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Journal articleBoonyasiri A, Jauneikaite E, Brinkac LM, et al., 2021,
Genomic and clinical characterisation of multidrug-resistant carbapenemase-producing ST231 and ST16 Klebsiella pneumoniae isolates colonising patients at Siriraj hospital, Bangkok, Thailand from 2015 to 2017.
, BMC Infectious Diseases, Vol: 21, Pages: 1-11, ISSN: 1471-2334BACKGROUND: Infections caused by carbapenemase-producing Enterobacteriaceae (CPE) have continually grown as a global public health threat, with significant mortality rates observed across the world. We examined the clinical data from patients with CPE infections and their outcomes, concentrating on Klebsiella pneumoniae isolates. We analysed the clinical information, performed antimicrobial susceptibility testing, and conducted molecular epidemiological and genomic analyses on the isolates to identify patterns in the data. METHODS: The clinical characteristics of 33 hospitalised patients with confirmed CPE, including patient-related factors associated with the development of CPE infections, were examined. Patients were divided according to whether they were "colonised" or "infected" with CPE and by the timing and frequency of their rectal swab collections, from which 45 swabs were randomly selected for analysis. CPE isolates were purified, and antimicrobial susceptibility tests performed. Whole genome sequences of these isolates were determined and analysed to compute bacterial multilocus sequence types and plasmid replicon types, infer phylogenetic relationships, and identify antimicrobial resistance and virulence genes. RESULTS: Altogether, 88.9% (40/45) of the CPE isolates were K. pneumoniae. The most abundant carbapenemase gene family in the K. pneumoniae isolates (33/39) was blaOXA-232, with blaNDM-1 additionally identified in 19 of them. All CPE isolates carrying either blaOXA-232 or blaNDM-1 were resistant to meropenem, but only 40 from 45 were susceptible to colistin. Among the CPE-infected patients (n = 18) and CPE-colonised patients who developed CPE infections during the study (n = 3), all but one received standard colistin-based combination therapy. Phylogenetic analysis revealed the polyclonal spread of carbapenemase-producing K. pneumoniae (CPKP) within the patient population, with the following two major
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Journal articleBorek AJ, Campbell A, Dent E, et al., 2021,
Implementing interventions to reduce antibiotic use: a qualitative study in high-prescribing practices
, BMC Family Practice, Vol: 22, ISSN: 1471-2296BackgroundTrials have shown that delayed antibiotic prescriptions (DPs) and point-of-care C-Reactive Protein testing (POC-CRPT) are effective in reducing antibiotic use in general practice, but these were not typically implemented in high-prescribing practices. We aimed to explore views of professionals from high-prescribing practices about uptake and implementation of DPs and POC-CRPT to reduce antibiotic use.MethodsThis was a qualitative focus group study in English general practices. The highest antibiotic prescribing practices in the West Midlands were invited to participate. Clinical and non-clinical professionals attended focus groups co-facilitated by two researchers. Focus groups were audio-recorded, transcribed verbatim and analysed thematically.ResultsNine practices (50 professionals) participated. Four main themes were identified. Compatibility of strategies with clinical roles and experience – participants viewed the strategies as having limited value as ‘clinical tools’, perceiving them as useful only in ‘rare’ instances of clinical uncertainty and/or for those less experienced. Strategies as ‘social tools’ – participants perceived the strategies as helpful for negotiating treatment decisions and educating patients, particularly those expecting antibiotics. Ambiguities – participants perceived ambiguities around when they should be used, and about their impact on antibiotic use. Influence of context – various other situational and practical issues were raised with implementing the strategies.ConclusionsHigh-prescribing practices do not view DPs and POC-CRPT as sufficiently useful ‘clinical tools’ in a way which corresponds to the current policy approach advocating their use to reduce clinical uncertainty and improve antimicrobial stewardship. Instead, policy attention should focus on how these strategies may instead be used as ‘social tools’ to reduce unnecessary antibio
