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In this study, 37% of 146,000 PCR-tested contacts of infected persons in England were positive for SARS-CoV-2. Transmission of the alpha variant from twice-vaccinated index patients was rarer than that from unvaccinated index patients (adjusted rate ratio with BNT162b2, 0.32). Vaccine protection waned over time and was more effective against the alpha strain than against the delta strain.

Key Points Whole-genome sequencing of bacterial isolates is becoming more and more widespread, paving the way for a transformation of many current procedures in clinical microbiology. Identifying the species of an isolate is currently a complex laboratory process. A few methods have already been proposed for doing this using the genome sequence, which could result in a re-evaluation of the bacterial species concept. Testing antibiotic resistance properties is often crucial for determining the appropriate treatment. As resistance is encoded by specific genes, this susceptibility assessment could be performed in silico using the genome sequence. The same is true for determining virulence properties of a strain, but with the difference that correlations between the genotype and phenotype is often more complex (involving several genes) than for resistance. However, association-mapping techniques can be used to detect such complex correlations, leading to a better understanding of pathogenicity. Several studies have already demonstrated the great potential of whole-genome sequencing in epidemiological investigations. These have so far been carried out after the course of an outbreak. In the future, with improving technology, this could be carried on an ongoing basis to detect epidemiological risks as they arise and react accordingly. Bacteria culturing is a pre-requirement even for whole-genome sequencing as it is currently carried out. This represents an important bottleneck as some bacteria are slow-growing and others cannot be cultured. Metagenomics approaches could provide a solution to this long-standing issue. This Review sets out the emerging potential of next-generation sequencing in the context of clinical microbiology. Using bacterial genome sequencing as an example, the authors discuss the options and challenges for species identification, testing for virulence and drug resistance and monitoring outbreaks. Whole-genome sequencing of bacteria has recently emerged as a cost-effective and convenient approach for addressing many microbiological questions. Here, we review the current status of clinical microbiology and how it has already begun to be transformed by using next-generation sequencing. We focus on three essential tasks: identifying the species of an isolate, testing its properties, such as resistance to antibiotics and virulence, and monitoring the emergence and spread of bacterial pathogens. We predict that the application of next-generation sequencing will soon be sufficiently fast, accurate and cheap to be used in routine clinical microbiology practice, where it could replace many complex current techniques with a single, more efficient workflow.

The effectiveness of the BNT162b2 and ChAdOx1 vaccines against new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections requires continuous re-evaluation, given the increasingly dominant B.1.617.2 (Delta) variant. In this study, we investigated the effectiveness of these vaccines in a large, community-based survey of randomly selected households across the United Kingdom. We found that the effectiveness of BNT162b2 and ChAdOx1 against infections (new polymerase chain reaction (PCR)-positive cases) with symptoms or high viral burden is reduced with the B.1.617.2 variant (absolute difference of 10–13% for BNT162b2 and 16% for ChAdOx1) compared to the B.1.1.7 (Alpha) variant. The effectiveness of two doses remains at least as great as protection afforded by prior natural infection. The dynamics of immunity after second doses differed significantly between BNT162b2 and ChAdOx1, with greater initial effectiveness against new PCR-positive cases but faster declines in protection against high viral burden and symptomatic infection with BNT162b2. There was no evidence that effectiveness varied by dosing interval, but protection was higher in vaccinated individuals after a prior infection and in younger adults. With B.1.617.2, infections occurring after two vaccinations had similar peak viral burden as those in unvaccinated individuals. SARS-CoV-2 vaccination still reduces new infections, but effectiveness and attenuation of peak viral burden are reduced with B.1.617.2. A large, community-based study in the United Kingdom indicates that the effectiveness of BNT162b2 and ChAdOx1 vaccines against SARS-CoV-2 infections with symptoms or high viral burden is reduced with the Delta variant compared to the Alpha variant.

