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Transferable linezolid resistance due to optrA, poxtA, cfr and cfr-like genes is increasingly detected in enterococci associated with animals and humans globally. We aimed to characterize the genetic environment of optrA in linezolid-resistant Enterococcus faecalis isolates from Scotland. Six linezolid-resistant E. faecalis isolated from urogenital samples were confirmed to carry the optrA gene by PCR. Short read (Illumina) sequencing showed the isolates were genetically distinct (>13900 core SNPs) and belonged to different MLST sequence types. Plasmid contents were examined using hybrid assembly of short and long read (Oxford Nanopore MinION) sequencing technologies. The optrA gene was located on distinct plasmids in each isolate, suggesting that transfer of a single plasmid did not contribute to optrA dissemination in this collection. pTM6294-2, BX5936-1 and pWE0438-1 were similar to optrA-positive plasmids from China and Japan, while the remaining three plasmids had limited similarity to other published examples. We identified the novel Tn6993 transposon in pWE0254-1 carrying linezolid (optrA), macrolide (ermB) and spectinomycin [ANT(9)-Ia] resistance genes. OptrA amino acid sequences differed by 0-20 residues. We report multiple variants of optrA on distinct plasmids in diverse strains of E. faecalis. It is important to identify the selection pressures driving the emergence and maintenance of resistance against linezolid to retain the clinical utility of this antibiotic.
Assuntos
Enterococcus faecium , Infecções por Bactérias Gram-Positivas , Animais , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Enterococcus faecalis/genética , Enterococcus faecium/genética , Linezolida/farmacologia , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Plasmídeos/genéticaRESUMO
To maintain patient flow during the COVID-19 pandemic, rapid and accurate decisions for the safe triage of geriatrics patients was essential as turnaround times for laboratory testing was ineffective at supporting rapid clinical decision-making for transfer of care. Thus, to mitigate and inform these clinical decisions, a quality improvement collaborative project with the geriatrics and virology department was conducted at the Frailty Assessment Unit (FAU) at Aberdeen Royal Infirmary. The goal was to facilitate patient triage during transfer of care with the introduction of Point of Care testing (POCT). The interventions which resulted in significant improvements were based on the fishbone problem solving approach and the driver diagram with change ideas informing the five Plan, Do, Study and Act (PDSA) cycles. The QI intervention was crucial in supporting clinical staff decision making during transfers for 95% of patients who had been clinically judged as asymptomatic for COVID-19 infection. High staff engagement was observed with 83% of staff suggesting the process map was easy to follow and 92% of clinical staff agreed it contained sufficient information to support the testing process. With POCT introduction, the proportion of patients who were transferred with an early POCT result increased by 20% in the Rosewell House group and by 65% in the community Hospitals group, once governance arrangements were in place. Finally, the considerable uptake of POCT by the ward consequently led to a decrease of up to 86% in the number of samples sent to the laboratory for rapid SARS-CoV-2 testing. The quality improvement project provided a rapid and reliable SARS-CoV-2 triage tool and was effectively integrated into the geriatrics triage algorithm to facilitate patient placement and flow.
Assuntos
COVID-19 , Fragilidade , Humanos , SARS-CoV-2 , COVID-19/diagnóstico , Melhoria de Qualidade , Teste para COVID-19 , Pandemias , Testes ImediatosRESUMO
OBJECTIVES: To determine how the intrinsic severity of successively dominant SARS-CoV-2 variants changed over the course of the pandemic. METHODS: A retrospective cohort analysis in the NHS Greater Glasgow and Clyde (NHS GGC) Health Board. All sequenced non-nosocomial adult COVID-19 cases in NHS GGC with relevant SARS-CoV-2 lineages (B.1.177/Alpha, Alpha/Delta, AY.4.2 Delta/non-AY.4.2 Delta, non-AY.4.2 Delta/Omicron, and BA.1 Omicron/BA.2 Omicron) during analysis periods were included. Outcome measures were hospital admission, ICU admission, or death within 28 days of positive COVID-19 test. We report the cumulative odds ratio; the ratio of the odds that an individual experiences a severity event of a given level vs all lower severity levels for the resident and the replacement variant after adjustment. RESULTS: After adjustment for covariates, the cumulative odds ratio was 1.51 (95% CI: 1.08-2.11) for Alpha versus B.1.177, 2.09 (95% CI: 1.42-3.08) for Delta versus Alpha, 0.99 (95% CI: 0.76-1.27) for AY.4.2 Delta versus non-AY.4.2 Delta, 0.49 (95% CI: 0.22-1.06) for Omicron versus non-AY.4.2 Delta, and 0.86 (95% CI: 0.68-1.09) for BA.2 Omicron versus BA.1 Omicron. CONCLUSIONS: The direction of change in intrinsic severity between successively emerging SARS-CoV-2 variants was inconsistent, reminding us that the intrinsic severity of future SARS-CoV-2 variants remains uncertain.