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Journal articlePrice JR, Mookerjee S, Dyakova E, et al., 2021,
Development and delivery of a real-time hospital-onset COVID-19 surveillance system using network analysis
, Clinical Infectious Diseases, Vol: 72, Pages: 82-89, ISSN: 1058-4838BackgroundUnderstanding nosocomial acquisition, outbreaks and transmission chains in real-time will be fundamental to ensuring infection prevention measures are effective in controlling COVID-19 in healthcare. We report the design and implementation of a hospital-onset COVID-19 infection (HOCI) surveillance system for an acute healthcare setting to target prevention interventions.MethodsThe study took place in a large teaching hospital group in London, UK. All patients tested for SARS-CoV-2 between 4th March and 14th April 2020 were included. Utilising data routinely collected through electronic healthcare systems we developed a novel surveillance system for determining and reporting HOCI incidence and providing real-time network analysis. We provided daily reports on incidence and trends over time to support HOCI investigation, and generated geo-temporal reports using network analysis to interrogate admission pathways for common epidemiological links to infer transmission chains. By working with stakeholders the reports were co-designed for end users.ResultsReal-time surveillance reports revealed: changing rates of HOCI throughout the course of the COVID-19 epidemic; key wards fuelling probable transmission events; HOCIs over-represented in particular specialities managing high-risk patients; the importance of integrating analysis of individual prior pathways; and the value of co-design in producing data visualisation. Our surveillance system can effectively support national surveillance.ConclusionsThrough early analysis of the novel surveillance system we have provided a description of HOCI rates and trends over time using real-time shifting denominator data. We demonstrate the importance of including the analysis of patient pathways and networks in characterising risk of transmission and targeting infection control interventions.
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Journal articleZhu NJ, McLeod M, McNulty CAM, et al., 2021,
Trends in Antibiotic Prescribing in Out-of-Hours Primary Care in England from January 2016 to June 2020 to Understand Behaviours during the First Wave of COVID-19
, ANTIBIOTICS-BASEL, Vol: 10, ISSN: 2079-6382- Author Web Link
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Journal articleCastro-Sanchez E, Alexander CM, Atchison C, et al., 2020,
Evaluation of a personal protective equipment (PPE) support programme ('PPE Helpers') for staff during the COVID-19 pandemic in London
, Journal of Hospital Infection, Vol: 109, Pages: 68-7, ISSN: 0195-6701BackgroundThe COVID-19 pandemic has presented one of the biggest challenges to healthcare providers worldwide. The appropriate use of Personal Protective Equipment (PPE) has been essential to ensuring staff and patient safety. To counteract sub-optimal PPE practice, a PPE helper programme was developed at a large London hospital group. Based on a behaviour change model of Capability, Opportunity and Motivation (COM-B), the programme provided PPE support, advice and education to ward staff.AimEvaluation of the PPE Helper Programme.MethodsClinical and non-clinical ward staff completed a questionnaire informed by the Theoretical Domains Framework and COM-B. The questionnaire was available in paper and electronic versions. Quantitative responses were analysed using descriptive and non-parametric statistics, free-text responses were analysed thematically.FindingsOver a six-week period, PPE helpers made 268 ward visits. Overall, 261 questionnaires were available for analysis. Across the Trust, 68% of respondents reported having had contact with a PPE helper. Staff who had encountered a PPE helper responded significantly more positively to a range of statements about using PPE than those who had not. Black and Minority Ethnic (BAME) staff were significantly more anxious in relation to the adequacy of PPE. Non-clinical and redeployed staff (e.g. domestic staff) were most positive about the impact of PPE helpers. Free-text comments showed that staff found the programme supportive and would have liked it earlier in the pandemic.ConclusionA PPE Helper programme is a feasible and beneficial intervention for providing support, advice and education to ward staff during infectious disease outbreaks.