Where does Clostridium difficile come from? In this report from the United Kingdom, of 1223 C. difficile isolates that were evaluated on whole-genome sequencing over a 3-year period, more than 45% were genetically distinct from all previous isolates. Most episodes of Clostridium difficile infection are believed to result from recent acquisition within a health care setting. Prevention efforts have therefore focused on symptomatic patients, their immediate environment, and judicious use of antimicrobial drugs. 1 , 2 Person-to-person transmission of C. difficile infection and surrounding contamination have been well documented. 2 – 5 However, there are multiple other potential sources, including patients with asymptomatic colonization 6 , 7 and sources in the wider environment, such as water, farm animals or pets, and food. 8 The contribution of cases acquired from these sources to the overall burden of disease is unclear, particularly with increasing reports of community-associated . . .

Candida auris is an emerging infectious agent with limited antimicrobial susceptibilities. An outbreak was identified in a neurosciences ICU in the United Kingdom and was linked to reusable temperature probes.

The effectiveness of COVID-19 vaccination in preventing new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in the general community is still unclear. Here, we used the Office for National Statistics COVID-19 Infection Survey—a large community-based survey of individuals living in randomly selected private households across the United Kingdom—to assess the effectiveness of the BNT162b2 (Pfizer–BioNTech) and ChAdOx1 nCoV-19 (Oxford–AstraZeneca; ChAdOx1) vaccines against any new SARS-CoV-2 PCR-positive tests, split according to self-reported symptoms, cycle threshold value (<30 versus ≥30; as a surrogate for viral load) and gene positivity pattern (compatible with B.1.1.7 or not). Using 1,945,071 real-time PCR results from nose and throat swabs taken from 383,812 participants between 1 December 2020 and 8 May 2021, we found that vaccination with the ChAdOx1 or BNT162b2 vaccines already reduced SARS-CoV-2 infections ≥21 d after the first dose (61% (95% confidence interval (CI) = 54–68%) versus 66% (95% CI = 60–71%), respectively), with greater reductions observed after a second dose (79% (95% CI = 65–88%) versus 80% (95% CI = 73–85%), respectively). The largest reductions were observed for symptomatic infections and/or infections with a higher viral burden. Overall, COVID-19 vaccination reduced the number of new SARS-CoV-2 infections, with the largest benefit received after two vaccinations and against symptomatic and high viral burden infections, and with no evidence of a difference between the BNT162b2 and ChAdOx1 vaccines. Results from the Office of National Statistics COVID-19 Infection Survey in the United Kingdom demonstrate that the ChAdOx1 nCoV-19 and BNT162b2 vaccines reduce the incidence of new SARS-CoV-2 infections by up to 65% with a single dose and up to 80% after two doses, with no significant differences in efficacy observed between the two vaccines.

Clostridium difficile infection (CDI) is a leading cause of antibiotic-associated diarrhoea and is endemic in hospitals, hindering the identification of sources and routes of transmission based on shared time and space alone. This may compromise rational control despite costly prevention strategies. This study aimed to investigate ward-based transmission of C. difficile, by subdividing outbreaks into distinct lineages defined by multi-locus sequence typing (MLST). All C. difficile toxin enzyme-immunoassay-positive and culture-positive samples over 2.5 y from a geographically defined population of ~600,000 persons underwent MLST. Sequence types (STs) were combined with admission and ward movement data from an integrated comprehensive healthcare system incorporating three hospitals (1,700 beds) providing all acute care for the defined geographical population. Networks of cases and potential transmission events were constructed for each ST. Potential infection sources for each case and transmission timescales were defined by prior ward-based contact with other cases sharing the same ST. From 1 September 2007 to 31 March 2010, there were means of 102 tests and 9.4 CDIs per 10,000 overnight stays in inpatients, and 238 tests and 15.7 CDIs per month in outpatients/primary care. In total, 1,276 C. difficile isolates of 69 STs were studied. From MLST, no more than 25% of cases could be linked to a potential ward-based inpatient source, ranging from 37% in renal/transplant, 29% in haematology/oncology, and 28% in acute/elderly medicine to 6% in specialist surgery. Most of the putative transmissions identified occurred shortly (≤ 1 wk) after the onset of symptoms (141/218, 65%), with few >8 wk (21/218, 10%). Most incubation periods were ≤ 4 wk (132/218, 61%), with few >12 wk (28/218, 13%). Allowing for persistent ward contamination following ward discharge of a CDI case did not increase the proportion of linked cases after allowing for random meeting of matched controls. In an endemic setting with well-implemented infection control measures, ward-based contact with symptomatic enzyme-immunoassay-positive patients cannot account for most new CDI cases.

