Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 40
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
2.
Artigo em Inglês | MEDLINE | ID: mdl-32205351

RESUMO

Resistance to amoxicillin-clavulanate, a widely used beta-lactam/beta-lactamase inhibitor combination antibiotic, is rising globally, yet susceptibility testing remains challenging. To test whether whole-genome sequencing (WGS) could provide a more reliable assessment of susceptibility than traditional methods, we predicted resistance from WGS for 976 E. coli bloodstream infection isolates from Oxfordshire, UK, comparing against phenotypes from the BD Phoenix (calibrated against EUCAST guidelines). 339/976 (35%) isolates were amoxicillin-clavulanate resistant. Predictions based solely on beta-lactamase presence/absence performed poorly (sensitivity 23% (78/339)) but improved when genetic features associated with penicillinase hyper-production (e.g. promoter mutations, copy number estimates) were considered (sensitivity 82% (277/339); p<0.0001). Most discrepancies occurred in isolates with peri-breakpoint MICs. We investigated two potential causes; the phenotypic reference and the binary resistant/susceptible classification. We performed reference standard, replicated phenotyping in a random stratified subsample of 261/976 (27%) isolates using agar dilution, following both EUCAST and CLSI guidelines, which use different clavulanate concentrations. As well as disagreeing with each other, neither agar dilution phenotype aligned perfectly with genetic features. A random-effects model investigating associations between genetic features and MICs showed that some genetic features had small, variable and additive effects, resulting in variable resistance classification. Using model fixed-effects to predict MICs for the non-agar dilution isolates, predicted MICs were in essential agreement (±1 doubling dilution) with observed (BD Phoenix) MICs for 691/715 (97%) isolates. This suggests amoxicillin-clavulanate resistance in E. coli is quantitative, rather than qualitative, explaining the poorly reproducible binary (resistant/susceptible) phenotypes and suboptimal concordance between different phenotypic methods and with WGS-based predictions.

3.
J Card Surg ; 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32058604

RESUMO

We report a case of culture-negative aortic valve endocarditis secondary to Tropheryma whipplei infection. Our patient underwent aortic valve replacement after 4 weeks of antibiotic therapy with persistently negative blood culture results. Despite a technically uneventful operation, the patient showed continued sepsis and was unresponsive to a broad-spectrum of antibiotic therapy with subsequent multiorgan failure. He died on the 5th postoperative day, and diagnosis was established at postmortem examination. In this case report, we discuss the diagnosis and treatment of a rare type of endocarditis caused by T. whipplei.

4.
J Infect ; 2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32092386

RESUMO

BACKGROUND: Human metapneumovirus (HMPV) infection causes a spectrum of respiratory tract disease, and may be a significant pathogen in the context of immunocompromise. Here, we report direct-from-sample metagenomic sequencing of HMPV using Oxford Nanopore Technology. METHODS: We applied this sequencing approach to 25 respiratory samples that had been submitted to a clinical diagnostic laboratory in a UK teaching hospital. These samples represented 13 patients under the care of a haematology unit over a 20-day period in Spring 2019 (two sampled twice), and ten other patients elsewhere in the hospital between 2017-2019. RESULTS: We generated HMPV reads from 20/25 samples (sensitivity 80% compared to routine diagnostic testing) and retrieved complete HMPV genomes from 15/20 of these. Consensus sequences from Nanopore data were identical to those generated by Illumina, and represented HMPV genomes from two distinct sublineages, A2b and B2. Sequences from ten haematology patients formed a unique genetic group in the A2b sublineage, not previously reported in the UK. Among these, eight HMPV genomes formed a cluster (differing by ≤3 SNPs), likely to reflect nosocomial transmission, while two others were more distantly related and may represent independent introductions to the haematology unit. CONCLUSION: Nanopore metagenomic sequencing can be used to diagnose HMPV infection, although more work is required to optimise sensitivity. Improvements in the use of metagenomic sequencing, particularly for respiratory viruses, could contribute to antimicrobial stewardship. Generation of full genome sequences can be used to support or rule out nosocomial transmission, and contribute to improving infection prevention and control practices.

