RESUMO
Since November 2023, the absolute number of attendances at emergency departments for pneumonia among children aged 5-14 years in England have been above expected levels for the time of year. This increased signal peaked during March 2024 but then persisted into early summer 2024 despite decreases in prevalence of seasonal respiratory pathogens. Record linkage between emergency department and laboratory databases points to this unusual activity being driven largely by Mycoplasma pneumoniae.
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Serviço Hospitalar de Emergência , Mycoplasma pneumoniae , Pneumonia , Humanos , Criança , Inglaterra/epidemiologia , Pré-Escolar , Adolescente , Incidência , Pneumonia/epidemiologia , Masculino , Feminino , Mycoplasma pneumoniae/isolamento & purificação , Serviço Hospitalar de Emergência/estatística & dados numéricos , Prevalência , Pneumonia por Mycoplasma/epidemiologia , Pneumonia por Mycoplasma/diagnóstico , Estações do Ano , Vigilância da PopulaçãoRESUMO
OBJECTIVES: Inappropriate prescribing of antibiotics is a key driver of antimicrobial resistance. This study aimed to describe urine sampling rates and antibiotic prescribing for patients with lower urinary tract infections (UTIs) in English general practice. DESIGN: A retrospective population-based study using administrative data. SETTING: IQVIA Medical Research Database (IMRD) data from general practices in England, 2015-2022. PARTICIPANTS: Patients who have consulted with an uncomplicated UTI in England general practices captured in the IMRD. OUTCOME MEASURES: Trends in UTI episodes (episodes were defined as UTI diagnosis codes occurring within 14 days of each other), testing and antibiotic prescribing on the same day as initial UTI consultation were assessed from January 2015 to December 2022. Associations, using univariate and multivariate logistic regressions, were examined between consultation and demographic factors on the odds of a urine test. RESULTS: There were 743 350 UTI episodes; 50.8% had a urine test. Testing rates fluctuated with an upward trend and large decline in 2020. Same-day UTI antibiotic prescribing occurred in 78.2% of episodes. In multivariate modelling, factors found to decrease odds of a urine test included age ≥85 years (0.83, 95% CI 0.82 to 0.84), consultation type (remote vs face to face, 0.45, 95% CI 0.45 to 0.46), episodes in London compared with the South (0.74, 95% CI 0.72 to 0.75) and increasing practice size (0.77, 95% CI 0.76 to 0.78). Odds of urine tests increased in males (OR 1.11, 95% CI 1.10 to 1.13), for those episodes without a same-day UTI antibiotic (1.10, 95% CI 1.04 to 1.16) for episodes for those with higher deprivation status (Indices of Multiple Deprivation 8 vs 1, 1.51, 95% CI 1.48 to 1.54). Compared with 2015, 2016-2019 saw increased odds of testing while 2020 and 2021 saw decreases, with 2022 showing increased odds. CONCLUSION: Urine testing for UTI in general practice in England showed an upward trend, with same-day antibiotic prescribing remaining consistent, suggesting greater alignment to national guidelines. The COVID-19 pandemic impacted testing rates, though as of 2022, they began to recover.
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Antibacterianos , Medicina Geral , Padrões de Prática Médica , Urinálise , Infecções Urinárias , Humanos , Inglaterra/epidemiologia , Infecções Urinárias/diagnóstico , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/urina , Infecções Urinárias/epidemiologia , Masculino , Feminino , Estudos Retrospectivos , Medicina Geral/tendências , Antibacterianos/uso terapêutico , Pessoa de Meia-Idade , Idoso , Urinálise/métodos , Padrões de Prática Médica/tendências , Padrões de Prática Médica/estatística & dados numéricos , Idoso de 80 Anos ou mais , Adulto , Prescrição Inadequada/estatística & dados numéricos , Adolescente , Adulto Jovem , Modelos LogísticosRESUMO
We describe an outbreak of Ralstonia pickettii in the United Kingdom, with isolates genetically indistinguishable from a 2023 Australian outbreak linked to internationally distributed saline solutions. Confirmed cases (n = 3) had bacteraemia, clinically relevant infection, indwelling venous lines and frequent healthcare contact. Multi-stakeholder intervention was required including product recall and risk communications. We recommend a low threshold for investigating clusters of Ralstonia species and similar opportunistic pathogens, considering contaminated product sources. Effective mitigation requires multi-agency partnership and international collaboration.
