Improving care for patients with Clostridioides difficile infection: A clinical practice and healthcare systems perspective.

Introduction: Arriving at a C. difficile infection (CDI) diagnosis, treating patients and dealing with recurrences is not straightforward, but a comprehensive and well-rounded understanding of what is needed to improve patient care is lacking. This manuscript addresses the paucity of multidisciplinary perspectives that consider clinical practice related and healthcare system-related challenges to optimizing care delivery. Methods: We draw on narrative review, consultations with clinical experts and patient representatives, and a survey of 95 clinical and microbiology experts from the UK, France, Italy, Australia and Canada, adding novel multi-method evidence to the knowledge base. Results and discussion: We examine the patient pathway and variations in clinical practice and identify, synthesize insights on and discuss associated challenges. Examples of key challenges include the need to conduct multiple tests for a conclusive diagnosis, treatment side-effects, the cost of some antibiotics and barriers to access of fecal microbiota transplantation, difficulties in distinguishing recurrence from new infection, workforce capacity constraints to effective monitoring of patients on treatment and of recurrence, and ascertaining whether a patient has been cured. We also identify key opportunities and priorities for improving patient care that target both clinical practice and the wider healthcare system. While there is some variety across surveyed countries' healthcare systems, there is also strong agreement on some priorities. Key improvement actions seen as priorities by at least half of survey respondents in at least three of the five surveyed countries include: developing innovative products for both preventing (Canada, Australia, UK, Italy, and France) and treating (Canada, Australia, and Italy) recurrences; facilitating more multidisciplinary patient care (UK, Australia, and France); updating diagnosis and treatment guidelines (Australia, Canada, and UK); and educating and supporting professionals in primary care (Italy, UK, Canada, and Australia) and those in secondary care who are not CDI experts (Italy, Australia, and France) on identifying symptoms and managing patients. Finally, we discuss key evidence gaps for a future research agenda.

Tracking COVID-19 via sewage.

PURPOSE OF REVIEW: We discuss the potential role of the faecal chain in COVID-19 and highlight recent studies using waste water-based epidemiology (WBE) to track severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RECENT FINDINGS: WBE has been suggested as an adjunct to improve disease surveillance and aid early detection of circulating disease. SARS-CoV-2, the aetiological agent of COVID-19, is an enveloped virus, and as such, typically not associated with the waste water environment, given high susceptibility to degradation in aqueous conditions. A review of the current literature supports the ability to detect of SARS-CoV-2 in waste water and suggests methods to predict community prevalence based on viral quantification. SUMMARY: The summary of current practices shows that while the isolation of SARS-CoV-2 is possible from waste water, issues remain regarding the efficacy of virial concentration and subsequent quantification and alignment with epidemiological data.

Multicenter Diagnostic Evaluation of a Novel Coronavirus Antigen Lateral Flow Test among Symptomatic Individuals in Brazil and the United Kingdom.