5.
J Clin Microbiol ; 58(1)2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31666364

RESUMO

Influenza is a major global public health threat as a result of its highly pathogenic variants, large zoonotic reservoir, and pandemic potential. Metagenomic viral sequencing offers the potential for a diagnostic test for influenza virus which also provides insights on transmission, evolution, and drug resistance and simultaneously detects other viruses. We therefore set out to apply the Oxford Nanopore Technologies sequencing method to metagenomic sequencing of respiratory samples. We generated influenza virus reads down to a limit of detection of 102 to 103 genome copies/ml in pooled samples, observing a strong relationship between the viral titer and the proportion of influenza virus reads (P = 4.7 × 10-5). Applying our methods to clinical throat swabs, we generated influenza virus reads for 27/27 samples with mid-to-high viral titers (cycle threshold [CT ] values, <30) and 6/13 samples with low viral titers (CT values, 30 to 40). No false-positive reads were generated from 10 influenza virus-negative samples. Thus, Nanopore sequencing operated with 83% sensitivity (95% confidence interval [CI], 67 to 93%) and 100% specificity (95% CI, 69 to 100%) compared to the current diagnostic standard. Coverage of full-length virus was dependent on sample composition, being negatively influenced by increased host and bacterial reads. However, at high influenza virus titers, we were able to reconstruct >99% complete sequences for all eight gene segments. We also detected a human coronavirus coinfection in one clinical sample. While further optimization is required to improve sensitivity, this approach shows promise for the Nanopore platform to be used in the diagnosis and genetic analysis of influenza virus and other respiratory viruses.

6.
mBio ; 10(3)2019 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-31239374

RESUMO

HBsAg and HBeAg have gained traction as biomarkers of control and clearance during chronic hepatitis B virus infection (CHB). Improved understanding of the clearance correlates of these proteins could help inform improvements in patient-stratified care and advance insights into the underlying mechanisms of disease control, thus underpinning new cure strategies. We collected electronic clinical data via an electronic pipeline supported by the National Institute for Health Research Health Informatics Collaborative (NIHR HIC), adopting an unbiased approach to the generation of a robust longitudinal data set for adults testing HBsAg positive from a large UK teaching hospital over a 6-year period (2011 to 2016 inclusive). Of 553 individuals with CHB, longitudinal data were available for 319, representing >107,000 weeks of clinical follow-up. Among these 319 individuals, 13 (4%) cleared HBsAg completely. Among these 13, the HBsAg clearance rate in individuals on nucleos(t)ide analogue (NA) therapy (n = 4 [31%]; median clearance time,150 weeks) was similar to that in individuals not on NA therapy (n = 9 [69%]; median clearance time, 157 weeks). Those who cleared HBsAg were significantly older and less likely to be on NA therapy than nonclearers (P = 0.003 and P = 0.001, respectively). Chinese ethnicity was associated with HBeAg positivity (P = 0.025). HBeAg clearance occurred in individuals both on NA therapy (n = 24; median time, 49 weeks) and off NA therapy (n = 19; median time, 52 weeks). Improved insights into the dynamics of these biomarkers can underpin better prognostication and patient-stratified care. Our systematized approach to data collection paves the way for scaling up efforts to harness clinical data to address research questions and support improvements in clinical care.IMPORTANCE Advances in the diagnosis, monitoring, and treatment of hepatitis B virus (HBV) infection are urgently required if we are to meet international targets for elimination by the year 2030. Here we demonstrate how routine clinical data can be harnessed through an unbiased electronic pipeline, showcasing the significant potential for amassing large clinical data sets that can help to inform advances in patient care and provide insights that may help to inform new cure strategies. Our cohort from a large UK hospital includes adults from diverse ethnic groups that have previously been underrepresented in the literature. By tracking two protein biomarkers that are used to monitor chronic HBV infection, we provide new insights into the timelines of HBV clearance, both on and off treatment. These results contribute to improvements in individualized clinical care and may provide important clues into the immune events that underpin disease control.