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Journal articleNaylor N, Yamashita K, Iwami M, et al., 2020,
Code-sharing in cost-of-illness calculations: an application to antibiotic-resistant bloodstream infections
, Frontiers in Public Health, Vol: 8, ISSN: 2296-2565Background: More data-driven evidence is needed on the cost of antibiotic resistance. Both Japan and England have large surveillance and administrative datasets. Code sharing of costing models enables reduced duplication of effort in research.Objective: To estimate the burden of antibiotic-resistant Staphylococcus aureus bloodstream infections (BSIs) in Japan, utilizing code that was written to estimate the hospital burden of antibiotic-resistant Escherichia coli BSIs in England. Additionally, the process in which the code-sharing and application was performed is detailed, to aid future such use of code-sharing in health economics.Methods: National administrative data sources were linked with voluntary surveillance data within the Japan case study. R software code, which created multistate models to estimate the excess length of stay associated with different exposures of interest, was adapted from previous use and run on this dataset. Unit costs were applied to estimate healthcare system burden in 2017 international dollars (I$).Results: Clear supporting documentation alongside open-access code, licensing, and formal communication channels, helped the re-application of costing code from the English setting within the Japanese setting. From the Japanese healthcare system perspective, it was estimated that there was an excess cost of I$6,392 per S. aureus BSI, whilst oxacillin resistance was associated with an additional I$8,155.Conclusions: S. aureus resistance profiles other than methicillin may substantially impact hospital costs. The sharing of costing models within the field of antibiotic resistance is a feasible way to increase burden evidence efficiently, allowing for decision makers (with appropriate data available) to gain rapid cost-of-illness estimates.
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Journal articleEllington MJ, Davies F, Jauneikaite E, et al., 2020,
A multi-species cluster of GES-5 carbapenemase producing Enterobacterales linked by a geographically disseminated plasmid
, Clinical Infectious Diseases, Vol: 71, Pages: 2553-2560, ISSN: 1058-4838BACKGROUND: Early and accurate treatment of infections due to carbapenem-resistant organisms is facilitated by rapid diagnostics but rare resistance mechanisms can compromise detection. One year after a GES-5 carbapenemase-positive Klebsiella oxytoca infection was identified by whole genome sequencing (WGS) (later found to be part of a cluster of three cases), a cluster of 11 patients with GES-5-positive K. oxytoca was identified over 18 weeks in the same hospital.METHODS: Bacteria were identified by MALDI-TOF, antimicrobial susceptibility testing followed EUCAST guidelines. Ertapenem-resistant isolates were referred to Public Health England for characterization using PCR detection of GES, pulse-field gel electrophoresis (PFGE) and WGS for the second cluster.RESULTS: The identification of the first GES-5 K. oxytoca isolate was delayed, being identified on WGS. A GES-gene PCR informed the occurrence of the second cluster in real-time. In contrast to PFGE, WGS phylogenetic analysis refuted an epidemiological link between the two clusters; it also suggested a cascade of patient-to-patient transmission in the later cluster. A novel GES-5-encoding plasmid was present in K. oxytoca,E. coli and E. cloacae isolates from unlinked patients within the same hospital group and in human and wastewater isolates from three hospitals elsewhere in the UK.CONCLUSIONS: Genomic sequencing revolutionized the epidemiological understanding of the clusters, it also underlined the risk of covert plasmid propagation in healthcare settings and revealed the national distribution of the resistance-encoding plasmid. Sequencing results also informed and led to the ongoing use of enhanced diagnostic tests for detecting carbapenemases locally and nationally.
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Journal articleCharani E, Singh S, Mendelson M, et al., 2020,
Building resilient and responsive research collaborations to tackle antimicrobial resistance – lessons learnt from India, South Africa and UK
, International Journal of Infectious Diseases, Vol: 100, Pages: 278-282, ISSN: 1201-9712Research, collaboration and knowledge exchange are critical to global efforts to tackle antimicrobial resistance (AMR). Different healthcare economies are faced with different challenges in implementing effective strategies to address AMR. Building effective capacity for research to inform AMR related strategies and policies AMR is recognised as an important contributor to success. Interdisciplinary, inter-sector, as well as inter-country collaboration is needed to span AMR efforts from the global to local. Developing reciprocal, long-term, partnerships between collaborators in high-income and low- and middle-income countries (LMICs) needs to be built on principles of capacity building. Using case-studies spanning local to international research collaborations to co-design, implement and evaluate strategies to tackle AMR, we evaluate and build upon the ESSENCE criteria for capacity building in LMICs. The first case-study describes the local co-design and implementation of antimicrobial stewardship in the state of Kerala in India. The second case-study describes an international research collaboration investigating AMR across surgical pathways in India, UK and South Africa. We describe the steps undertaken to develop robust, agile, and flexible antimicrobial stewardship research and implementation teams. Notably, investing in capacity building ensured that the programmes described in these case-studies were sustained through the current severe acute respiratory syndrome corona virus pandemic. Describing the strategies adopted by a local and an international collaboration to tackle AMR, we provide a model for capacity building in LMICs that can support sustainable and agile antimicrobial stewardship programmes.
