Soft Tissue Infection of Immunocompetent Man with Cat-Derived Globicatella Species.

We report a novel Globicatella species causing extensive soft tissue infection in a man bitten by a stray domestic cat in the United Kingdom. We identified this bacterium by 16S rRNA gene sequencing, whole-genome sequencing, and biochemical profiling and determined antimicrobial drug susceptibility.

A2B-COVID: A Tool for Rapidly Evaluating Potential SARS-CoV-2 Transmission Events.

Identifying linked cases of infection is a critical component of the public health response to viral infectious diseases. In a clinical context, there is a need to make rapid assessments of whether cases of infection have arrived independently onto a ward, or are potentially linked via direct transmission. Viral genome sequence data are of great value in making these assessments, but are often not the only form of data available. Here, we describe A2B-COVID, a method for the rapid identification of potentially linked cases of COVID-19 infection designed for clinical settings. Our method combines knowledge about infection dynamics, data describing the movements of individuals, and evolutionary analysis of genome sequences to assess whether data collected from cases of infection are consistent or inconsistent with linkage via direct transmission. A retrospective analysis of data from two wards at Cambridge University Hospitals NHS Foundation Trust during the first wave of the pandemic showed qualitatively different patterns of linkage between cases on designated COVID-19 and non-COVID-19 wards. The subsequent real-time application of our method to data from the second epidemic wave highlights its value for monitoring cases of infection in a clinical context.

Impact of penicillin allergy labels on surgical site infections in a large UK cohort of gastrointestinal surgery patients.

Objectives: Studies in the USA, Canada and France have reported higher surgical site infection (SSI) risk in patients with a penicillin allergy label (PAL). Here, we investigate the association between PALs and SSI in the UK, a country with distinct epidemiology of infecting pathogens and range of antimicrobial regimens in routine use. Methods: Electronic health records and national SSI surveillance data were collated for a retrospective cohort of gastrointestinal surgery patients at Cambridge University Hospitals NHS Foundation Trust from 1 January 2015 to 31 December 2021. Univariable and multivariable logistic regression were used to examine the effects of PALs and the use of non-ß-lactam-based prophylaxis on likelihood of SSI, 30 day post-operative mortality, 7 day post-operative acute kidney injury and 60 day post-operative infection/colonization with antimicrobial-resistant bacteria or Clostridioides difficile. Results: Our data comprised 3644 patients and 4085 operations; 461 were undertaken in the presence of PALs (11.3%). SSI was detected after 435/4085 (10.7%) operations. Neither the presence of PALs, nor the use of non-ß-lactam-based prophylaxis were found to be associated with SSI: adjusted OR (aOR) 0.90 (95% CI 0.65-1.25) and 1.20 (0.88-1.62), respectively. PALs were independently associated with increased odds of newly identified MRSA infection/colonization in the 60 days after surgery: aOR 2.71 (95% CI 1.13-6.49). Negative association was observed for newly identified infection/colonization with third-generation cephalosporin-resistant Gram-negative bacteria: aOR 0.38 (95% CI 0.16-0.89). Conclusions: No evidence was found for an association between PALs and the likelihood of SSI in this large UK cohort, suggesting significant international variation in the impact of PALs on surgical patients.

Characterizing Antibiotic Allergy Labels in a Large UK Hospital Population to Inform Antimicrobial Stewardship and Delabeling Assessment Strategy.

BACKGROUND: Antibiotic allergy labels are important barriers to treatment and antimicrobial stewardship, but their prevalence in UK hospitals is poorly described. OBJECTIVE: To ascertain the prevalence and characteristics of antibiotic allergy labels in a large UK hospital setting and estimate the proportion of penicillin allergy labels for which point-of-care (POC) delabeling assessment would be appropriate. METHODS: Electronic health records data were analyzed from all patients treated at Cambridge University Hospitals NHS Foundation Trust in 2019. Validated POC delabeling risk stratification criteria were retrospectively applied to penicillin allergy labels. RESULTS: Recorded reactions to antibiotics were present in 11.8% of all patients (32,148 of 273,216), 16.3% of inpatients (13,874 of 85,230), and 9.7% of outpatients (18,274 of 187,986). Penicillins were the commonest reaction precipitant described (9.0% of patients; 24,646 of 273,216), followed by sulfonamides/trimethoprim (1.4%; 3869 of 273,216) and macrolides/lincosamides (1.3%; 3644 of 273,216). A total of 3.9% of inpatients had recorded reactions to >1 antibiotic class (3348 of 85,230). Cutaneous manifestations were the most commonly described reaction features (40.7% of labels; 15,821 of 38,902). Of 15,949 labels describing probable or possible penicillin "allergy" with sufficient detail to allow for the retrospective assessment of POC delabeling suitability, 1702 were deemed suitable for removal or downgrading of the label to "intolerance" without further investigation (10.7%), 11,887 were appropriate for POC assessment using an oral penicillin challenge (OPC) or OPC with prior bedside skin testing (74.5%), and 2360 were identified as unsuitable for any form of POC assessment (14.8%). CONCLUSIONS: Antibiotic allergy labels are highly prevalent in a UK hospital setting. A large proportion of penicillin allergy labels may be suitable for POC delabeling assessment.