Assuntos
Antígenos de Superfície da Hepatite B/sangue , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/sangue , Adolescente , Adulto , Idoso , Antivirais/uso terapêutico , Biomarcadores/sangue , Criança , Estudos de Coortes , Feminino , Vírus da Hepatite B , Hepatite B Crônica/tratamento farmacológico , Hospitais/estatística & dados numéricos , Humanos , Estudos Longitudinais , Masculino , Informática Médica , Pessoa de Meia-Idade , Reino Unido , Adulto Jovem
7.
J Infect ; 78(6): 461-467, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30965067

RESUMO

BACKGROUND: Due to paucity of evidence to guide management of allogeneic haematopoietic stem cell transplantation (allo-HSCT) patients with respiratory syncytial virus (RSV) infections national and international guidelines make disparate recommendations. METHODS: The outcomes of allo-HSCT recipients with RSV infection between 2015 and 2017 were assessed using the following treatment stratification; upper respiratory tract infections (URTI) being actively monitored and lower respiratory tract infections (LRTI) treated with short courses of oral ribavirin combined with intravenous immunoglobulin (IVIG, 2 g/kg). RESULTS: During the study period 49 RSV episodes were diagnosed (47% URTI and 53% LRTI). All patients with URTI recovered without pharmacological intervention. Progression from URTI to LRTI occurred in 15%. Treatment with oral ribavirin given until significant symptomatic improvement (median 7 days [3-12]) and IVIG for LRTI was generally well tolerated. RSV-attributable mortality was low (2%). CONCLUSIONS: In this cohort study, we demonstrate that active monitoring of allo-HSCT patients with RSV in the absence of LRTI was only associated with progression to LRTI in 15% of our patients and therefore appears to be a safe approach. Short course oral ribavirin in combination with IVIG was effective and well-tolerated for LRTI making it a practical alternative to aerosolised ribavirin. This approach was beneficial in reducing hospitalisation, saving nursing times and by using oral as opposed to nebulised ribavirin.

9.
BMC Med ; 17(1): 43, 2019 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-30786896

RESUMO

BACKGROUND: Sustainable Development Goals set a challenge for the elimination of hepatitis B virus (HBV) infection as a public health concern by the year 2030. Deployment of a robust prophylactic vaccine and enhanced interventions for prevention of mother to child transmission (PMTCT) are cornerstones of elimination strategy. However, in light of the estimated global burden of 290 million cases, enhanced efforts are required to underpin optimisation of public health strategy. Robust analysis of population epidemiology is particularly crucial for populations in Africa made vulnerable by HIV co-infection, poverty, stigma and poor access to prevention, diagnosis and treatment. METHODS: We here set out to evaluate the current and future role of HBV vaccination and PMTCT as tools for elimination. We first investigated the current impact of paediatric vaccination in a cohort of children with and without HIV infection in Kimberley, South Africa. Second, we used these data to inform a new parsimonious model to simulate the ongoing impact of preventive interventions. By applying these two approaches in parallel, we are able to determine both the current impact of interventions, and the future projected outcome of ongoing preventive strategies over time. RESULTS: Existing efforts have been successful in reducing paediatric prevalence of HBV infection in this setting to < 1%, demonstrating the success of the existing vaccine campaign. Our model predicts that, if consistently deployed, combination efforts of vaccination and PMTCT can significantly reduce population prevalence (HBsAg) by 2030, such that a major public health impact is possible even without achieving elimination. However, the prevalence of HBV e-antigen (HBeAg)-positive carriers will decline more slowly, representing a persistent population reservoir. We show that HIV co-infection significantly reduces titres of vaccine-mediated antibody, but has a relatively minor role in influencing the projected time to elimination. Our model can also be applied to other settings in order to predict impact and time to elimination based on specific interventions. CONCLUSIONS: Through extensive deployment of preventive strategies for HBV, significant positive public health impact is possible, although time to HBV elimination as a public health concern is likely to be substantially longer than that proposed by current goals.