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Surtos de Doenças , Infecções por Bactérias Gram-Negativas , Ralstonia pickettii , Humanos , Reino Unido/epidemiologia , Ralstonia pickettii/isolamento & purificação , Ralstonia pickettii/genética , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Solução Salina , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Austrália/epidemiologia , Contaminação de Medicamentos , MasculinoRESUMO
The emergent fungal pathogen Candida auris is increasingly recognised as an important cause of healthcare-associated infections globally. It is highly transmissible, adaptable, and persistent, resulting in an organism with significant outbreak potential that risks devastating consequences. Progress in the ability to identify C. auris in clinical specimens is encouraging, but laboratory diagnostic capacity and surveillance systems are lacking in many countries. Intrinsic resistance to commonly used antifungals, combined with the ability to rapidly acquire resistance to therapy, substantially restricts treatment options and novel agents are desperately needed. Despite this, outbreaks can be interrupted, and mortality avoided or minimised, through the application of rigorous infection prevention and control measures with an increasing evidence base. This review provides an update on epidemiology, the impact of the COVID-19 pandemic, risk factors, identification and typing, resistance profiles, treatment, detection of colonisation, and infection prevention and control measures for C. auris. This review has informed a planned 2024 update to the United Kingdom Health Security Agency (UKHSA) guidance on the laboratory investigation, management, and infection prevention and control of Candida auris. A multidisciplinary response is needed to control C. auris transmission in a healthcare setting and should emphasise outbreak preparedness and response, rapid contact tracing and isolation or cohorting of patients and staff, strict hand hygiene and other infection prevention and control measures, dedicated or single-use equipment, appropriate disinfection, and effective communication concerning patient transfers and discharge.
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Antifúngicos , COVID-19 , Candida auris , Candidíase , Controle de Infecções , Humanos , Candidíase/prevenção & controle , Candidíase/epidemiologia , Candidíase/tratamento farmacológico , Candidíase/microbiologia , Controle de Infecções/métodos , Candida auris/efeitos dos fármacos , COVID-19/prevenção & controle , COVID-19/epidemiologia , Antifúngicos/uso terapêutico , Antifúngicos/farmacologia , Inglaterra/epidemiologia , Infecção Hospitalar/prevenção & controle , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , SARS-CoV-2 , Farmacorresistência Fúngica , Candida/efeitos dos fármacos , Candida/classificação , Candida/isolamento & purificação , Surtos de Doenças/prevenção & controleRESUMO
The UK observed a marked increase in scarlet fever and invasive group A streptococcal infection in 2022 with severe outcomes in children and similar trends worldwide. Here we report lineage M1UK to be the dominant source of invasive infections in this upsurge. Compared with ancestral M1global strains, invasive M1UK strains exhibit reduced genomic diversity and fewer mutations in two-component regulator genes covRS. The emergence of M1UK is dated to 2008. Following a bottleneck coinciding with the COVID-19 pandemic, three emergent M1UK clades underwent rapid nationwide expansion, despite lack of detection in previous years. All M1UK isolates thus-far sequenced globally have a phylogenetic origin in the UK, with dispersal of the new clades in Europe. While waning immunity may promote streptococcal epidemics, the genetic features of M1UK point to a fitness advantage in pathogenicity, and a striking ability to persist through population bottlenecks.
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COVID-19 , Filogenia , Infecções Estreptocócicas , Streptococcus pyogenes , Streptococcus pyogenes/genética , Streptococcus pyogenes/patogenicidade , Streptococcus pyogenes/isolamento & purificação , Reino Unido/epidemiologia , Humanos , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/microbiologia , COVID-19/epidemiologia , Pandemias , Escarlatina/epidemiologia , Escarlatina/microbiologia , Mutação , Proteínas Repressoras/genética , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Genoma Bacteriano , Europa (Continente)/epidemiologia , Proteínas de BactériasRESUMO
PURPOSE: Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection. The purpose of the study was to measure the associations of specific exposures (deprivation, ethnicity, and clinical characteristics) with incident sepsis and case fatality. METHODS: Two research databases in England were used including anonymized patient-level records from primary care linked to hospital admission, death certificate, and small-area deprivation. Sepsis cases aged 65-100 years were matched to up to six controls. Predictors for sepsis (including 60 clinical conditions) were evaluated using logistic and random forest models; case fatality rates were analyzed using logistic models. RESULTS: 108,317 community-acquired sepsis cases were analyzed. Severe frailty was strongly associated with the risk of developing sepsis (crude odds ratio [OR] 14.93; 95% confidence interval [CI] 14.37-15.52). The quintile with most deprived patients showed an increased sepsis risk (crude OR 1.48; 95% CI 1.45-1.51) compared to least deprived quintile. Strong predictors for sepsis included antibiotic exposure in prior 2 months, being house bound, having cancer, learning disability, and diabetes mellitus. Severely frail patients had a case fatality rate of 42.0% compared to 24.0% in non-frail patients (adjusted OR 1.53; 95% CI 1.41-1.65). Sepsis cases with recent prior antibiotic exposure died less frequently compared to non-users (adjusted OR 0.7; 95% CI 0.72-0.76). Case fatality strongly decreased over calendar time. CONCLUSION: Given the variety of predictors and their level of associations for developing sepsis, there is a need for prediction models for risk of developing sepsis that can help to target preventative antibiotic therapy.