The seroincidence of childhood Shigella sonnei infection in Ho Chi Minh City, Vietnam.

BACKGROUND: Shigella sonnei is a pathogen of growing global importance as a cause of diarrhoeal illness in childhood, particularly in transitional low-middle income countries (LMICs). Here, we sought to determine the incidence of childhood exposure to S. sonnei infection in a contemporary transitional LMIC population, where it represents the dominant Shigella species. METHODS: Participants were enrolled between the age of 12-36 months between June and December 2014. Baseline characteristics were obtained through standardized electronic questionnaires, and serum samples were collected at 6-month intervals over two years of follow-up. IgG antibody against S. sonnei O-antigen (anti-O) was measured using an enzyme-linked immunosorbent assay (ELISA). A four-fold increase in ELISA units (EU) with convalescent IgG titre >10.3 EU was taken as evidence of seroconversion between timepoints. RESULTS: A total of 3,498 serum samples were collected from 748 participants; 3,170 from the 634 participants that completed follow-up. Measures of anti-O IgG varied significantly by calendar month (p = 0.03). Estimated S. sonnei seroincidence was 21,451 infections per 100,000 population per year (95% CI 19,307-23,834), with peak incidence occurring at 12-18 months of age. Three baseline factors were independently associated with the likelihood of seroconversion; ever having breastfed (aOR 2.54, CI 1.22-5.26), history of prior hospital admission (aOR 0.57, CI 0.34-0.95), and use of a toilet spray-wash in the household (aOR 0.42, CI 0.20-0.89). CONCLUSIONS: Incidence of S. sonnei exposure in Ho Chi Minh City is substantial, with significant reduction in the likelihood of exposure as age increases beyond 2 years.

A prospective study of risk factors associated with seroprevalence of SARS-CoV-2 antibodies in healthcare workers at a large UK teaching hospital.

OBJECTIVES: To describe the risk factors for SARS-CoV-2 infection in UK healthcare workers (HCWs). METHODS: We conducted a prospective sero-epidemiological study of HCWs at a major UK teaching hospital using a SARS-CoV-2 immunoassay. Risk factors for seropositivity were analysed using multivariate logistic regression. RESULTS: 410/5,698 (7·2%) staff tested positive for SARS-CoV-2 antibodies. Seroprevalence was higher in those working in designated COVID-19 areas compared with other areas (9·47% versus 6·16%) Healthcare assistants (aOR 2·06 [95%CI 1·14-3·71]; p=0·016) and domestic and portering staff (aOR 3·45 [95% CI 1·07-11·42]; p=0·039) had significantly higher seroprevalence than other staff groups after adjusting for age, sex, ethnicity and COVID-19 working location. Staff working in acute medicine and medical sub-specialities were also at higher risk (aOR 2·07 [95% CI 1·31-3·25]; p<0·002). Staff from Black, Asian and minority ethnic (BAME) backgrounds had an aOR of 1·65 (95% CI 1·32 - 2·07; p<0·001) compared to white staff; this increased risk was independent of COVID-19 area working. The only symptoms significantly associated with seropositivity in a multivariable model were loss of sense of taste or smell, fever, and myalgia; 31% of staff testing positive reported no prior symptoms. CONCLUSIONS: Risk of SARS-CoV-2 infection amongst HCWs is highly heterogeneous and influenced by COVID-19 working location, role, age and ethnicity. Increased risk amongst BAME staff cannot be accounted for solely by occupational factors.

Admission COVID-19 clinical risk assessment for guiding patient placement and diagnostic testing strategy.