Assuntos
COVID-19 , SARS-CoV-2 , Adulto , Humanos , SARS-CoV-2/genética , Estudos Retrospectivos , HospitalizaçãoRESUMO
OBJECTIVES: The SARS-CoV-2 Alpha variant was associated with increased transmission relative to other variants present at the time of its emergence and several studies have shown an association between Alpha variant infection and increased hospitalisation and 28-day mortality. However, none have addressed the impact on maximum severity of illness in the general population classified by the level of respiratory support required, or death. We aimed to do this. METHODS: In this retrospective multi-centre clinical cohort sub-study of the COG-UK consortium, 1475 samples from Scottish hospitalised and community cases collected between 1st November 2020 and 30th January 2021 were sequenced. We matched sequence data to clinical outcomes as the Alpha variant became dominant in Scotland and modelled the association between Alpha variant infection and severe disease using a 4-point scale of maximum severity by 28 days: 1. no respiratory support, 2. supplemental oxygen, 3. ventilation and 4. death. RESULTS: Our cumulative generalised linear mixed model analyses found evidence (cumulative odds ratio: 1.40, 95% CI: 1.02, 1.93) of a positive association between increased clinical severity and lineage (Alpha variant versus pre-Alpha variants). CONCLUSIONS: The Alpha variant was associated with more severe clinical disease in the Scottish population than co-circulating lineages.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Estudos Retrospectivos , Escócia/epidemiologia , GenômicaRESUMO
Giardia duodenalis is a protozoan parasite known for its ability to cause gastrointestinal disease in human and non-human mammals. In the UK, the full impact of this parasite has yet to be fully explored, due to the limited testing which has been undertaken in humans and the low-resolution assemblage-typing methods currently available. Rather than being primarily a travel-associated condition, a recent study has highlighted that an endemic Giardia cycle is present in the UK, although the source of human disease is unclear in the majority of cases. This study focussed on the improvement of one of the commonly used assemblage-typing assays, a nested topoisomerase phosphate (tpi) PCR, to increase the amplification success rate across both human and companion animal samples. After comparing published primers to full Giardia reference genomes, this marker protocol was optimised and then deployed to test a substantial number of human (n â= â79) and companion animal (n â= â174) samples to gain an insight into the molecular epidemiology of Giardia in the UK. One assemblage A1 and eleven assemblage A2 genotypes were detected in humans, along with and 25 assemblage B genotypes. Assemblage A1 genotypes, known to be human-infective, were found in three feline and one canine sample, while one feline sample contained assemblage A2. Additionally, four feline samples contained assemblage B, which is recognised as potentially human-infective. This study demonstrates the presence of potentially human-infective Giardia genotypes circulating in the companion animal population, notably with 17.4% (8/46) of feline-derived Giardia strains being potentially zoonotic. Using a modified tpi-based genotyping assay, this work highlights the potential for domestic pets to be involved in the endemic transmission of giardiasis in the UK and underlines the need for appropriate hygiene measures to be observed when interacting with both symptomatic and asymptomatic animals. It also serves to underline the requirement for further studies to assess the zoonotic risk of Giardia associated with companion animals in high-income countries.
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INTRODUCTION: Urinary tract infection (UTI) is a common infection worldwide. The increase in multidrug resistance together with the paucity of new antibiotics highlights the need for alternative antimicrobials for management of UTI. Among which are older antimicrobials that had been used in the past and now were stopped. AREAS COVERED: In this article, we examine the evidence in literature for the value of use of various antimicrobial agents in UTI. We conducted systematic Pubmed search and journal literature review including early research work on older agents addressed in relation to recent clinical data. Antimicrobials reviewed include temocillin, fosfomycin, mecillinam, methenamine and cycloserine. We review mechanisms of action, spectrum of activity, effect on multidrug resistance, cure rates and patient tolerance. Expert commentary: Rational use of current agents and rehabilitation of older drugs will both be needed, combined with antibiotic stewardship, in order to contain the march of antibiotic resistance.