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Atenção Primária à Saúde , Sepse , Humanos , Sepse/mortalidade , Sepse/epidemiologia , Idoso , Inglaterra/epidemiologia , Masculino , Feminino , Estudos de Casos e Controles , Idoso de 80 Anos ou mais , Atenção Primária à Saúde/estatística & dados numéricos , Fatores de Risco , Etnicidade/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Hospitais/estatística & dados numéricos , Infecções Comunitárias Adquiridas/mortalidade , Infecções Comunitárias Adquiridas/epidemiologiaAssuntos
Recidiva , Tonsilectomia , Tonsilite , Humanos , Tonsilite/cirurgia , Criança , Resultado do TratamentoRESUMO
BACKGROUND: People who inject drugs (PWID) are at increased risk of community-acquired Staphylococcus aureus bacteremia (CA-SAB), but little is known about clinical outcomes of CA-SAB in PWID compared with the wider population of patients with CA-SAB. METHODS: Three national datasets were linked to provide clinical and mortality data on patients hospitalized with CA-SAB in England between 1 January 2017 and 31 December 2020. PWID were identified using the International Classification of Diseases, Tenth Revision code for "mental health and behavioral disorder due to opioid use" (F11). Multivariable logistic regression was used to estimate adjusted odds ratios (aORs) for associations of PWID with 30-day all-cause mortality and 90-day hospital readmission. RESULTS: In 10 045 cases of CA-SAB, 1612 (16.0%) were PWID. Overall, 796 (7.9%) patients died within 30 days of CA-SAB admission and 1189 (11.8%) patients were readmitted to hospital within 90 days of CA-SAB. In those without infective endocarditis, there was strong evidence of lower odds of mortality among PWID compared with non-PWID (aOR, 0.47 [95% confidence interval {CI}: .33-.68]; P < .001), whereas there was no association in CA-SAB case fatality with endocarditis (aOR, 1.40 [95% CI: .87-2.25]; P = .163). PWID were less likely to be readmitted within 90 days of CA-SAB (aOR, 0.79 [95% CI: .65-.95]; P = .011). CONCLUSIONS: In this large cohort study of patients with CA-SAB in England, PWID had lower odds of death in the absence of endocarditis and lower odds of readmission within 90 days compared to non-PWID patients. This study highlights the overrepresentation of PWID among patients with CA-SAB nationally.