The COVID-19 pandemic has led to the commercialization of many antigen-based rapid diagnostic tests (Ag-RDTs), requiring independent evaluations. This report describes the clinical evaluation of the Novel Coronavirus 2019-nCoV Antigen Test (Colloidal Gold) (Beijing Hotgen Biotech Co., Ltd.), at two sites within Brazil and one in the United Kingdom. The collected samples (446 nasal swabs from Brazil and 246 nasopharyngeal samples from the UK) were analyzed by the Ag-RDT and compared to reverse transcription-quantitative PCR (RT-qPCR). Analytical evaluation of the Ag-RDT was performed using direct culture supernatants of SARS-CoV-2 strains from the wild-type (B.1), Alpha (B.1.1.7), Delta (B.1.617.2), Gamma (P.1), and Omicron (B.1.1.529) lineages. An overall sensitivity and specificity of 88.2% (95% confidence interval [CI], 81.3 to 93.3) and 100.0% (95% CI, 99.1 to 100.0), respectively, were obtained for the Brazilian and UK cohorts. The analytical limit of detection was determined as 1.0 × 103 PFU/mL (Alpha), 2.5 × 102 PFU/mL (Delta), 2.5 × 103 PFU/mL (Gamma), and 1.0 × 103 PFU/mL (Omicron), giving a viral copy equivalent of approximately 2.1 × 104 copies/mL, 9.0 × 105 copies/mL, 1.7 × 106 copies/mL, and 1.8 × 105 copies/mL for the Ag-RDT, respectively. Overall, while a higher sensitivity was claimed by the manufacturers than that found in this study, this evaluation finds that the Ag-RDT meets the WHO minimum performance requirements for sensitivity and specificity of COVID-19 Ag-RDTs. This study illustrates the comparative performance of the Hotgen Ag-RDT across two global settings and considers the different approaches in evaluation methods. IMPORTANCE Since the beginning of the SARS-CoV-2 pandemic, we have witnessed growing numbers of antigen rapid diagnostic tests (Ag-RDTs) being brought to market. In the United Kingdom, this was somewhat controlled indirectly as the government offered free tests from a small number of companies. However, as this has now ceased, individuals are responsible for their own acquisition of test kits. Similarly in Brazil, as of January 2022, pharmacies and other health care retailers are permitted to sell Ag-RDTs directly to the community. Many of these Ag-RDTs have not been externally evaluated, and results are not readily available to the public. Thus, there is now a need for a transparent evaluation of Ag-RDTs with both analytical and clinical evaluation. We present an independent review of the Novel Coronavirus 2019-nCoV Antigen Test (Colloidal Gold) (Beijing Hotgen Biotech Co., Ltd.), at two sites within Brazil and one in the United Kingdom.

A global perspective on improving patient care in uncomplicated urinary tract infection: expert consensus and practical guidance.

OBJECTIVES: Uncomplicated urinary tract infections (uUTIs) are a common problem in female patients. Management is mainly based on empirical prescribing, but there are concerns about overtreatment and antimicrobial resistance (AMR), especially in patients with recurrent uUTIs. METHODS: A multidisciplinary panel of experts met to discuss diagnosis, treatment, prevention, guidelines, AMR, clinical trial design and the impact of COVID-19 on clinical practice. RESULTS: Symptoms remain the cornerstone of uUTI diagnosis, and urine culture is necessary only when empirical treatment fails or rapid recurrence of symptoms or AMR is suspected. Specific antimicrobials are first-line therapy (typically nitrofurantoin, fosfomycin, trimethoprim/sulfamethoxazole and pivmecillinam, dependent on availability and local resistance data). Fluoroquinolones are not first-line options for uUTIs primarily due to safety concerns but also rising resistance rates. High-quality data to support most non-antimicrobial approaches are lacking. Local AMR data specific to community-acquired uUTIs are needed, but representative information is difficult to obtain; instead, identification of risk factors for AMR can provide a basis to guide empirical antimicrobial prescribing. The COVID-19 pandemic has impacted the management of uUTIs in some countries and may have long-lasting implications for future models of care. CONCLUSION: Management of uUTIs in female patients can be improved without increasing complexity, including simplified diagnosis and empirical antimicrobial prescribing based on patient characteristics, including a review of recent antimicrobial use and past pathogen resistance profiles, drug availability and guidelines. Current data for non-antimicrobial approaches are limited. The influence of COVID-19 on telehealth could provide an opportunity to enhance patient care in the long term.

Modeling fomite-mediated SARS-CoV-2 exposure through personal protective equipment doffing in a hospital environment.