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Journal articleHughes S, Troise O, Donaldson H, et al., 2020,
Bacterial and fungal coinfection among hospitalised patients with COVID-19: A retrospective cohort study in a UK secondary care setting
, Clinical Microbiology and Infection, Vol: 26, Pages: 1395-1399, ISSN: 1198-743XObjectivesWe investigate the incidence of bacterial and fungal co-infection of hospitalised patients with confirmed SARS-CoV-2 in this retrospective observational study across two London hospitals during the first UK wave of COVID-19.MethodsA retrospective case-series of hospitalised patients with confirmed SARS-CoV-2 by PCR was analysed across two acute NHS hospitals (February 20–April 20; each isolate reviewed independently in parallel). This was contrasted to a control group of influenza positive patients admitted during 2019/20 flu season. Patient demographics, microbiology, and clinical outcomes were analysed.Results836 patients with confirmed SARS-CoV-2 were included; 27/836(3.2%) had early confirmed bacterial isolates identified (0-5 days post-admission) rising to 51/836(6.1%) throughout admission. Blood cultures, respiratory samples, pneumococcal or legionella urinary antigens, and respiratory viral PCR panels were obtained from 643(77%), 112(13%), 249(30%), 246(29%) and 250(30%) COVID-19 patients, respectively. A positive blood culture was identified in 60(7.1%) patients, of which 39/60 were classified as contaminants. Bacteraemia secondary to respiratory infection was confirmed in two cases (1 community-acquired K. pneumoniae and 1 ventilator-associated E. cloacae). Line-related bacteraemia was identified in six patients (3 candida, 2 Enterococcus spp. and 1 Pseudomonas aeruginosa). All other community acquired bacteraemias(16) were attributed to non-respiratory infection. Zero concomitant pneumococcal, legionella or influenza infection was detected. A low yield of positive respiratory cultures was identified; S. aureus the most common respiratory pathogen isolated in community-acquired coinfection (4/24;16.7%) with pseudomonas and yeast identified in late-onset infection. Invasive fungal infections (n=3) were attributed to line related infections. Comparable rates of positive co-infection were identified in the control group of confirmed influenza i
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Journal articleMoniri A, Miglietta L, Holmes A, et al., 2020,
High-level multiplexing in digital PCR with intercalating dyes by coupling real-time kinetics and melting curve analysis.
, Analytical Chemistry, Vol: 92, Pages: 14181-14188, ISSN: 0003-2700Digital polymerase chain reaction (dPCR) is a mature technique that has enabled scientific breakthroughs in several fields. However, this technology is primarily used in research environments with high-level multiplexing representing a major challenge. Here, we propose a novel method for multiplexing, referred to as amplification and melting curve analysis (AMCA), which leverages the kinetic information in real-time amplification data and the thermodynamic melting profile using an affordable intercalating dye (EvaGreen). The method trains a system comprised of supervised machine learning models for accurate classification, by virtue of the large volume of data from dPCR platforms. As a case study, we develop a new 9-plex assay to detect mobilised colistin resistant (mcr) genes as clinically relevant targets for antimicrobial resistance. Over 100,000 amplification events have been analysed, and for the positive reactions, the AMCA approach reports a classification accuracy of 99.33 ± 0.13%, an increase of 10.0% over using melting curve analysis. This work provides an affordable method of high-level multiplexing without fluorescent probes, extending the benefits of dPCR in research and clinical settings.
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