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Bacteriemia , Infecções Comunitárias Adquiridas , Infecções Estafilocócicas , Staphylococcus aureus , Abuso de Substâncias por Via Intravenosa , Humanos , Masculino , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/mortalidade , Feminino , Inglaterra/epidemiologia , Bacteriemia/epidemiologia , Bacteriemia/mortalidade , Adulto , Pessoa de Meia-Idade , Abuso de Substâncias por Via Intravenosa/complicações , Abuso de Substâncias por Via Intravenosa/epidemiologia , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Infecções Comunitárias Adquiridas/mortalidade , Estudos de Coortes , Readmissão do Paciente/estatística & dados numéricos , Idoso , Adulto Jovem , Fatores de RiscoRESUMO
BACKGROUND AND AIMS: Sepsis is a serious and life-threatening condition caused by a dysregulated immune response to an infection. Recent guidance issued in the UK gave recommendations around recognition and antibiotic treatment of sepsis, but did not consider factors relating to health inequalities. The aim of this study was to summarise the literature investigating associations between health inequalities and sepsis. METHODS: Searches were conducted in Embase for peer-reviewed articles published since 2010 that included sepsis in combination with one of the following five areas: socioeconomic status, race/ethnicity, community factors, medical needs and pregnancy/maternity. RESULTS: Five searches identified 1,402 studies, with 50 unique studies included in the review after screening (13 sociodemographic, 14 race/ethnicity, 3 community, 3 care/medical needs and 20 pregnancy/maternity; 3 papers examined multiple health inequalities). Most of the studies were conducted in the USA (31/50), with only four studies using UK data (all pregnancy related). Socioeconomic factors associated with increased sepsis incidence included lower socioeconomic status, unemployment and lower education level, although findings were not consistent across studies. For ethnicity, mixed results were reported. Living in a medically underserved area or being resident in a nursing home increased risk of sepsis. Mortality rates after sepsis were found to be higher in people living in rural areas or in those discharged to skilled nursing facilities while associations with ethnicity were mixed. Complications during delivery, caesarean-section delivery, increased deprivation and black and other ethnic minority race were associated with post-partum sepsis. CONCLUSION: There are clear correlations between sepsis morbidity and mortality and the presence of factors associated with health inequalities. To inform local guidance and drive public health measures, there is a need for studies conducted across more diverse setting and countries.
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Sepse , Humanos , Fatores de Risco , Feminino , Gravidez , Fatores Socioeconômicos , Etnicidade , Desigualdades de Saúde , Disparidades nos Níveis de SaúdeRESUMO
In 2022, there were global reports of increased numbers of acute hepatitis not explained by hepatitis A-E virus infection in children. This manuscript summarises histopathology results from 20 patients in the United Kingdom who underwent liver transplant or had a liver biopsy as part of aetiological investigations. All available histopathological samples were reviewed centrally as part of the outbreak investigation. A working group comprised of infection specialists, hepatologists and histopathologists met virtually to review the cases, presentation, investigations and histopathology. All 20 liver samples had evidence of inflammation without significant interface activity, and submassive confluent pan-lobular or multilobular hepatocellular necrosis. Overall, the predominant histopathological findings were of acute nonspecific hepatitis with submassive hepatic necrosis and central vein perivenulitis and endothelitis. Histopathological findings were a poor indicator of aetiology.
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Hepatite , Hepatopatias , Transplante de Fígado , Humanos , Criança , Fígado/patologia , Hepatite/patologia , Hepatopatias/patologia , BiópsiaRESUMO
OBJECTIVE: Staphylococcus capitis, a coagulase-negative staphylococci (CoNS) species, has been increasingly detected from UK sterile site samples and has caused neonatal unit outbreaks worldwide. We compared survival to discharge and 30-day mortality for the detection of S. capitis versus other CoNS species. METHODS: In this retrospective case-control study, we included hospitalised infants with any CoNS species detected from a normally sterile body site up to 90 days of age. We linked English laboratory reports from the Second Generation Surveillance System database, mortality data from the Personal Demographics Service, and neonatal unit admissions from the National Neonatal Research Database. In primary analysis, multivariable logistic regression was used, with two co-primary outcomes: survival to discharge and death within 30 days of positive specimen date. Sensitivity analyses using multiply imputed datasets followed. RESULTS: We identified 16 636 CoNS episodes relating to 13 745 infants. CoNS episodes were highest among infants born extremely preterm (22-27 weeks) and with extremely low birth weight (400-999 g). In primary analysis, there were no differences in survival to discharge (p=0.71) or 30-day mortality (p=0.77) between CoNS species. In sensitivity analyses, there were no differences in outcomes between infection with four of the most common CoNS species (Staphylococcus epidermidis, S. capitis, Staphylococcus haemolyticus and Staphylococcus warneri) but the remaining CoNS species were at higher risk of adverse outcomes when treated in aggregate. CONCLUSION: Infants with S. capitis detected from sterile site samples did not experience significant differences in either survival to discharge or 30-day mortality compared with infants with detection of other common CoNS species.