Assuntos
Coinfecção/epidemiologia , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Vacinas contra Hepatite B/uso terapêutico , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Adolescente , Adulto , Criança , Estudos de Coortes , Feminino , Vacinas contra Hepatite B/farmacologia , Humanos , Pessoa de Meia-Idade , Adulto Jovem
11.
J Med Microbiol ; 68(3): 395-397, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30663952

RESUMO

PURPOSE: Polymerase chain reaction (PCR) is increasingly being used to detect enteric pathogens and is currently NICE's recommended practice. We wished to evaluate the performance characteristics of PCR for the detection of salmonella in consecutive stool samples in a real-world setting, compared to the gold standard of enrichment culture. METHODOLOGY: We performed a prospective study over 9 months in which the PCR and culture results for salmonella were scrutinized for all stool samples sent to the laboratory. All stool samples underwent selenite enrichment culture for salmonella with confirmation being obtained using the API 10S and serotyping. Samples also underwent PCR using the BD MAX Enteric Bacterial Panel. The sensitivity and specificity of PCR in detecting salmonella were compared to those of enrichment culture. RESULTS: Six thousand three hundred and seventy-two stool culture and PCR pairs from 5619 patients were analysed. The prevalence of salmonella was found to be 1.2 %. The sensitivity, specificity, positive predictive value and negative predictive value of PCR versus culture were 89 % (67/75), 99.8 % (6286/6297), 86 % (67/78) and 99.9 % (6286/6294), respectively. CONCLUSION: Enrichment culture is significantly more sensitive than PCR using the BD MAX Enteric Bacterial Panel for detecting salmonella in stool. Where PCR testing is used for the detection of enteric pathogens, we recommend that enrichment culture for salmonella be continued in parallel, unless the PCR method is shown to be at least as sensitive as culture.


Assuntos
Técnicas Bacteriológicas , Fezes/microbiologia , Reação em Cadeia da Polimerase , Salmonella/isolamento & purificação , Diarreia/microbiologia , Humanos , Técnicas de Diagnóstico Molecular , Valor Preditivo dos Testes , Estudos Prospectivos , Salmonella/genética , Salmonella/crescimento & desenvolvimento , Sensibilidade e Especificidade
12.
PLoS One ; 14(1): e0210407, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30615688

RESUMO

Multiplex Serology is a high-throughput technology developed to simultaneously measure specific serum antibodies against multiple pathogens in one reaction vessel. Serological assays for hepatitis B (HBV) and C (HCV) viruses, human T-lymphotropic virus 1 (HTLV-1) and the protozoan parasite Toxoplasma gondii (T. gondii) were developed and validated against established reference assays. For each pathogen, between 3 and 5 specific antigens were recombinantly expressed as GST-tag fusion proteins in Escherichia coli and tested in Monoplex Serology, i.e. assays restricted to the antigens from one particular pathogen. For each of the four pathogen-specific Monoplex assays, overall seropositivity was defined using two pathogen-specific antigens. In the case of HBV Monoplex Serology, the detection of past natural HBV infection was validated based on two independent reference panels resulting in sensitivities of 92.3% and 93.0%, and specificities of 100% in both panels. Validation of HCV and HTLV-1 Monoplex Serology resulted in sensitivities of 98.0% and 95.0%, and specificities of 96.2% and 100.0%, respectively. The Monoplex Serology assay for T. gondii was validated with a sensitivity of 91.2% and specificity of 92.0%. The developed Monoplex Serology assays largely retained their characteristics when they were included in a multiplex panel (i.e. Multiplex Serology), containing additional antigens from a broad range of other pathogens. Thus HBV, HCV, HTLV-1 and T. gondii Monoplex Serology assays can efficiently be incorporated into Multiplex Serology panels tailored for application in seroepidemiological studies.


Assuntos
Anticorpos Antivirais/sangue , Antígenos/imunologia , Infecções por HTLV-I/sangue , Hepatite B/sangue , Hepatite C/sangue , Testes Sorológicos/métodos , Toxoplasmose/sangue , Anticorpos Antivirais/imunologia , Antígenos de Protozoários/imunologia , Antígenos Virais/imunologia , Infecções por HTLV-I/imunologia , Infecções por HTLV-I/virologia , Hepacivirus/imunologia , Hepatite B/imunologia , Hepatite B/virologia , Vírus da Hepatite B/imunologia , Hepatite C/imunologia , Hepatite C/virologia , Ensaios de Triagem em Larga Escala , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Humanos , Estudos Soroepidemiológicos , Toxoplasma/imunologia , Toxoplasmose/imunologia , Toxoplasmose/parasitologia
13.
Artigo em Inglês | MEDLINE | ID: mdl-30397069