Self-contamination during doffing of personal protective equipment (PPE) is a concern for healthcare workers (HCW) following SARS-CoV-2-positive patient care. Staff may subconsciously become contaminated through improper glove removal; so, quantifying this exposure is critical for safe working procedures. HCW surface contact sequences on a respiratory ward were modeled using a discrete-time Markov chain for: IV-drip care, blood pressure monitoring, and doctors' rounds. Accretion of viral RNA on gloves during care was modeled using a stochastic recurrence relation. In the simulation, the HCW then doffed PPE and contaminated themselves in a fraction of cases based on increasing caseload. A parametric study was conducted to analyze the effect of: (1a) increasing patient numbers on the ward, (1b) the proportion of COVID-19 cases, (2) the length of a shift, and (3) the probability of touching contaminated PPE. The driving factors for the exposure were surface contamination and the number of surface contacts. The results simulate generally low viral exposures in most of the scenarios considered including on 100% COVID-19 positive wards, although this is where the highest self-inoculated dose is likely to occur with median 0.0305 viruses (95% CI =0-0.6 viruses). Dose correlates highly with surface contamination showing that this can be a determining factor for the exposure. The infection risk resulting from the exposure is challenging to estimate, as it will be influenced by the factors such as virus variant and vaccination rates.

Can SARS-CoV-2 be transmitted via faeces?

PURPOSE OF REVIEW: COVID-19 patients can present gastrointestinal symptoms, being diarrhoea one of the most frequent, suggesting intestinal health can be impacted by COVID-19. Here, we will discuss whether there is a correlation between the presence of SARS-CoV-2 RNA in faeces and diarrhoea, the relevance of gastrointestinal symptoms in disease diagnosis and transmission, and how COVID-19 can impact the gut microbial balance. RECENT FINDINGS: SARS-CoV-2 RNA has been reported in faeces or rectal swabs of COVID-19 patients with and without diarrhoea, suggesting faecal shedding can occur independently of gastrointestinal symptoms. However, the presence of the virus in the intestine can persist beyond its presence in the respiratory tract, with some reports suggesting that SARS-CoV-2 in the faeces can be infectious.COVID-19 can impact the gut microbiota causing an enhancement of biosynthesis pathways that favour the expansion of bacterial pathogens in the inflamed gut, and causing a decline in commensals involved in the human immune response. SUMMARY: Gastrointestinal symptoms may be the first indication of COVID-19. SARS-CoV-2 in faeces can potentiate routes of disease transmission, particularly as the high viral loads reported in patients with severe illness suggest virus replication in the intestine may be possible.

Healthcare-associated COVID-19 in England: A national data linkage study.

OBJECTIVES: Nosocomial transmission was an important aspect of SARS-CoV-1 and MERS-CoV outbreaks. Healthcare-associated SARS-CoV-2 infection has been reported in single and multi-site hospital-based studies in England, but not nationally. METHODS: Admission records for all hospitals in England were linked to SARS-CoV-2 national test data for the period 01/03/2020 to 31/08/2020. Case definitions were: community-onset community-acquired, first positive test <14 days pre-admission, up to day 2 of admission; hospital-onset indeterminate healthcare-associated, first positive on day 3-7; hospital-onset probable healthcare-associated, first positive on day 8-14; hospital-onset definite healthcare-associated, first positive from day 15 of admission until discharge; community-onset possible healthcare-associated, first positive test ≤14 days post-discharge. RESULTS: One-third (34.4%, 100,859/293,204) of all laboratory-confirmed COVID-19 cases were linked to a hospital record. Hospital-onset probable and definite cases represented 5.3% (15,564/293,204) of all laboratory-confirmed cases and 15.4% (15,564/100,859) of laboratory-confirmed cases among hospital patients. Community-onset community-acquired and community-onset possible healthcare-associated cases represented 86.5% (253,582/293,204) and 5.1% (14,913/293,204) of all laboratory-confirmed cases, respectively. CONCLUSIONS: Up to 1 in 6 SARS-CoV-2 infections among hospitalised patients with COVID-19 in England during the first 6 months of the pandemic could be attributed to nosocomial transmission, but these represent less than 1% of the estimated 3 million COVID-19 cases in this period.

Performance of the Innova SARS-CoV-2 antigen rapid lateral flow test in the Liverpool asymptomatic testing pilot: population based cohort study.