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Infecções Estafilocócicas , Staphylococcus capitis , Humanos , Recém-Nascido , Estudos de Casos e Controles , Inglaterra/epidemiologia , Estudos Retrospectivos , Infecções Estafilocócicas/epidemiologia , Lactente Extremamente Prematuro , Nascimento PrematuroRESUMO
Third doses of COVID-19 vaccines were widely deployed following the primary vaccine course waning and the emergence of the Omicron-variant. We investigated protection from third-dose vaccines and previous infection against SARS-CoV-2 infection during Delta-variant and Omicron-variant (BA.1 & BA.2) waves in our frequently PCR-tested cohort of healthcare-workers. Relative effectiveness of BNT162b2 third doses and infection-acquired immunity was assessed by comparing the time to PCR-confirmed infection in boosted participants with those with waned dose-2 protection (≥254 days after dose-2), by primary series vaccination type. Follow-up time was divided by dominant circulating variant: Delta 07 September 2021 to 30 November 2021, Omicron 13 December 2021t o 28 February 2022. We used a Cox regression model with adjustment/stratification for demographic characteristics and staff-type. We explored protection associated with vaccination, infection and both. We included 19,614 participants, 29% previously infected. There were 278 primary infections (4 per 10,000 person-days of follow-up) and 85 reinfections (0.8/10,000 person-days) during the Delta period and 2467 primary infections (43/10,000 person-days) and 881 reinfections (33/10,000) during the Omicron period. Relative Vaccine Effectiveness (VE) 0-2 months post-3rd dose (3rd dose) (3-doses BNT162b2) in the previously uninfected cohort against Delta infections was 63% (95% Confidence Interval (CI) 40%-77%) and was lower (35%) against Omicron infection (95% CI 21%-47%). The relative VE of 3rd dose (heterologous BNT162b2) was greater for primary course ChAdOX1 recipients, with VE 0-2 months post-3rd dose over ≥68% higher for both variants. Third-dose protection waned rapidly against Omicron, with no significant difference between two and three BNT162b2 doses observed after 4-months. Previous infection continued to provide additional protection against Omicron (67% (CI 56%-75%) 3-6 months post-infection), but this waned to about 25% after 9-months, approximately three times lower than against Delta. Infection rates surged with Omicron emergence. Third doses of BNT162b2 vaccine provided short-term protection, with rapid waning against Omicron infections. Protection associated with infections incurred before Omicron was markedly diminished against the Omicron wave. Our findings demonstrate the complexity of an evolving pandemic with the potential emergence of immune-escape variants and the importance of continued monitoring.
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Vacina BNT162 , COVID-19 , Humanos , Estudos de Coortes , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Vacinas de mRNA , Reinfecção , SARS-CoV-2 , Reino Unido/epidemiologiaRESUMO
Background: The protection of fourth dose mRNA vaccination against SARS-CoV-2 is relevant to current global policy decisions regarding ongoing booster roll-out. We aimed to estimate the effect of fourth dose vaccination, prior infection, and duration of PCR positivity in a highly-vaccinated and largely prior-COVID-19 infected cohort of UK healthcare workers. Methods: Participants underwent fortnightly PCR and regular antibody testing for SARS-CoV-2 and completed symptoms questionnaires. A multi-state model was used to estimate vaccine effectiveness (VE) against infection from a fourth dose compared to a waned third dose, with protection from prior infection and duration of PCR positivity jointly estimated. Findings: 1298 infections were detected among 9560 individuals under active follow-up between September 2022 and March 2023. Compared to a waned third dose, fourth dose VE was 13.1% (95% CI 0.9 to 23.8) overall; 24.0% (95% CI 8.5 to 36.8) in the first 2 months post-vaccination, reducing to 10.3% (95% CI -11.4 to 27.8) and 1.7% (95% CI -17.0 to 17.4) at 2-4 and 4-6 months, respectively. Relative to an infection >2 years ago and controlling for vaccination, 63.6% (95% CI 46.9 to 75.0) and 29.1% (95% CI 3.8 to 43.1) greater protection against infection was estimated for an infection within the past 0-6, and 6-12 months, respectively. A fourth dose was associated with greater protection against asymptomatic infection than symptomatic infection, whilst prior infection independently provided more protection against symptomatic infection, particularly if the infection had occurred within the previous 6 months. Duration of PCR positivity was significantly lower for asymptomatic compared to symptomatic infection. Interpretation: Despite rapid waning of protection, vaccine boosters remain an important tool in responding to the dynamic COVID-19 landscape; boosting population immunity in advance of periods of anticipated pressure, such as surging infection rates or emerging variants of concern. Funding: UK Health Security Agency, Medical Research Council, NIHR HPRU Oxford, Bristol, and others.