INTRODUCTION: Without universal access to point-of-care SARS-CoV-2 testing, many hospitals rely on clinical judgement alone for identifying cases of COVID-19 early. METHODS: Cambridge University Hospitals NHS Foundation Trust introduced a 'traffic light' clinical judgement aid to the COVID-19 admissions unit in mid-March 2020. Ability to accurately predict COVID-19 was audited retrospectively across different stages of the epidemic. RESULTS: One SARS-CoV-2 PCR positive patient (1/41, 2%) was misallocated to a 'green' (non-COVID-19) area during the first period of observation, and no patients (0/32, 0%) were mislabelled 'green' during the second period. 33 of 62 (53%) labelled 'red' (high risk) tested SARS-CoV-2 PCR positive during the first period, while 5 of 22 (23%) 'red' patients were PCR positive in the second. CONCLUSION: COVID-19 clinical risk stratification on initial assessment effectively identifies non-COVID-19 patients. However, diagnosing COVID-19 is challenging and risk of overcalling COVID-19 should be recognised, especially when background prevalence is low.

Single-dose BNT162b2 vaccine protects against asymptomatic SARS-CoV-2 infection.

The BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech) is being utilised internationally for mass COVID-19 vaccination. Evidence of single-dose protection against symptomatic disease has encouraged some countries to opt for delayed booster doses of BNT162b2, but the effect of this strategy on rates of asymptomatic SARS-CoV-2 infection remains unknown. We previously demonstrated frequent pauci- and asymptomatic SARS-CoV-2 infection amongst healthcare workers (HCWs) during the UK's first wave of the COVID-19 pandemic, using a comprehensive PCR-based HCW screening programme (Rivett et al., 2020; Jones et al., 2020). Here, we evaluate the effect of first-dose BNT162b2 vaccination on test positivity rates and find a fourfold reduction in asymptomatic infection amongst HCWs ≥12 days post-vaccination. These data provide real-world evidence of short-term protection against asymptomatic SARS-CoV-2 infection following a single dose of BNT162b2 vaccine, suggesting that mass first-dose vaccination will reduce SARS-CoV-2 transmission, as well as the burden of COVID-19 disease.

Superspreaders drive the largest outbreaks of hospital onset COVID-19 infections.

SARS-CoV-2 is notable both for its rapid spread, and for the heterogeneity of its patterns of transmission, with multiple published incidences of superspreading behaviour. Here, we applied a novel network reconstruction algorithm to infer patterns of viral transmission occurring between patients and health care workers (HCWs) in the largest clusters of COVID-19 infection identified during the first wave of the epidemic at Cambridge University Hospitals NHS Foundation Trust, UK. Based upon dates of individuals reporting symptoms, recorded individual locations, and viral genome sequence data, we show an uneven pattern of transmission between individuals, with patients being much more likely to be infected by other patients than by HCWs. Further, the data were consistent with a pattern of superspreading, whereby 21% of individuals caused 80% of transmission events. Our study provides a detailed retrospective analysis of nosocomial SARS-CoV-2 transmission, and sheds light on the need for intensive and pervasive infection control procedures.

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, presents a global public health challenge. Hospitals have been at the forefront of this battle, treating large numbers of sick patients over several waves of infection. Finding ways to manage the spread of the virus in hospitals is key to protecting vulnerable patients and workers, while keeping hospitals running, but to generate effective infection control, researchers must understand how SARS-CoV-2 spreads. A range of factors make studying the transmission of SARS-CoV-2 in hospitals tricky. For instance, some people do not present any symptoms, and, amongst those who do, it can be difficult to determine whether they caught the virus in the hospital or somewhere else. However, comparing the genetic information of the SARS-CoV-2 virus from different people in a hospital could allow scientists to understand how it spreads. Samples of the genetic material of SARS-CoV-2 can be obtained by swabbing infected individuals. If the genetic sequences of two samples are very different, it is unlikely that the individuals who provided the samples transmitted the virus to one another. Illingworth, Hamilton et al. used this information, along with other data about how SARS-CoV-2 is transmitted, to develop an algorithm that can determine how the virus spreads from person to person in different hospital wards. To build their algorithm, Illingworth, Hamilton et al. collected SARS-CoV-2 genetic data from patients and staff in a hospital, and combined it with information about how SARS-CoV-2 spreads and how these people moved in the hospital . The algorithm showed that, for the most part, patients were infected by other patients (20 out of 22 cases), while staff were infected equally by patients and staff. By further probing these data, Illingworth, Hamilton et al. revealed that 80% of hospital-acquired infections were caused by a group of just 21% of individuals in the study, identifying a 'superspreader' pattern. These findings may help to inform SARS-CoV-2 infection control measures to reduce spread within hospitals, and could potentially be used to improve infection control in other contexts.