RESUMO

Mycobacterium abscessus is emerging as an important pathogen in chronic lung diseases, with concern regarding patient-to-patient transmission. The recent introduction of routine whole-genome sequencing (WGS) as a replacement for existing reference techniques in England provides an opportunity to characterize the genetic determinants of resistance. We conducted a systematic review to catalogue all known resistance-determining mutations. This knowledge was used to construct a predictive algorithm based on mutations in the erm(41) and rrl genes which was tested on a collection of 203 sequentially acquired clinical isolates for which there were paired genotype/phenotype data. A search for novel resistance-determining mutations was conducted using a heuristic algorithm. The sensitivity of existing knowledge for predicting resistance in clarithromycin was 95% (95% confidence interval [CI], 89 to 98%), and the specificity was 66% (95% CI, 54 to 76%). The subspecies alone was a poor predictor of resistance to clarithromycin. Eight potential new resistance-conferring single nucleotide polymorphisms (SNPs) were identified. WGS demonstrated probable resistance-determining SNPs in regions that the NTM-DR line probe cannot detect. These mutations are potentially clinically important, as they all occurred in samples that were predicted to be inducibly resistant and for which a macrolide would therefore currently be indicated. We were unable to explain all resistance, raising the possibility of the involvement of other as yet unidentified genes.


Assuntos
Antibacterianos/farmacologia , Claritromicina/farmacologia , Genoma Bacteriano/genética , Mycobacterium abscessus/efeitos dos fármacos , Mycobacterium abscessus/genética , Humanos , Metiltransferases/genética , Testes de Sensibilidade Microbiana , Infecções por Micobactéria não Tuberculosa/tratamento farmacológico , Infecções por Micobactéria não Tuberculosa/microbiologia , Polimorfismo de Nucleotídeo Único/genética , RNA Ribossômico 23S/genética , Sequenciamento Completo do Genoma
14.
N Engl J Med ; 379(14): 1322-1331, 2018 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-30281988

RESUMO

BACKGROUND: Candida auris is an emerging and multidrug-resistant pathogen. Here we report the epidemiology of a hospital outbreak of C. auris colonization and infection. METHODS: After identification of a cluster of C. auris infections in the neurosciences intensive care unit (ICU) of the Oxford University Hospitals, United Kingdom, we instituted an intensive patient and environmental screening program and package of interventions. Multivariable logistic regression was used to identify predictors of C. auris colonization and infection. Isolates from patients and from the environment were analyzed by whole-genome sequencing. RESULTS: A total of 70 patients were identified as being colonized or infected with C. auris between February 2, 2015, and August 31, 2017; of these patients, 66 (94%) had been admitted to the neurosciences ICU before diagnosis. Invasive C. auris infections developed in 7 patients. When length of stay in the neurosciences ICU and patient vital signs and laboratory results were controlled for, the predictors of C. auris colonization or infection included the use of reusable skin-surface axillary temperature probes (multivariable odds ratio, 6.80; 95% confidence interval [CI], 2.96 to 15.63; P<0.001) and systemic fluconazole exposure (multivariable odds ratio, 10.34; 95% CI, 1.64 to 65.18; P=0.01). C. auris was rarely detected in the general environment. However, it was detected in isolates from reusable equipment, including multiple axillary skin-surface temperature probes. Despite a bundle of infection-control interventions, the incidence of new cases was reduced only after removal of the temperature probes. All outbreak sequences formed a single genetic cluster within the C. auris South African clade. The sequenced isolates from reusable equipment were genetically related to isolates from the patients. CONCLUSIONS: The transmission of C. auris in this hospital outbreak was found to be linked to reusable axillary temperature probes, indicating that this emerging pathogen can persist in the environment and be transmitted in health care settings. (Funded by the National Institute for Health Research Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at Oxford University and others.).