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The COVID-19 pandemic saw unprecedented resources and funds driven into research for the development, and subsequent rapid distribution, of vaccines, diagnostics and directly acting antivirals (DAAs). DAAs have undeniably prevented progression and life-threatening conditions in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, there are concerns of antimicrobial resistance (AMR), antiviral resistance specifically, for DAAs. To preserve activity of DAAs for COVID-19 therapy, as well as detect possible mutations conferring resistance, antimicrobial stewardship and surveillance were rapidly implemented in England. This paper expands on the ubiquitous ongoing public health activities carried out in England, including epidemiologic, virologic and genomic surveillance, to support the stewardship of DAAs and assess the deployment, safety, effectiveness and resistance potential of these novel and repurposed therapeutics.
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COVID-19 , Humanos , COVID-19/epidemiologia , SARS-CoV-2 , Antibacterianos/uso terapêutico , Pandemias/prevenção & controle , Antivirais/uso terapêutico , Antivirais/farmacologia , Farmacorresistência Bacteriana , Inglaterra/epidemiologiaRESUMO
The 2022 global mpox outbreak raises questions about how this zoonotic disease established effective human-to-human transmission and its potential for further adaptation. The 2022 outbreak virus is related to an ongoing outbreak in Nigeria originally reported in 2017, but the evolutionary path linking the two remains unclear due to a lack of genomic data between 2018, when virus exportations from Nigeria were first recorded, and 2022, when the global mpox outbreak began. Here, 18 viral genomes obtained from patients across southern Nigeria in 2019-2020 reveal multiple lineages of monkeypox virus (MPXV) co-circulated in humans for several years before 2022, with progressive accumulation of mutations consistent with APOBEC3 activity over time. We identify Nigerian A.2 lineage isolates, confirming the lineage that has been multiply exported to North America independently of the 2022 outbreak originated in Nigeria, and that it has persisted by human-to-human transmission in Nigeria for more than 2 years before its latest exportation. Finally, we identify a lineage-defining APOBEC3-style mutation in all A.2 isolates that disrupts gene A46R, encoding a viral innate immune modulator. Collectively, our data demonstrate MPXV capacity for sustained diversification within humans, including mutations that may be consistent with established mechanisms of poxvirus adaptation.
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Monkeypox virus , Mpox , Humanos , Animais , Monkeypox virus/genética , Mpox/epidemiologia , Mpox/genética , Zoonoses , Surtos de Doenças , Evolução BiológicaRESUMO
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 challenge conventional nitrofurantoin susceptibility testing in clinical settings.
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Escherichia coli , Nitrofurantoína , Mutação , Nitrorredutases , OxigênioRESUMO
BACKGROUND: National Health Service (NHS) guidance for acute respiratory tract infections (RTIs) advocates self-care, encourages utilization of local pharmacies and recommends consulting general practitioners (GPs) primarily for the vulnerable or those with persistent symptoms. Coronavirus disease 2019 exerted substantial strain on the English NHS, affecting public access to primary care services. METHODS: For 3 years, public surveys assessed RTI incidences in the previous 12 months and associated health-seeking behaviours. Telephone surveys of 1676 respondents across England were conducted in March 2021 and 1663 respondents in March 2022. Findings were compared with a face-to-face baseline survey of 2022 respondents from March 2020. Key demographics were representative of the population. RESULTS: In 2021, the proportion of respondents who reported an RTI (51%) significantly declined from 2020 (70%, P < 0.05), then returned to pre-pandemic rates in 2022 (67%). Respondents reported more proactive symptom management in both 2021 and 2022 from 2020: there were greater reports of seeking over-the-counter treatments (55%, 55% vs. 35%, P < 0.05) and use of alternative remedies (38%, 38% vs. 21%, P < 0.05). 2022 observed a reduction in those who reported consulting their GP for their most recent RTI (15%) compared to 2021 (25%, P < 0.05) and 2020 (23%), which was not accounted for through greater consultation rates with other healthcare services. CONCLUSIONS: Public health bodies should consider how pandemic-related changes may have facilitated increased self-care for self-limiting infections such as RTIs. Resources and support must include safety-netting advice to safeguard against unintentional consequences of increased self-care.