Evaluating the use of a 22-pathogen TaqMan array card for rapid diagnosis of respiratory pathogens in intensive care.

Introduction. Pneumonia is highly prevalent in intensive care units (ICUs), with high associated mortality. Empirical treatment prioritizes breadth of coverage while awaiting laboratory diagnosis, often at the expense of antimicrobial stewardship. Microarrays use multiple parallel polymerase chain reactions to enable a rapid syndromic approach to laboratory diagnosis.Aim. To evaluate the clinical and laboratory implications of introducing a bespoke 22-pathogen TaqMan Array Card (TAC) for rapid pathogen detection in deep respiratory samples from adult ICUs.Methodology. TAC results from all ICU patients prospectively tested over a 9-month period at Cambridge's Clinical Microbiology and Public Health Laboratory were compared to those of corresponding conventional microbiological assays (culture-, PCR- or serology-based) in terms of result agreement and time-to-result availability. Clinical impact was assessed by retrospective review of medical records.Results. Seventy-one patients were included [45 (63 %) male, median age 59). Overall result agreement was 94 %, with TAC detecting more pathogens than conventional methods. TAC detected Streptococcus pneumoniae more readily than culture (7 vs 0 cases; P=0.02). TAC did not detect Aspergillus spp. in eight culture- or galactomannan-positive cases. The median turnaround time (1 day) was significantly shorter than that of bacterial/fungal culture, Pneumocystis jirovecii PCR and galactomannan testing (each 3 days; P<0.001), atypical bacteria serology (13 days; P<0.001) and Mycobacterium tuberculosis culture (46 days; P<0.001). Earlier result availability prompted discontinuation of unnecessary antimicrobials in 15/71 (21 %) cases, but had no bearing on patient isolation/deisolation.Conclusion. TAC provided greater overall yield of pathogen detection and faster turnaround times, permitting earlier discontinuation of unnecessary antimicrobials.

Metformin as adjunctive therapy for dengue in overweight and obese patients: a protocol for an open-label clinical trial (MeDO).

Background:  Dengue is a disease of major global importance. While most symptomatic infections are mild, a small proportion of patients progress to severe disease with risk of hypovolaemic shock, organ dysfunction and death.  In the absence of effective antiviral or disease modifying drugs, clinical management is solely reliant on supportive measures. Obesity is a growing problem among young people in Vietnam and is increasingly recognised as an important risk factor for severe dengue, likely due to alterations in host immune and inflammatory pathways. Metformin, a widely used anti-hyperglycaemic agent with excellent safety profile, has demonstrated potential as a dengue therapeutic in vitro and in a retrospective observational study of adult dengue patients with type 2 diabetes.  This study aims to assess the safety and tolerability of metformin treatment in overweight and obese dengue patients, and investigate its effects on several clinical, immunological and virological markers of disease severity. Methods: This open label trial of 120 obese/overweight dengue patients will be performed in two phases, with a metformin dose escalation if no safety concerns arise in phase one. The primary endpoint is identification of clinical and laboratory adverse events.  Sixty overweight and obese dengue patients aged 10-30 years will be enrolled at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam. Participants will complete a 5-day course of metformin therapy and be compared to a non-treated group of 60 age-matched overweight and obese dengue patients. Discussion:  Previously observed antiviral and immunomodulatory effects of metformin make it a promising dengue therapeutic candidate in appropriately selected patients. This study will assess the safety and tolerability of adjunctive metformin in the management of overweight and obese young dengue patients, as well as its effects on markers of viral replication, endothelial dysfunction and host immune responses.  Trial registration: ClinicalTrials.gov: NCT04377451 (May 6 th 2020).

Screening of healthcare workers for SARS-CoV-2 highlights the role of asymptomatic carriage in COVID-19 transmission.