Assuntos
Candida , Candidíase/epidemiologia , Infecção Hospitalar/epidemiologia , Surtos de Doenças , Contaminação de Equipamentos , Reutilização de Equipamento , Controle de Infecções/métodos , Unidades de Terapia Intensiva , Termômetros/microbiologia , Adulto , Candida/genética , Candida/isolamento & purificação , Candidíase/mortalidade , Candidíase/transmissão , Estudos de Casos e Controles , Infecção Hospitalar/mortalidade , Infecção Hospitalar/transmissão , Feminino , Departamentos Hospitalares , Humanos , Incidência , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Análise Multivariada , Neurologia , Filogenia , Fatores de Risco , Reino Unido/epidemiologia
15.
BMC Infect Dis ; 18(1): 461, 2018 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-30217169

RESUMO

BACKGROUND: As direct acting antiviral (DAA) therapy is progressively rolled out for patients with hepatitis C virus (HCV) infection, careful scrutiny of HCV epidemiology, diagnostic testing, and access to care is crucial to underpin improvements in delivery of treatment, with the ultimate goal of elimination. METHODS: We retrospectively studied microbiology records from a large UK teaching hospital in order to compare the performance of HCV screening and diagnostic tests (antibody, antigen and HCV RNA detection). Having described a local cohort of adults with active HCV infection, we investigated the proportion who attended hospital appointments, were prescribed direct acting antiviral (DAA) therapy, and cleared HCV RNA following treatment. RESULTS: Over a total time period of 33 months between 2013 and 2016, we tested 38,509 individuals for HCV infection and confirmed a new diagnosis of active HCV infection (HCV-Ag + and/or HCV RNA+) in 353 (positive rate 0.9%). Our in-house HCV-Ab screening test had a positive predictive value of 87% compared to repeat HCV-Ab testing in a reference laboratory, highlighting the potential for false positives to arise using this test. HCV-Ag had 100% positive predictive value compared to detection of HCV RNA. There was a strong correlation between quantitative HCV-Ag and HCV RNA viral load (p < 0.0001). Among the cases of infection, genotype-1 and genotype-3 predominated, the median age was 37 years, 84% were male, and 36% were in prison. Hepatology review was provided in 39%, and 22% received treatment. Among those who received DAA therapy with 12 weeks of follow-up, 93% achieved a sustained virologic response (SVR12). CONCLUSIONS: HCV-Ag performs well as a diagnostic test compared to PCR for HCV RNA. Active HCV infection is over-represented among men and in the prison population. DAA therapy is successful in those who receive it, but a minority of patients with a diagnosis of HCV infection access clinical care. Enhanced efforts are required to provide linkage to clinical care within high risk populations.


Assuntos
Hepatite C/diagnóstico , Adulto , Antivirais/uso terapêutico , Estudos de Coortes , Feminino , Genótipo , Hepacivirus/genética , Hepacivirus/imunologia , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Hepatite C/virologia , Anticorpos Anti-Hepatite C/sangue , Hospitais de Ensino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Estudos Retrospectivos , Resposta Viral Sustentada , Reino Unido/epidemiologia
16.
Lancet Infect Dis ; 18(10): 1138-1149, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30126643