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COVID-19 , Infecções Respiratórias , Humanos , Pandemias , Medicina Estatal , COVID-19/epidemiologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/terapia , Inglaterra/epidemiologia , Aceitação pelo Paciente de Cuidados de SaúdeRESUMO
The plans for a new antimicrobial utilization and resistance national surveillance programme, alongside the development of quality measures and methods to monitor unintended outcomes of antimicrobial stewardship and both public and professional behaviour interventions were published in 2013. Since then, England has published an annual surveillance report including outlining progress against the ambitions of the UK national action plans on antimicrobial resistance (2013 to 2018 and 2019 to 2024). A decade later we provide a brief update on progress so far, with a focus on key highlights from the latest report published in November 2022. We also provide our recommendations for areas of focus as we move into the next decade. From an initial focus on antibiotic consumption and resistance, the report now includes surveillance data for antifungals, antivirals (including novel agents, such as those targeting SARS-CoV-2) and antimalarials. Evaluation of key stewardship interventions including professional and public engagement initiatives are also reported, as well as progress against NHS England's (NHSE's) improvement measures.
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Anti-Infecciosos , COVID-19 , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , SARS-CoV-2 , Inglaterra/epidemiologiaRESUMO
OBJECTIVES: A global outbreak of mpox (monkeypox) has been ongoing since 2022, with most cases in the UK detected in gay, bisexual and other men who have sex with men (GBMSM). Asymptomatic and pauci-symptomatic mpox infection has been reported outside of the UK. We aimed to investigate whether mpox could be detected in specimens from GBMSM in England who were attending sexual health services (SHSs) for asymptomatic sexually transmitted infection screening. METHODS: Anonymised, residual clinical specimens from GBMSM undertaking routine asymptomatic screening for gonorrhoea (Neisseria gonorrhoeae (NG)) and chlamydia (Chlamydia trachomatis (CT)) infection were tested for the presence of mpox virus. Specimens were collected between 1 August and 7 October 2022 from three SHSs in high-mpox incidence areas in England. Testing was performed using a dual-clade, mpox virus-specific real-time PCR. RESULTS: During the collection period, 2927 clinical specimens (951 pharyngeal swabs, 1022 urine specimens and 954 rectal swabs) were obtained from 1159 GBMSM. Mpox virus was detected in four specimens from two participants who attended the same SHS at different times (the first during the week 8-12 of August, the second during the week 19-23 of September). One participant was positive in the urine specimen only, while the other tested positive at all three sites. CONCLUSIONS: A very low prevalence (2 of 1159, 0.17%) of mpox infection was detected in GBMSM attending SHS in England for asymptomatic NG/CT screening, suggesting that undetected infection in this population was unlikely to be a main driver of transmission. Confirmed mpox cases in the UK declined from over 1100 per month in June and July to 764 cumulatively during the collection period. These data give reassurance that the observed reduction in cases during the collection period was not due to undetected infection or changes in presentation among SHS attendees. Currently, there is insufficient evidence to support routine testing of asymptomatic GBMSM for mpox infection in England.
Assuntos
Infecções por Chlamydia , Gonorreia , Mpox , Minorias Sexuais e de Gênero , Masculino , Humanos , Homossexualidade Masculina , Monkeypox virus , Estudos Retrospectivos , Gonorreia/diagnóstico , Gonorreia/epidemiologia , Neisseria gonorrhoeae , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/epidemiologia , Infecções por Chlamydia/urina , Chlamydia trachomatis , Inglaterra/epidemiologiaRESUMO
Objective: To review the epidemiology of coagulase-negative staphylococci (CoNS) in England over the recent 12 year period. Methods: Laboratory-confirmed CoNS reported from sterile sites in patients in England to the UK Health Security Agency (UKHSA) between 2010 and 2021 were extracted from the national laboratory database and analysed. Results: Overall, 668â857 episodes of CoNS were reported. Unspeciated CoNS accounted for 56â% (374â228) of episodes, followed by Staphylococcus epidermidis (26â%; 174â050), S. hominis (6.5â%; 43â501) and S. capitis (3.9â%; 25â773). Unspeciated CoNS increased by 8.2â% (95â% CI, 7.1-9.3) annually between 2010 and 2016, then decreased annually by 6.4â% (95â% CI: -4.8 to -7.9) until 2021. Speciated CoNS increased by 47.6â% (95â% CI, 44.5-50.9) annually between 2010 and 2016 and increased annually by 8.9â% (95â% CI: 5.1 to 12.8) until 2021. Antimicrobial susceptibility profiles differed by species. Conclusions: Reports of CoNS from normally sterile body sites in patients in England increased between 2010 and 2016 and remained stable between 2017 and 2021. There has been a striking improvement in species-level identification of CoNS in recent years. Monitoring trends in CoNS epidemiology is crucial for development of observational and clinical intervention studies on individual species.