrupted time series (ITS) analyses and generalised estimating equations (GEE) to estimate the change in broad-spectrum antibiotics prescribing over time and change in the proportion of E. coli bacteraemia cases where the causative bacteria were resistant to each antibiotic individually or to at least one of the five antibiotics, after implementation of the QP. Findings: Following the implementation of the QP in April 2015, we observed an immediate downward step-change in broad-spectrum antibiotic prescribing incidence rate of 0.867per 1000 patients (95% CI: 0.837 to 0.898, p<0·001). We found that the pre-intervention slope for total antibiotic usage was an IRR of 1.002(CI: 1.000to 1.004, p-value=0.046). The change in slope for total antibiotic usage was an IRR of 0.993(CI: 0.991to 0.995, p<0·001). We also observed a downward step-change in resistance rate of 0.947 per 1000 E. coli isolates tested (95% CI: 0.918 to 0.977, p<0·001).We found that the pre-intervention slope for total antibiotic resistance was an IRR of 1.001 (CI: 0.999 to 1.003, p-value=0.346). The change in slope level for total antibiotic usage was an IRR of 0.999 (CI: 0.997 to 1.000, p=0.112). On examination of the long-term effect following implementation of the QP, there was an increase in the number of isolates resistant to at least one of the five broad-spectrum antibiotics tested.134Interpretati
To K-N, Powell O, Jamrozy D, et al., 2021, RAPD PCR detects co-colonisation of multiple Group B Streptococcus genotypes: a practical molecular technique for screening multiple colonies, Journal of Microbiological Methods, Vol: 190, ISSN: 0167-7012
Group B Streptococcus (GBS) is a leading cause of neonatal meningitis, pneumonia, and sepsis. The biggest contributing factor of neonatal infections is due to vertical transmission from maternal colonisation of GBS in the genitourinary tract. Multiple serotype colonisation is often not investigated in epidemiological studies, but it is an important consideration for serotype-based vaccine development and implementation to ensure less abundant serotypes are not under-represented. In this study, we show that RAPD PCR is a quick tool useful in screening the presence of genetically different strains using multiple colony picks from a single patient swab. We observed a maximum of five different GBS strains colonising a single patient at a specific time.
Miglietta L, Moniri A, Pennisi I, et al., 2021, Coupling machine learning and high throughput multiplex digital PCR enables accurate detection of carbapenem-resistant genes in clinical isolates, Frontiers in Molecular Biosciences, Vol: 8, Pages: 1-11, ISSN: 2296-889X
Rapid and accurate identification of patients colonised with carbapenemase-producing organisms (CPOs) is essential to adopt prompt prevention measures to reduce the risk of transmission. Recent studies have demonstrated the ability to combine machine learning (ML) algorithms with real-time digital PCR (dPCR) instruments to increase classification accuracy of multiplex PCR assays when using synthetic DNA templates. We sought to determine if this novel methodology could be applied to improve identification of the five major carbapenem-resistant genes in clinical CPO-isolates, which would represent a leap forward in the use of PCR-based data-driven diagnostics for clinical applications. We collected 3 clinical isolates (including 221 CPO-positive samples) and developed a novel 5-plex PCR assay for detection of blaIMP, blaKPC, blaNDM, blaOXA-48 and blaVIM. Combining the recently reported ML method ‘Amplification and Melting Curve Analysis’ (AMCA) with the abovementioned multiplex assay, we assessed the performance of the AMCA methodology in detecting these genes. The improved classification accuracy of AMCA relies on the usage of real-time data from a single fluorescent channel and benefits from the kinetic/thermodynamic information encoded in the thousands of amplification events produced by high throughput real-time dPCR. The 5-plex showed a lower limit of detection of 10 DNA copies per reaction for each primer set and no cross-reactivity with other carbapenemase genes. The AMCA classifier demonstrated excellentpredictive performance with 99.6% (CI 97.8-99.9%) accuracy (only one misclassified sample out of the 253, with a total of 160,041 positive amplification events), which represents a 7.9% increase (p value < 0.05) compared to conventional melting curve analysis. This work demonstrates the use of the AMCA method to increase the throughput and performance of state-of-the-art molecular diagnostic platforms, without hardware modifications and additiona
Wan Y, Myall AC, Boonyasiri A, et al., 2021, Integrated analysis of patient networks and plasmid genomes reveals a regional, multi-species outbreak of carbapenemase-producing Enterobacterales carrying both<i>bla</i><sub>IMP</sub>and<i>mcr-9</i>genes
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Carbapenemase-producing Enterobacterales (CPE) are challenging in the healthcare setting, with resistance to multiple classes of antibiotics and a high associated mortality. The incidence of CPE is rising globally, despite enhanced awareness and control efforts. This study describes an investigation of the emergence of IMP-encoding CPE amongst diverse Enterobacterales species between 2016 and 2019 in patients across a London regional hospital network.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We carried out a network analysis of patient pathways, using electronic health records, to identify contacts between IMP-encoding CPE positive patients. Genomes of IMP-encoding CPE isolates were analysed and overlayed with patient contacts to imply potential transmission events.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Genomic analysis of 84 Enterobacterales isolates revealed diverse species (predominantly<jats:italic>Klebsiella</jats:italic>spp,<jats:italic>Enterobacter</jats:italic>spp,<jats:italic>E. coli</jats:italic>), of which 86% (72/84) harboured an IncHI2 plasmid, which carried both<jats:italic>bla</jats:italic><jats:sub>IMP</jats:sub>and the mobile colistin resistance gene<jats:italic>mcr-9</jats:italic>(68/72). Phylogenetic analysis of IncHI2 plasmids identified three lineages which showed significant association with patient contact and movements between four hospital sites and across medical specialities, which had been missed on initial investigations.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Combined, our patient network and plasmid analyses demonstrate an interspecies, plasmid-med
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