OBJECTIVE: To assess the performance of the SARS-CoV-2 antigen rapid lateral flow test (LFT) versus polymerase chain reaction testing in the asymptomatic general population attending testing centres. DESIGN: Observational cohort study. SETTING: Community LFT pilot at covid-19 testing sites in Liverpool, UK. PARTICIPANTS: 5869 asymptomatic adults (≥18 years) voluntarily attending one of 48 testing sites during 6-29 November 2020. INTERVENTIONS: Participants were tested using both an Innova LFT and a quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR) test based on supervised self-administered swabbing at testing sites. MAIN OUTCOME MEASURES: Sensitivity, specificity, and predictive values of LFT compared with RT-qPCR in an epidemic steady state of covid-19 among adults with no classic symptoms of the disease. RESULTS: Of 5869 test results, 22 (0.4%) LFT results and 343 (5.8%) RT-qPCR results were void (that is, when the control line fails to appear within 30 minutes). Excluding the void results, the LFT versus RT-qPCR showed a sensitivity of 40.0% (95% confidence interval 28.5% to 52.4%; 28/70), specificity of 99.9% (99.8% to 99.99%; 5431/5434), positive predictive value of 90.3% (74.2% to 98.0%; 28/31), and negative predictive value of 99.2% (99.0% to 99.4%; 5431/5473). When the void samples were assumed to be negative, a sensitivity was observed for LFT of 37.8% (26.8% to 49.9%; 28/74), specificity of 99.6% (99.4% to 99.8%; 5431/5452), positive predictive value of 84.8% (68.1% to 94.9%; 28/33), and negative predictive value of 93.4% (92.7% to 94.0%; 5431/5814). The sensitivity in participants with an RT-qPCR cycle threshold (Ct) of <18.3 (approximate viral loads >106 RNA copies/mL) was 90.9% (58.7% to 99.8%; 10/11), a Ct of <24.4 (>104 RNA copies/mL) was 69.4% (51.9% to 83.7%; 25/36), and a Ct of >24.4 (<104 RNA copies/mL) was 9.7% (1.9% to 23.7%; 3/34). LFT is likely to detect at least three fifths and at most 998 in every 1000 people with a positive RT-qPCR test result with high viral load. CONCLUSIONS: The Innova LFT can be useful for identifying infections among adults who report no symptoms of covid-19, particularly those with high viral load who are more likely to infect others. The number of asymptomatic adults with lower Ct (indicating higher viral load) missed by LFT, although small, should be considered when using single LFT in high consequence settings. Clear and accurate communication with the public about how to interpret test results is important, given the chance of missing some cases, even at high viral loads. Further research is needed to understand how infectiousness is reflected in the viral antigen shedding detected by LFT versus the viral loads approximated by RT-qPCR.

The Efficacy and Safety of Fecal Microbiota Transplant for Recurrent Clostridium difficile Infection: Current Understanding and Gap Analysis.

The leading risk factor for Clostridioides (Clostridium) difficile infection (CDI) is broad-spectrum antibiotics, which lead to low microbial diversity, or dysbiosis. Current therapeutic strategies for CDI are insufficient, as they do not address the key role of the microbiome in preventing C. difficile spore germination into toxin-producing vegetative bacteria, which leads to symptomatic disease. Fecal microbiota transplant (FMT) appears to reduce the risk of recurrent CDI through microbiome restoration. However, a wide range of efficacy rates have been reported, and few placebo-controlled trials have been conducted, limiting our understanding of FMT efficacy and safety. We discuss the current knowledge gaps driven by questions around the quality and consistency of clinical trial results, patient selection, diagnostic methodologies, use of suppressive antibiotic therapy, and methods for adverse event reporting. We provide specific recommendations for future trial designs of FMT to provide improved quality of the clinical evidence to better inform treatment guidelines.

Shedding of SARS-CoV-2 in feces and urine and its potential role in person-to-person transmission and the environment-based spread of COVID-19.