With little evidence that failing to complete a prescribed antibiotic course contributes to antibiotic resistance, it’s time for policy makers, educators, and doctors to drop this message, argue Martin Llewelyn and colleagues

Combined genotyping/whole genome sequencing and epidemiological data suggest that in endemic settings only a minority of Clostridium difficile infection, CDI, is acquired from other cases. Asymptomatic patients are a potential source for many unexplained cases. We prospectively screened a cohort of medical inpatients in a UK teaching hospital for asymptomatic C. difficile carriage using stool culture. Electronic and questionnaire data were used to determine risk factors for asymptomatic carriage by logistic regression. Carriage isolates were compared with all hospital/community CDI cases from the same geographic region, from 12 months before the study to 3 months after, using whole genome sequencing and hospital admission data, assessing particularly for evidence of onward transmission from asymptomatic cases. Of 227 participants recruited, 132 provided ≥1 stool samples for testing. 18 participants were culture-positive for C. difficile, 14/132(11%) on their first sample. Independent risk factors for asymptomatic carriage were patient reported loose/frequent stool (but not meeting CDI criteria of ≥3 unformed stools in 24 hours), previous overnight hospital stay within 6 months, and steroid/immunosuppressant medication in the last 6 months (all p≤0.02). Surprisingly antibiotic exposure in the last 6 months was independently associated with decreased risk of carriage (p = 0.005). The same risk factors were identified excluding participants reporting frequent/loose stool. 13/18(72%) asymptomatically colonised patients carried toxigenic strains from common disease-causing lineages found in cases. Several plausible transmission events to asymptomatic carriers were identified, but in this relatively small study no clear evidence of onward transmission from an asymptomatic case was seen. Transmission events from any one asymptomatic carrier are likely to be relatively rare, but as asymptomatic carriage is common, it may still be an important source of CDI, which could be quantified in larger studies. Risk factors established for asymptomatic carriage may help identify patients for inclusion in such studies.

New approaches are urgently required to address increasing rates of gonorrhoea and the emergence and global spread of antibiotic-resistant Neisseria gonorrhoeae. We used whole-genome sequencing to study transmission and track resistance in N gonorrhoeae isolates. We did whole-genome sequencing of isolates obtained from samples collected from patients attending sexual health services in Brighton, UK, between Jan 1, 2011, and March 9, 2015. We also included isolates from other UK locations, historical isolates from Brighton, and previous data from a US study. Samples from symptomatic patients and asymptomatic sexual health screening underwent nucleic acid amplification testing; positive samples and all samples from symptomatic patients were cultured for N gonorrhoeae, and resulting isolates were whole-genome sequenced. Cefixime susceptibility testing was done in selected isolates by agar incorporation, and we used sequence data to determine multi-antigen sequence types and penA genotypes. We derived a transmission nomogram to determine the plausibility of direct or indirect transmission between any two cases depending on the time between samples: estimated mutation rates, plus diversity noted within patients across anatomical sites and probable transmission pairs, were used to fit a coalescent model to determine the number of single nucleotide polymorphisms expected. 1407 (98%) of 1437 Brighton isolates between Jan 1, 2011, and March 9, 2015 were successfully sequenced. We identified 1061 infections from 907 patients. 281 (26%) of these infections were indistinguishable (ie, differed by zero single nucleotide polymorphisms) from one or more previous cases, and 786 (74%) had evidence of a sampled direct or indirect Brighton source. We observed multiple related samples across geographical locations. Of 1273 infections in Brighton (including historical data), 225 (18%) were linked to another case elsewhere in the UK, and 115 (9%) to a case in the USA. Four lineages initially identified in Brighton could be linked to 70 USA sequences, including 61 from a lineage carrying the mosaic penA XXXIV allele, which is associated with reduced cefixime susceptibility. We present a whole-genome-sequencing-based tool for genomic contact tracing of N gonorrhoeae and demonstrate local, national, and international transmission. Whole-genome sequencing can be applied across geographical boundaries to investigate gonorrhoea transmission and to track antimicrobial resistance. Oxford National Institute for Health Research Health Protection Research Unit and Biomedical Research Centre.