RESUMO

BACKGROUND: Escherichia coli bloodstream infections are increasing in the UK and internationally. The evidence base to guide interventions against this major public health concern is small. We aimed to investigate possible drivers of changes in the incidence of E coli bloodstream infection and antibiotic susceptibilities in Oxfordshire, UK, over the past two decades, while stratifying for time since hospital exposure. METHODS: In this observational study, we used all available data on E coli bloodstream infections and E coli urinary tract infections (UTIs) from one UK region (Oxfordshire) using anonymised linked microbiological data and hospital electronic health records from the Infections in Oxfordshire Research Database (IORD). We estimated the incidence of infections across a two decade period and the annual incidence rate ratio (aIRR) in 2016. We modelled the data using negative binomial regression on the basis of microbiological, clinical, and health-care-exposure risk factors. We investigated infection severity, 30-day all-cause mortality, and community and hospital amoxicillin plus clavulanic acid (co-amoxiclav) use to estimate changes in bacterial virulence and the effect of antimicrobial resistance on incidence. FINDINGS: From Jan 1, 1998, to Dec 31, 2016, 5706 E coli bloodstream infections occurred in 5215 patients, and 228 376 E coli UTIs occurred in 137 075 patients. 1365 (24%) E coli bloodstream infections were nosocomial (onset >48 h after hospital admission), 1132 (20%) were quasi-nosocomial (≤30 days after discharge), 1346 (24%) were quasi-community (31-365 days after discharge), and 1863 (33%) were community (>365 days after hospital discharge). The overall incidence increased year on year (aIRR 1·06, 95% CI 1·05-1·06). In 2016, 212 (41%) of 515 E coli bloodstream infections and 3921 (28%) of 13 792 E coli UTIs were co-amoxiclav resistant. Increases in E coli bloodstream infections were driven by increases in community (aIRR 1·10, 95% CI 1·07-1·13; p<0·0001) and quasi-community (aIRR 1·08, 1·07-1·10; p<0·0001) cases. 30-day mortality associated with E coli bloodstream infection decreased over time in the nosocomial (adjusted rate ratio [RR] 0·98, 95% CI 0·96-1·00; p=0·03) group, and remained stable in the quasi-nosocomial (adjusted RR 0·98, 0·95-1·00; p=0·06), quasi-community (adjusted RR 0·99, 0·96-1·01; p=0·32), and community (adjusted RR 0·99, 0·96-1·01; p=0·21) groups. Mortality was, however, substantial at 14-25% across all hospital-exposure groups. Co-amoxiclav-resistant E coli bloodstream infections increased in all groups across the study period (by 11-18% per year, significantly faster than co-amoxiclav-susceptible E coli bloodstream infections; pheterogeneity<0·0001), as did co-amoxiclav-resistant E coli UTIs (by 14-29% per year; pheterogeneity<0·0001). Previous year co-amoxiclav use in primary-care facilities was associated with increased subsequent year community co-amoxiclav-resistant E coli UTIs (p=0·003). INTERPRETATION: Increases in E coli bloodstream infections in Oxfordshire are primarily community associated, with substantial co-amoxiclav resistance; nevertheless, we found little or no change in mortality. Focusing interventions on primary care facilities, particularly those with high co-amoxiclav use, could be effective in reducing the incidence of co-amoxiclav-resistant E coli bloodstream infections, in this region and more generally. FUNDING: National Institute for Health Research.


Assuntos
Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Antibacterianos/uso terapêutico , Bacteriemia/epidemiologia , Registros Eletrônicos de Saúde , Infecções por Escherichia coli/epidemiologia , Infecções Urinárias/epidemiologia , Bacteriemia/tratamento farmacológico , Bacteriemia/mortalidade , Farmacorresistência Bacteriana , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/mortalidade , Humanos , Incidência , Fatores de Tempo , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/mortalidade
17.
BMC Res Notes ; 11(1): 120, 2018 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-29426368

RESUMO

OBJECTIVES: There is increasing interest in the use of metagenomic (next generation sequencing, NGS) approaches for diagnosis of infection. We undertook a pilot study to screen samples submitted to a diagnostic microbiology laboratory in a UK teaching hospital using Illumina HiSeq. In the short-term, this small dataset provides insights into the virome of human respiratory and cerebrospinal fluid (CSF) samples. In the longer term, assimilating metagenomic data sets of this nature can inform optimization of laboratory and bioinformatic methods, and develop foundations for the interpretation of results in a clinical context. The project underpins a larger ongoing effort to develop NGS pipelines for diagnostic use. DATA DESCRIPTION: Our data comprise a complete metagenomic dataset from 20 independent samples (10 CSF and 10 respiratory) submitted to the clinical microbiology laboratory for a large UK teaching hospital (Oxford University Hospitals NHS Foundation Trust). Sequences have been uploaded to the European Nucleotide Archive and are also presented as Krona plots through which the data can be interactively visualized. In the longer term, further optimization is required to better define sensitivity and specificity of this approach to clinical samples.