The recent detection of SARS-CoV-2 RNA in feces has led to speculation that it can be transmitted via the fecal-oral/ocular route. This review aims to critically evaluate the incidence of gastrointestinal (GI) symptoms, the quantity and infectivity of SARS-CoV-2 in feces and urine, and whether these pose an infection risk in sanitary settings, sewage networks, wastewater treatment plants, and the wider environment (e.g. rivers, lakes and marine waters). A review of 48 independent studies revealed that severe GI dysfunction is only evident in a small number of COVID-19 cases, with 11 ± 2% exhibiting diarrhea and 12 ± 3% exhibiting vomiting and nausea. In addition to these cases, SARS-CoV-2 RNA can be detected in feces from some asymptomatic, mildly- and pre-symptomatic individuals. Fecal shedding of the virus peaks in the symptomatic period and can persist for several weeks, but with declining abundances in the post-symptomatic phase. SARS-CoV-2 RNA is occasionally detected in urine, but reports in fecal samples are more frequent. The abundance of the virus genetic material in both urine (ca. 102-105 gc/ml) and feces (ca. 102-107 gc/ml) is much lower than in nasopharyngeal fluids (ca. 105-1011 gc/ml). There is strong evidence of multiplication of SARS-CoV-2 in the gut and infectious virus has occasionally been recovered from both urine and stool samples. The level and infectious capability of SARS-CoV-2 in vomit remain unknown. In comparison to enteric viruses transmitted via the fecal-oral route (e.g. norovirus, adenovirus), the likelihood of SARS-CoV-2 being transmitted via feces or urine appears much lower due to the lower relative amounts of virus present in feces/urine. The biggest risk of transmission will occur in clinical and care home settings where secondary handling of people and urine/fecal matter occurs. In addition, while SARS-CoV-2 RNA genetic material can be detected by in wastewater, this signal is greatly reduced by conventional treatment. Our analysis also suggests the likelihood of infection due to contact with sewage-contaminated water (e.g. swimming, surfing, angling) or food (e.g. salads, shellfish) is extremely low or negligible based on very low predicted abundances and limited environmental survival of SARS-CoV-2. These conclusions are corroborated by the fact that tens of million cases of COVID-19 have occurred globally, but exposure to feces or wastewater has never been implicated as a transmission vector.

Snapshot PCR surveillance for SARS-CoV-2 in hospital staff in England.

BACKGROUND: Significant nosocomial transmission of SARS-CoV-2 has been demonstrated. Understanding the prevalence of SARS-CoV-2 carriage amongst HCWs at work is necessary to inform the development of HCW screening programmes to control nosocomial spread. METHODS: Cross-sectional 'snapshot' survey from April-May 2020; HCWs recruited from six UK hospitals. Participants self-completed a health questionnaire and underwent a combined viral nose and throat swab, tested by Polymerase Chain Reaction (PCR) for SARS-CoV-2 with viral culture on majority of positive samples. FINDINGS: Point prevalence of SARS-CoV-2 carriage across the sites was 2.0% (23/1152 participants), median cycle threshold value 35.70 (IQR:32.42-37.57). 17 were previously symptomatic, two currently symptomatic (isolated anosmia and sore throat); the remainder declared no prior or current symptoms. Symptoms in the past month were associated with threefold increased odds of testing positive (aOR 3.46, 95%CI 1.38-8.67; p = 0.008). SARS-CoV-2 virus was isolated from only one (5%) of nineteen cultured samples. A large proportion (39%) of participants reported symptoms in the past month. INTERPRETATION: The point-prevalence is similar to previous estimates for HCWs in April 2020, though a magnitude higher than in the general population. Based upon interpretation of symptom history and testing results including viral culture, the majority of those testing positive were unlikely to be infectious at time of sampling. Development of screening programmes must balance the potential to identify additional cases based upon likely prevalence, expanding the symptoms list to encourage HCW testing, with resource implications and risks of excluding those unlikely to be infectious with positive tests. FUNDING: Public Health England.