Significant differences exist in the availability of healthcare worker (HCW) SARS-CoV-2 testing between countries, and existing programmes focus on screening symptomatic rather than asymptomatic staff. Over a 3 week period (April 2020), 1032 asymptomatic HCWs were screened for SARS-CoV-2 in a large UK teaching hospital. Symptomatic staff and symptomatic household contacts were additionally tested. Real-time RT-PCR was used to detect viral RNA from a throat+nose self-swab. 3% of HCWs in the asymptomatic screening group tested positive for SARS-CoV-2. 17/30 (57%) were truly asymptomatic/pauci-symptomatic. 12/30 (40%) had experienced symptoms compatible with coronavirus disease 2019 (COVID-19)>7 days prior to testing, most self-isolating, returning well. Clusters of HCW infection were discovered on two independent wards. Viral genome sequencing showed that the majority of HCWs had the dominant lineage B∙1. Our data demonstrates the utility of comprehensive screening of HCWs with minimal or no symptoms. This approach will be critical for protecting patients and hospital staff.

Patients admitted to NHS hospitals are now routinely screened for SARS-CoV-2 (the virus that causes COVID-19), and isolated from other patients if necessary. Yet healthcare workers, including frontline patient-facing staff such as doctors, nurses and physiotherapists, are only tested and excluded from work if they develop symptoms of the illness. However, there is emerging evidence that many people infected with SARS-CoV-2 never develop significant symptoms: these people will therefore be missed by 'symptomatic-only' testing. There is also important data showing that around half of all transmissions of SARS-CoV-2 happen before the infected individual even develops symptoms. This means that much broader testing programs are required to spot people when they are most infectious. Rivett, Sridhar, Sparkes, Routledge et al. set out to determine what proportion of healthcare workers was infected with SARS-CoV-2 while also feeling generally healthy at the time of testing. Over 1,000 staff members at a large UK hospital who felt they were well enough to work, and did not fit the government criteria for COVID-19 infection, were tested. Amongst these, 3% were positive for SARS-CoV-2. On closer questioning, around one in five reported no symptoms, two in five very mild symptoms that they had dismissed as inconsequential, and a further two in five reported COVID-19 symptoms that had stopped more than a week previously. In parallel, healthcare workers with symptoms of COVID-19 (and their household contacts) who were self-isolating were also tested, in order to allow those without the virus to quickly return to work and bolster a stretched workforce. Finally, the rates of infection were examined to probe how the virus could have spread through the hospital and among staff ­ and in particular, to understand whether rates of infection were greater among staff working in areas devoted to COVID-19 patients. Despite wearing appropriate personal protective equipment, healthcare workers in these areas were almost three times more likely to test positive than those working in areas without COVID-19 patients. However, it is not clear whether this genuinely reflects greater rates of patients passing the infection to staff. Staff may give the virus to each other, or even acquire it at home. Overall, this work implies that hospitals need to be vigilant and introduce broad screening programmes across their workforces. It will be vital to establish such approaches before 'lockdown' is fully lifted, so healthcare institutions are prepared for any second peak of infections.

Effective control of SARS-CoV-2 transmission between healthcare workers during a period of diminished community prevalence of COVID-19.

Previously, we showed that 3% (31/1032)of asymptomatic healthcare workers (HCWs) from a large teaching hospital in Cambridge, UK, tested positive for SARS-CoV-2 in April 2020. About 15% (26/169) HCWs with symptoms of coronavirus disease 2019 (COVID-19) also tested positive for SARS-CoV-2 (Rivett et al., 2020). Here, we show that the proportion of both asymptomatic and symptomatic HCWs testing positive for SARS-CoV-2 rapidly declined to near-zero between 25th April and 24th May 2020, corresponding to a decline in patient admissions with COVID-19 during the ongoing UK 'lockdown'. These data demonstrate how infection prevention and control measures including staff testing may help prevent hospitals from becoming independent 'hubs' of SARS-CoV-2 transmission, and illustrate how, with appropriate precautions, organizations in other sectors may be able to resume on-site work safely.

Adenovirus pseudo-outbreak in a large UK neonatal intensive care unit.

An unusually high number of positive adenovirus stool antigen tests were observed in neonatal samples from a large tertiary referral unit over a 10-week period, prompting the declaration of an outbreak and escalation of infection control precautions. Subsequent testing of original samples by alternative methods revealed a series of false-positive results. This is the first adenovirus pseudo-outbreak to be reported in the United Kingdom and the first to involve the Proflow Rotavirus-Adenovirus Combi test.