Assuntos
Líquido Cefalorraquidiano/virologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Metagenômica/métodos , Análise de Sequência de DNA/métodos , Escarro/virologia , Humanos , Projetos Piloto
18.
Clin Microbiol Rev ; 31(1)2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29142078

RESUMO

The emerging pathogen Candida auris has been associated with nosocomial outbreaks on five continents. Genetic analysis indicates the simultaneous emergence of separate clades of this organism in different geographical locations. Invasive infection and colonization have been detected predominantly in patients in high-dependency settings and have garnered attention due to variable antifungal resistance profiles and transmission within units instituting a range of infection prevention and control measures. Issues with the identification of C. auris using both phenotypic and molecular techniques have raised concerns about detecting the true scale of the problem. This review considers the literature available on C. auris and highlights the key unknowns, which will provide direction for further work in this field.


Assuntos
Candida , Candidíase/diagnóstico , Candidíase/microbiologia , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/microbiologia , Farmacorresistência Fúngica , Humanos
19.
Int J STD AIDS ; 28(7): 667-671, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-27405582

RESUMO

The sexual health service in Oxford introduced gonorrhoea nucleic amplification acid testing using the BD Viper XTR™ System. For practical reasons, a confirmatory nucleic amplification acid testing using a different platform was not used initially. Following the introduction of nucleic amplification acid testing, the rates of gonorrhoea increased threefold. Concerns were raised that this increase represented an outbreak. A retrospective review of cases over six months suggested that there may have been a number of false-positive results. A prospective study was then undertaken over six months, where all gonorrhoea positive samples were sent for confirmatory testing. This evaluation of all gonorrhoea cases in an English county found that the overall presumptive false-positive rates for gonorrhoea nucleic amplification acid testing using BD Viper XTR™ in our population are significant at 27% of female samples, 13.2% of heterosexual male samples, 3.5% of anogenital multiple site men who have sex with men samples and 62.8% of pharyngeal only men who have sex with men samples. The data demonstrate the need for confirmatory testing using a second nucleic acid target, as per BASHH/Public Health England guidelines, especially in low-prevalence settings and extragenital sites, due to cross-reactivity with commensal Neisseria species and low positive predictive values.


Assuntos
Surtos de Doenças , Gonorreia/diagnóstico , Neisseria gonorrhoeae/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , Adulto , Inglaterra/epidemiologia , Feminino , Gonorreia/epidemiologia , Humanos , Ilusões , Masculino , Neisseria gonorrhoeae/isolamento & purificação , Prevalência , Estudos Prospectivos , Melhoria de Qualidade , Comportamento Sexual
20.
Int J STD AIDS ; 28(4): 357-361, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27150360

RESUMO

Trichomonas vaginalis (TV) rates in women are increasing and many are asymptomatic. Nucleic acid amplification tests (NAATs) are becoming the 'gold standard' for diagnosis. We aimed to establish our asymptomatic TV rates by testing all women attending Oxfordshire's Sexual Health service, regardless of symptoms, using the BD ProbeTec™ TV Qx NAATs (BDQx). During BDQx's verification process, the sensitivity and specificity were calculated using results of 220 endocervical samples from symptomatic women, compared with culture. BDQx was subsequently implemented and prospectively evaluated over 6 months in female attendees. Wet mount microscopy was also performed in symptomatics. Demographic and clinical characteristics of those diagnosed were analysed. From 220 samples tested by BDQx and culture: 5 were positive on both and one solely using BDQx, giving a sensitivity and specificity of 100% and 99.53%, respectively. In the prospective cohort, of 5775 BDQx tests, 33 (0.57%) were positive. 11/33 (33%) patients were asymptomatic. All patients diagnosed had risk factors: age >25 years (85%), residence in a deprived area (79%) and black ethnicity (21%). Despite BDQx being highly sensitive and specific, with our low TV prevalence universal screening may not be justified. Targeted screening using local demographic data merits further investigation.


Assuntos
Tricomoníase/diagnóstico , Trichomonas vaginalis/isolamento & purificação , Adulto , Doenças Assintomáticas , Colo do Útero , Demografia , Feminino , Humanos , Técnicas de Amplificação de Ácido Nucleico , Prevalência , Estudos Prospectivos , Kit de Reagentes para Diagnóstico , Sensibilidade e Especificidade , Tricomoníase/epidemiologia , Tricomoníase/parasitologia , Trichomonas vaginalis/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA