Imperial College London

ProfessorAlisonHolmes

Faculty of MedicineDepartment of Infectious Disease

Professor of Infectious Diseases
 
 
 
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Contact

 

+44 (0)20 3313 1283alison.holmes

 
 
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Location

 

8N16Hammersmith HospitalHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

332 results found

McLeod J, Stadler E, Wilson R, Holmes A, O'Hare Det al., 2021, Electrochemical detection of cefiderocol for therapeutic drug monitoring, ELECTROCHEMISTRY COMMUNICATIONS, Vol: 133, ISSN: 1388-2481

Journal article

Charani E, Mendelson M, Ashiru-Oredope D, Hutchinson E, Kaur M, McKee M, Mpundu M, Price JR, Shafiq N, Holmes Aet al., 2021, Navigating sociocultural disparities in relation to infection and antibiotic resistance-the need for an intersectional approach., JAC Antimicrob Resist, Vol: 3

One of the key drivers of antibiotic resistance (ABR) and drug-resistant bacterial infections is the misuse and overuse of antibiotics in human populations. Infection management and antibiotic decision-making are multifactorial, complex processes influenced by context and involving many actors. Social constructs including race, ethnicity, gender identity and cultural and religious practices as well as migration status and geography influence health. Infection and ABR are also affected by these external drivers in individuals and populations leading to stratified health outcomes. These drivers compromise the capacity and resources of healthcare services already over-burdened with drug-resistant infections. In this review we consider the current evidence and call for a need to broaden the study of culture and power dynamics in healthcare through investigation of relative power, hierarchies and sociocultural constructs including structures, race, caste, social class and gender identity as predictors of health-providing and health-seeking behaviours. This approach will facilitate a more sustainable means of addressing the threat of ABR and identify vulnerable groups ensuring greater inclusivity in decision-making. At an individual level, investigating how social constructs and gender hierarchies impact clinical team interactions, communication and decision-making in infection management and the role of the patient and carers will support better engagement to optimize behaviours. How people of different race, class and gender identity seek, experience and provide healthcare for bacterial infections and use antibiotics needs to be better understood in order to facilitate inclusivity of marginalized groups in decision-making and policy.

Journal article

Rawson TM, Wilson R, Moore L, Macgowan A, Lovering A, Bayliss M, Kyriakides M, Gilchrist M, Roberts J, Hope W, Holmes Aet al., 2021, Exploring the pharmacokinetics of phenoxymethylpenicillin (Penicillin-V) in adults: a healthy volunteer study, Open Forum Infectious Diseases, ISSN: 2328-8957

Journal article

Boonyasiri A, Myall AC, Wan Y, Bolt F, Ledda A, Mookerjee S, Weiße AY, Turton JF, Abbas H, Prakapaite R, Sabnis A, Abdolrasouli A, Malpartida-Cardenas K, Miglietta L, Donaldson H, Gilchrist M, Hopkins KL, Ellington MJ, Otter JA, Larrouy-Maumus G, Edwards AM, Rodriguez-Manzano J, Didelot X, Barahona M, Holmes AH, Jauneikaite E, Davies Fet al., 2021, Integrated patient network and genomic plasmid analysis reveal a regional, multi-species outbreak of carbapenemase-producing Enterobacterales carrying both blaIMP and mcr-9 genes

<jats:title>Abstract</jats:title><jats:p>The incidence of carbapenemase-producing Enterobacterales (CPE) is rising globally, yet Imipenemase (IMP) carbapenemases remain relatively rare. This study describes an investigation of the emergence of IMP-encoding CPE amongst diverse Enterobacterales species between 2016 and 2019 in patients across a London regional hospital network.</jats:p><jats:p>A network analysis approach to patient pathways, using routinely collected electronic health records, identified previously unrecognised contacts between patients who were IMP CPE positive on screening, implying potential bacterial transmission events. Whole genome sequencing of 85 Enterobacterales isolates from these patients revealed that 86% (73/85) were diverse species (predominantly <jats:italic>Klebsiella</jats:italic> spp, <jats:italic>Enterobacter</jats:italic> spp, <jats:italic>E. coli</jats:italic>) and harboured an IncHI2 plasmid, which carried both <jats:italic>bla</jats:italic><jats:sub>IMP</jats:sub> and the putative mobile colistin resistance gene <jats:italic>mcr-9</jats:italic>. Detailed phylogenetic analysis identified two distinct IncHI2 plasmid lineages, A and B, both of which showed significant association with patient movements between four hospital sites and across medical specialities.</jats:p><jats:p>Combined, our patient network and plasmid analyses demonstrate an interspecies, plasmid-mediated outbreak of <jats:italic>bla</jats:italic><jats:sub>IMP</jats:sub>CPE, which remained unidentified during standard microbiology and infection control investigations. With whole genome sequencing (WGS) technologies and large-data incorporation, the outbreak investigation approach proposed here provides a framework for real-time identification of key factors causing pathogen spread. Analysing outbreaks at the plasmid level reveal

Journal article

Shafiq N, Pandey AK, Malhotra S, Holmes A, Mendelson M, Malpani R, Balasegaram M, Charani Eet al., 2021, Shortage of essential antimicrobials: a major challenge to global health security, BMJ Global Health, Vol: 6, Pages: 1-10, ISSN: 2059-7908

The lack of access to safe and effective antimicrobials for human populations is a threat to global health security and a contributor to the emergence and spread of antimicrobial resistance (AMR). The increasingly common shortages of antimicrobials are an additional threat to the emergence of AMR. While the threat of such drug shortages is most acutely experienced in low-income and middle-income settings, their consequences impact the quality and effectiveness of antimicrobials worldwide. Furthermore, there is a need for robustly conducted studies examining the impact of these increasingly prevalent shortages on patient outcomes and on the emergence and spread of AMR. In this review, we have mapped common drivers for antimicrobial shortages and propose strategies for rethinking the regulation, supply and pricing of antimicrobials to secure their sustainable access across diverse healthcare systems and to help minimise the unintended consequences of weak and ineffective supply chains. Greater government involvement in antimicrobial manufacture and supply is essential to ensure no one is left behind. Dedicated demand systems need to be developed for antimicrobials which take into consideration evolving AMR patterns, burden of diseases, pandemic events and supply and demand issues and facilitate implementation of strategies to address them. Interventions, ranging from advocacy and forecasting to public–private collaborations, new economic models and international consortia working across countries and supply chains, will help assure access to safe and effective antimicrobials to all populations around the globe and ensure that shortages no longer contribute to AMR.

Journal article

Miglietta L, Moniri A, Pennisi I, Malpartida-Cardenas K, Abbas H, Hill-Cawthorne K, Bolt F, Jauneikaite E, Davies F, Holmes A, Georgiou P, Rodriguez Manzano Jet al., 2021, Coupling machine learning and high throughput multiplex digital PCR enables accurate detection of carbapenem-resistant genes in clinical isolates, Frontiers in Molecular Biosciences, ISSN: 2296-889X

Journal article

Sangkaew S, Ming D, Boonyasiri A, Honeyford K, Kalayanarooj S, Yacoub S, Dorigatti I, Holmes Aet al., 2021, Transaminases and serum albumin as early predictors of severe dengue - Authors' reply., Lancet Infect Dis, Vol: 21, Pages: 1489-1490

Journal article

Hernandez B, Herrero-Viñas P, Rawson TM, Moore LSP, Holmes A, Georgiou P, Hernandez Perez B, Herrero Viñas P, Rawson TM, Moore LSP, Holmes A, Georgiou Pet al., 2021, Resistance trend estimation using regression analysis to enhance antimicrobial surveillance: a multi-centre study in London 2009-2016, Antibiotics, Vol: 10, Pages: 1-16, ISSN: 2079-6382

In the last years, there has been an increase of antimicrobial resistance rates around the world with the misuse and overuse of antimicrobials as one of the main leading drivers. In response to this threat, a variety of initiatives have arisen to promote the efficient use of antimicrobials. These initiatives rely on antimicrobial surveillance systems to promote appropriate prescription practices and are provided by national or global health care institutions with limited consideration of the variations within hospitals. As a consequence, physicians’ adherence to these generic guidelines is still limited. To fill this gap, this work presents an automated approach to performing local antimicrobial surveillance from microbiology data. Moreover, in addition to the commonly reported resistance rates, this work estimates secular resistance trends through regression analysis to provide a single value that effectively communicates the resistance trend to a wider audience. The methods considered for trend estimation were ordinary least squares regression, weighted least squares regression with weights inversely proportional to the number of microbiology records available and autoregressive integrated moving average. Among these, weighted least squares regression was found to be the most robust against changes in the granularity of the time series and presented the best performance. To validate the results, three case studies have been thoroughly compared with the existing literature: (i) Escherichia coli in urine cultures; (ii) Escherichia coli in blood cultures; and (iii) Staphylococcus aureus in wound cultures. The benefits of providing local rather than general antimicrobial surveillance data of a higher quality is two fold. Firstly, it has the potential to stimulate engagement among physicians to strengthen their knowledge and awareness on antimicrobial resistance which might encourage prescribers to change their prescription habits more willingly. Moreover, it pro

Journal article

Boshier FAT, Venturini C, Stirrup O, Guerra-Assunção JA, Alcolea-Medina A, Becket AH, Byott M, Charalampous T, Filipe ADS, Frampton D, Glaysher S, Khan T, Kulasegara-Shylini R, Kele B, Monahan IM, Mollett G, Parker M, Pelosi E, Randell P, Roy S, Taylor JF, Weller SJ, Wilson-Davies E, Wade P, Williams R, Copas AJ, Cutino-Moguel T, Freemantle N, Hayward AC, Holmes A, Hughes J, Mahungu TW, Nebbia G, Nastouli E, Partridge DG, Pope CF, Price JR, Robson SC, Saeed K, Shin GY, de Silva TI, Snell LB, Thomson EC, Witney AA, Breuer J, COG-UK HOCI Variant Substudy consortium, The COVID-19 Genomics UK COG-UK consortiumet al., 2021, The Alpha variant was not associated with excess nosocomial SARS-CoV-2 infection in a multi-centre UK hospital study., J Infect

OBJECTIVES: Recently emerging SARS-CoV-2 variants have been associated with an increased rate of transmission within the community. We sought to determine whether this also resulted in increased transmission within hospitals. METHODS: We collected viral sequences and epidemiological data of patients with community and healthcare associated SARS-CoV-2 infections, sampled from 16th November 2020 to 10th January 2021, from nine hospitals participating in the COG-UK HOCI study. Outbreaks were identified using ward information, lineage and pairwise genetic differences between viral sequences. RESULTS: Mixed effects logistic regression analysis of 4184 sequences showed healthcare-acquired infections were no more likely to be identified as the Alpha variant than community acquired infections. Nosocomial outbreaks were investigated based on overlapping ward stay and SARS-CoV-2 genome sequence similarity. There was no significant difference in the number of patients involved in outbreaks caused by the Alpha variant compared to outbreaks caused by other lineages. CONCLUSIONS: We find no evidence to support it causing more nosocomial transmission than previous lineages. This suggests that the stringent infection prevention measures already in place in UK hospitals contained the spread of the Alpha variant as effectively as other less transmissible lineages, providing reassurance of their efficacy against emerging variants of concern.

Journal article

Charani E, Holmes A, Bonaconsa C, Mbamalu O, Mendelson M, Surendran S, Singh S, Nampoothiri V, Boutall A, Tarrant C, Dhar P, Pennel T, Leather A, Hampton Met al., 2021, Investigating infection management and antimicrobial stewardship in surgery: a qualitative study from India and South Africa, Clinical Microbiology and Infection, Vol: 27, Pages: 1455-1464, ISSN: 1198-743X

Objectives To investigate the drivers for infection management and antimicrobial stewardship (AMS) across high infection risk surgical pathways. Methods An qualitative study, ethnographic observation of clinical practices, patient case studies, and face-to-face interviews with healthcare professionals (HCP) and patients was conducted across cardiovascular and thoracic and gastrointestinal surgical pathways in South Africa (SA) and India. Aided by Nvivo 11 software, data were coded and analysed until saturation was reached. The multiple modes of enquiry enabled cross-validation and triangulation of findings.Results Between July 2018–August 2019 data were gathered from 190 hours of non-participant observations (138 India, 72 SA); interviews with HCPs (44 India, 61 SA); patients (6 India, 8 SA), and, case studies (4 India, 2 SA). Across the surgical pathway, multiple barriers impede effective infection management and AMS. The existing, implicit roles of HCPs (including nurses, and senior surgeons) are overlooked as interventions target junior doctors, bypassing the opportunity for integrating infection-related care across the surgical team. Critically, the ownership of decisions remains with the operating surgeons and entrenched hierarchies restrict the inclusion of other HCPs in decision-making. The structural foundations to enable staff to change their behaviours and participate in infection-related surgical care is lacking.ConclusionsIdentifying the implicit existing HCPs roles in infection management is critical and will facilitate the development of effective and transparent processes across the surgical team for optimised care. Applying a framework approach that includes nurse leadership, empowering pharmacists and engaging surgical leads is essential for integrated AMS and infection-related care. Keywords: antibiotic prescribing, infection control, ethnography, low- and middle-income country, surgery

Journal article

Zhu J, Holmes A, 2021, Changing patterns of bloodstream infections in the community and acute care across two COVID-19 epidemic waves: a retrospective analysis using data linkage, Clinical Infectious Diseases, ISSN: 1058-4838

BackgroundWe examined the epidemiology of community- and hospital-acquired bloodstream infections (BSIs) in COVID-19 and non-COVID-19 patients across two epidemic waves.MethodsWe analysed blood cultures of patients presenting and admitted to a London hospital group between January 2020 and February 2021. We reported BSI incidence, as well as changes in sampling, case mix, healthcare capacity, and COVID-19 variants.Results34,044 blood cultures were taken. We identified 1,047 BSIs; 653 (62.4%) community-acquired and 394 (37.6%) hospital-acquired. Important changes in patterns were seen. Among community-acquired BSIs, Escherichia coli BSIs remained lower than pre-pandemic level during COVID-19 waves, however peaked following lockdown easing in May 2020, deviating from the historical trend of peaking in August. The hospital-acquired BSI rate was 100.4 per 100,000 patient-days across the pandemic, increasing to 132.3 during the first wave and 190.9 during the second, with significant increase seen in elective inpatients. Patients who developed a hospital-acquired BSI, including those without COVID-19, experienced 20.2 excess days of hospital stay and 26.7% higher mortality, higher than reported in pre-pandemic literature. In intensive care, the BSI rate was 421.0 per 100,000 patient-ICU days during the second wave, compared to 101.3 pre-COVID. The BSI incidence in those infected with the SARS-CoV-2 Alpha variant was similar to that seen with earlier variants.ConclusionsThe pandemic and national responses have impacted the patterns of community- and hospital-acquired BSIs, in COVID-19 and non-COVID-19 patients. Factors driving the observed patterns are complex. Infection surveillance needs to consider key aspects of pandemic response and changes in healthcare access and practice.

Journal article

Rodriguez-Bano J, Maria Rossolini G, Schultsz C, Tacconelli E, Murthy S, Ohmagari N, Holmes A, Bachmann T, Goossens H, Canton R, Roberts AP, Henriques-Normark B, Clancy CJ, Huttner B, Fagerstedt P, Lahiri S, Kaushic C, Hoffman SJ, Warren M, Zoubiane G, Essack S, Laxminarayan R, Plant Let al., 2021, Key considerations on the potential impacts of the COVID-19 pandemic on antimicrobial resistance research and surveillance, TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE, Vol: 115, Pages: 1122-1129, ISSN: 0035-9203

Journal article

Bonaconsa C, Mbamalu O, Mendelson M, Boutall A, Warden C, Rayamajhi S, Pennel T, Hampton M, Joubert I, Tarrant C, Holmes A, Charani Eet al., 2021, Visual mapping of team dynamics and communication patterns on surgical ward rounds: an ethnographic study, BMJ Quality & Safety, Vol: 30, Pages: 812-824, ISSN: 2044-5415

Background: Team dynamics influence infection prevention and management practices and implementation of antibiotic stewardship (AS). Using an innovative visual mapping approach, alongside traditional qualitative methods, we aimed to study team dynamics and flow of communication (who gets to speak, and whose voice is heard) during surgical ward rounds, and how team dynamics and communication patterns may shape decision-making in relation to infection management and AS.Materials/methods: Between May and November 2019, data were gathered through direct observations of ward rounds and face-to-face interviews with ward round participants in selected surgical specialties at a tertiary hospital in South Africa. Using a visual mapping method – sociograms – content and flow of communication and the social links between individual participants were plotted. Field notes from observations and interview transcripts were analysed using a grounded theory approach.Results: Data were gathered from 60 hours of ward round observations, including 1024 individual patient discussions; 60 sociograms, interviews with healthcare professionals (60) and patients (7). The nature of discussions about AS and IPC on ward rounds vary across specialties and are affected by the content and structure of the clinical update provided, the consultant’s leadership and interaction style, and competing priorities at the bedside. Registrars act as gatekeepers, initiating antibiotic discussions; consultants are key decision-makers. Other team members have limited input in ward round conversations, despite having recognised roles in AS and IPC. Hierarchies in teams manifest themselves on ward rounds in where staff position themselves, influencing their contribution to care. Varied leadership styles affect ward-round dynamics, in particular, whether nurses and patients are actively engaged in key decisions on infection management and antibiotic therapy, and whether actions are assigned to i

Journal article

Borek AJ, Campbell A, Dent E, Moore M, Butler CC, Holmes A, Walker AS, McLeod M, Tonkin-Crine S, STEP-UP study teamet al., 2021, Development of an intervention to support the implementation of evidence-based strategies for optimising antibiotic prescribing in general practice., Implement Sci Commun, Vol: 2

BACKGROUND: Trials show that antimicrobial stewardship (AMS) strategies, including communication skills training, point-of-care C-reactive protein testing (POC-CRPT) and delayed prescriptions, help optimise antibiotic prescribing and use in primary care. However, the use of these strategies in general practice is limited and inconsistent. We aimed to develop an intervention to enhance uptake and implementation of these strategies in primary care. METHODS: We drew on the Person-Based Approach to develop an implementation intervention in two stages. (1) Planning and design: We defined the problem in behavioural terms drawing on existing literature and conducting primary qualitative research (nine focus groups) in high-prescribing general practices. We identified 'guiding principles' with intervention objectives and key features and developed logic models representing intended mechanisms of action. (2) Developing the intervention: We created prototype intervention materials and discussed and refined these with input from 13 health professionals and 14 citizens in two sets of design workshops. We further refined the intervention materials following think-aloud interviews with 22 health professionals. RESULTS: Focus groups highlighted uncertainties about how strategies could be used. Health professionals in the workshops suggested having practice champions, brief summaries of each AMS strategy and evidence supporting the AMS strategies, and they and citizens gave examples of helpful communication strategies/phrases. Think-aloud interviews helped clarify and shorten the text and user journey of the intervention materials. The intervention comprised components to support practice-level implementation: antibiotic champions, practice meetings with slides provided, and an 'implementation support' website section, and components to support individual-level uptake: website sections on each AMS strategy (with evidence, instructions, links to electronic resources) and materi

Journal article

Ming DKY, Myall A, Hernandez B, Weisse A, Peach R, Barahona M, Rawson T, Holmes Aet al., 2021, Informing antimicrobial management in the context of COVID-19: understanding the longitudinal dynamics of C-reactive protein and procalcitonin, BMC Infectious Diseases, Vol: 21, ISSN: 1471-2334

Background:To characterise the longitudinal dynamics of C-reactive protein (CRP) and Procalcitonin (PCT) in a cohort of hospitalised patients with COVID-19 and support antimicrobial decision-making.Methods:Longitudinal CRP and PCT concentrations and trajectories of 237 hospitalised patients with COVID-19 were modelled. The dataset comprised of 2,021 data points for CRP and 284 points for PCT. Pairwise comparisons were performed between: (i) those with or without significant bacterial growth from cultures, and (ii) those who survived or died in hospital.Results:CRP concentrations were higher over time in COVID-19 patients with positive microbiology (day 9: 236 vs 123 mg/L, p < 0.0001) and in those who died (day 8: 226 vs 152 mg/L, p < 0.0001) but only after day 7 of COVID-related symptom onset. Failure for CRP to reduce in the first week of hospital admission was associated with significantly higher odds of death. PCT concentrations were higher in patients with COVID-19 and positive microbiology or in those who died, although these differences were not statistically significant.Conclusions:Both the absolute CRP concentration and the trajectory during the first week of hospital admission are important factors predicting microbiology culture positivity and outcome in patients hospitalised with COVID-19. Further work is needed to describe the role of PCT for co-infection. Understanding relationships of these biomarkers can support development of risk models and inform optimal antimicrobial strategies.

Journal article

Stirrup O, Boshier F, Venturini C, Guerra-Assuncao JA, Alcolea-Medina A, Beckett A, Charalampous T, da Silva Filipe A, Glaysher S, Khan T, Kulasegaran Shylini R, Kele B, Monahan I, Mollett G, Parker M, Pelosi E, Randell P, Roy S, Taylor J, Weller S, Wilson-Davies E, Wade P, Williams R, Copas A, Cutino-Moguel M-T, Freemantle N, Hayward AC, Holmes A, Hughes J, Mahungu T, Nebbia G, Partridge D, Pope C, Price J, Robson S, Saeed K, de Silva T, Snell L, Thomson E, Witney AA, Breuer Jet al., 2021, SARS-CoV-2 lineage B.1.1.7 is associated with greater disease severity among hospitalised women but not men: multicentre cohort study, BMJ OPEN RESPIRATORY RESEARCH, Vol: 8, ISSN: 2052-4439

Journal article

Mbamalu O, Bonaconsa C, Nampoothiri V, Surendran S, Veepanattu P, Singh S, Dhar P, Carter V, Boutall A, Pennel T, Hampton M, Holmes A, Mendelson M, Charani Eet al., 2021, Patient understanding of and participation in infection-related care across surgical pathways: a scoping review, INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, Vol: 110, Pages: 123-134, ISSN: 1201-9712

Journal article

Lamb G, Phillips G, Charani E, Holmes A, Satta Get al., 2021, Antibiotic prescribing practices in general surgery: a mixed methods quality improvement project., Infect Prev Pract, Vol: 3

Background: A single pre-operative antibiotic dose provides optimal prophylaxis against surgical site infection (SSI), but significant variability persists in adherence to prophylaxis guidelines. We describe a quality improvement project aiming to improve guideline-driven antibiotic prescribing within surgical teams at a tertiary hospital. Methods: Face-to-face interviews with surgical teams and anonymous surveys of senior surgeons and anaesthetists were used to collect qualitative data on the perceptions and attitudes of prescribers. This informed intervention development, including a daily ward-round checklist using the acronymous 'ABBDDOMM', from A (antibiotics) to M (microbiology), combined with education and heightened guideline accessibility. A first audit cycle was performed for patients undergoing intra-abdominal surgery during a two-month period (cycle one). Post-implementation data were collected 12 months later (cycle two). Findings: Interviews provided insight into common themes and barriers surrounding antibiotic prescribing, whilst surveys explored future solutions to these barriers. In cycle one, 100/205 (48.8%) patients received extended antibiotics beyond the single-dose prophylaxis. Following intervention, only 41/138 (29.7%) patients received extended antibiotic courses, demonstrating a 21.5% reduction in prolonged antibiotics (P<0.0005). In cycle one, 107/205 patients (52.2%) received antibiotics compliant with Trust Guidelines, compared to 80/138 (58.0%) in cycle two. Conclusion: Our proposed checklist, alongside antimicrobial stewardship education, prompts daily review of important patient parameters and results to significantly reduce inappropriate post-operative antibiotic prescribing. Promoting the sustained use of similar checklists by junior doctors and focusing on measures to improve uptake of pre-operative induction antibiotic guidelines is required to achieve further benefits.

Journal article

Hayhoe B, 2021, Public preferences for delayed or immediate antibiotic prescriptions in UK primary care: a choice experiment, PLoS Medicine, Vol: 18, Pages: 1-20, ISSN: 1549-1277

Delayed (or ‘back-up’) antibiotic prescription, where the patient is given a prescription but advised todelay initiating antibiotics, has been shown to be effective in reducing antibiotic use in primary care.However, this strategy is not widely used in the UK. This study aimed to identify factors influencingpreferences among the UK public for delayed prescription, and understand their relative importance,to help increase appropriate use of this prescribing option.Methods and FindingsWe conducted an online choice experiment in two UK general population samples: adults, and parentsof children under 18 years. Respondents were presented with twelve scenarios in which they, or theirchild, might need antibiotics for a respiratory tract infection, and asked to choose either an immediateor a delayed prescription. Scenarios were described by seven attributes. Data were collected betweenNovember 2018 and February 2019. Respondent preferences were modelled using mixed-effectslogistic regression.The survey was completed by 802 adults and 801 parents (75% of those who opened the survey). Thesamples reflected the UK population in age, sex, ethnicity and country of residence. The mostimportant determinant of respondent choice was symptom severity, especially for cough-relatedsymptoms. In the adult sample the probability of choosing delayed prescription was 0.53 (95% CI 0.50-0.56, p<.001) for a chesty cough and runny nose, compared to 0.30 (0.28-0.33, p<.001) for a chestycough with fever, 0.47 (0.44-0.50, p<.001) for sore throat with swollen glands and 0.37 (0.34-0.39,p<.001) for sore throat, swollen glands and fever. Respondents were less likely to choose delayedprescription with increasing duration of illness (odds ratio 0.94 (0.92-0.96, p<0.001)). Probabilities ofchoosing delayed prescription were similar for parents considering treatment for a child (44% ofchoices vs. 42% for adults, p=0.04). However, parents differed from the adult sample in showing

Journal article

Charani E, McKee M, Ahmad R, Balasegaram M, Bonaconsa C, Merrett GB, Busse R, Carter V, Castro-Sanchez E, Franklin BD, Georgiou P, Hill-Cawthorne K, Hope W, Imanaka Y, Kambugu A, Leather AJM, Mbamalu O, McLeod M, Mendelson M, Mpundu M, Rawson TM, Ricciardi W, Rodriguez-Manzano J, Singh S, Tsioutis C, Uchea C, Zhu N, Holmes AHet al., 2021, Optimising antimicrobial use in humans-review of current evidence and an interdisciplinary consensus on key priorities for research, LANCET REGIONAL HEALTH-EUROPE, Vol: 7, ISSN: 2666-7762

Journal article

Petersen E, Lee SS, Blumberg L, Kramer LD, Obiero C, Al-Abri S, Abubakar A, Pinto TCA, Yapi BR, Tambyah PA, Holmes AHet al., 2021, International Journal of Infectious Diseases: from the past quarter-century to the next, INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, Vol: 109, Pages: 36-37, ISSN: 1201-9712

Journal article

Zhu J, Ferlie E, Castro-Sánchez E, Birgand G, Holmes A, Atun R, Kieltyka H, Ahmad Ret al., 2021, Macro level factors influencing strategic responses to emergent pandemics: a scoping review, Journal of Global Health, Vol: 11, Pages: 1-16, ISSN: 2047-2978

Background: Strategic planning is critical for successful pandemic management. This study aimed to identify and review the scope and analytic depth of situation analyses conducted to understand their utility, and capture the documented macro-level factors impacting4pandemic management. Methods: To synthesise this disparate body of literature, we adopted a two-step search and 6review process. A systematic search of the literature was conducted to identify all studies since 2000, that have 1) employed a situation analysis;and2) examined contextual factors influencing pandemic management. The included studies are analysed using a seven-domain systems approach rom the discipline of strategic management. Findings: Nineteen studies were included in the final review ranging from single country (6) to regional, multi-country studies (13). Fourteen studies had a single disease focus, with 5 studies evaluating responses to one or more of COVID-19, Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS),Influenza A (H1N1),Ebola virus disease, and Zika virus disease pandemics. Six studies examined a single domain from political, economic, sociological, technological, ecological or wider industry(PESTELI), 5 studies examined two to four domains, and8studies examined five or more domains. Methods employed were predominantly literature reviews. The recommendations focus predominantly on addressing inhibitors in the sociological and technological domains with few recommendations articulated in the political domain. Overall, the legislative domain is least represented. Conclusions: Ex-post analysis using the seven-domain strategic management framework provides further opportunities for a planned systematic response to pandemics which remains critical as the current COVID-19 pandemic evolves.

Journal article

Ahmad R, Atun R, Birgand G, Castro-Sánchez E, Charani E, Ferlie E, Hussain I, Kambugu A, Labarca J, Levy Hara G, Mckee M, Mendelson M, Singh S, Varma J, Zhu J, Zingg W, Holmes Aet al., 2021, Macro level influences on strategic responses to the COVID-19 pandemic – an international survey and tool for national assessments, Journal of Global Health, Vol: 11, Pages: 1-11, ISSN: 2047-2978

Background Variation in the approaches taken to contain the SARS-CoV-2 (COVID-19) pandemic at country level has been shaped by economic and political considerations, technical capacity, and assumptions about public behaviours. To address the limited application of learning from previous pandemics, this study aimed to analyse perceived facilitators and inhibitors during the pandemic and to inform the development of an assessment tool for pandemic response planning.Methods A cross-sectional electronic survey of health and non-healthcare professionals (5 May - 5 June 2020) in six languages, with respondents recruited via email, social media and website posting. Participants were asked to score inhibitors (-10 to 0) or facilitators (0 to +10) impacting country response to COVID-19 from the following domains – Political, Economic, Sociological, Technological, Ecological, Legislative, and wider Industry (the PESTELI framework). Participants were then asked to explain their responses using free text. Descriptive and thematic analysis was followed by triangulation with the literature and expert validation to develop the assessment tool, which was then compared with four existing pandemic planning frameworks.Results 928 respondents from 66 countries (57% healthcare professionals) participated. Political and economic influences were consistently perceived as powerful negative forces and technology as a facilitator across high- and low-income countries. The 103-item tool developed for guiding rapid situational assessment for pandemic planning is comprehensive when compared to existing tools and highlights the interconnectedness of the 7 domains. Conclusions The tool developed and proposed addresses the problems associated with decision making in disciplinary silos and offers a means to refine future use of epidemic modelling.

Journal article

Sangkaew S, Ming D, Boonyasiri A, Honeyford K, Kalayanarooj S, Yacoub S, Dorigatti I, Holmes Aet al., 2021, Risk predictors of progression to severe disease during the febrile phase of dengue: a systematic review and meta-analysis, Lancet Infectious Diseases, Vol: 21, Pages: 1014-1026, ISSN: 1473-3099

BACKGROUND: The ability to accurately predict early progression of dengue to severe disease is crucial for patient triage and clinical management. Previous systematic reviews and meta-analyses have found significant heterogeneity in predictors of severe disease due to large variation in these factors during the time course of the illness. We aimed to identify factors associated with progression to severe dengue disease that are detectable specifically in the febrile phase. METHODS: We did a systematic review and meta-analysis to identify predictors identifiable during the febrile phase associated with progression to severe disease defined according to WHO criteria. Eight medical databases were searched for studies published from Jan 1, 1997, to Jan 31, 2020. Original clinical studies in English assessing the association of factors detected during the febrile phase with progression to severe dengue were selected and assessed by three reviewers, with discrepancies resolved by consensus. Meta-analyses were done using random-effects models to estimate pooled effect sizes. Only predictors reported in at least four studies were included in the meta-analyses. Heterogeneity was assessed using the Cochrane Q and I2 statistics, and publication bias was assessed by Egger's test. We did subgroup analyses of studies with children and adults. The study is registered with PROSPERO, CRD42018093363. FINDINGS: Of 6643 studies identified, 150 articles were included in the systematic review, and 122 articles comprising 25 potential predictors were included in the meta-analyses. Female patients had a higher risk of severe dengue than male patients in the main analysis (2674 [16·2%] of 16 481 vs 3052 [10·5%] of 29 142; odds ratio [OR] 1·13 [95% CI 1·01-1·26) but not in the subgroup analysis of studies with children. Pre-existing comorbidities associated with severe disease were diabetes (135 [31·3%] of 431 with vs 868 [16·0%] of 5421 witho

Journal article

Rawson TM, Wilson RC, O'Hare D, Herrero P, Kambugu A, Lamorde M, Ellington M, Georgiou P, Cass A, Hope WW, Holmes AHet al., 2021, Optimizing antimicrobial use: challenges, advances and opportunities, NATURE REVIEWS MICROBIOLOGY, ISSN: 1740-1526

Journal article

Rawson TM, Hernandez B, Moore L, Herrero P, Charani E, Ming D, Wilson R, Blandy O, Sriskandan S, Toumazou C, Georgiou P, Holmes Aet al., 2021, A real-world evaluation of a case-based reasoning algorithm to support antimicrobial prescribing decisions in acute care, Clinical Infectious Diseases, Vol: 72, Pages: 2103-2111, ISSN: 1058-4838

BackgroundA locally developed Case-Based Reasoning (CBR) algorithm, designed to augment antimicrobial prescribing in secondary care was evaluated.MethodsPrescribing recommendations made by a CBR algorithm were compared to decisions made by physicians in clinical practice. Comparisons were examined in two patient populations. Firstly, in patients with confirmed Escherichia coli blood stream infections (‘E.coli patients’), and secondly in ward-based patients presenting with a range of potential infections (‘ward patients’). Prescribing recommendations were compared against the Antimicrobial Spectrum Index (ASI) and the WHO Essential Medicine List Access, Watch, Reserve (AWaRe) classification system. Appropriateness of a prescription was defined as the spectrum of the prescription covering the known, or most-likely organism antimicrobial sensitivity profile.ResultsIn total, 224 patients (145 E.coli patients and 79 ward patients) were included. Mean (SD) age was 66 (18) years with 108/224 (48%) female gender. The CBR recommendations were appropriate in 202/224 (90%) compared to 186/224 (83%) in practice (OR: 1.24 95%CI:0.392-3.936;p=0.71). CBR recommendations had a smaller ASI compared to practice with a median (range) of 6 (0-13) compared to 8 (0-12) (p<0.01). CBR recommendations were more likely to be classified as Access class antimicrobials compared to physicians’ prescriptions at 110/224 (49%) vs. 79/224 (35%) (OR: 1.77 95%CI:1.212-2.588 p<0.01). Results were similar for E.coli and ward patients on subgroup analysis.ConclusionsA CBR-driven decision support system provided appropriate recommendations within a narrower spectrum compared to current clinical practice. Future work must investigate the impact of this intervention on prescribing behaviours more broadly and patient outcomes.

Journal article

Rodriguez-Bano J, Rossolini GM, Schultsz C, Tacconelli E, Murthy S, Ohmagari N, Holmes A, Bachmann T, Goossens H, Canton R, Roberts AP, Henriques-Normark B, Clancy CJ, Huttner B, Fagerstedt P, Lahiri S, Kaushic C, Hoffman SJ, Warren M, Zoubiane G, Essack S, Laxminarayan R, Plant Let al., 2021, Antimicrobial resistance research in a post-pandemic world: Insights on antimicrobial resistance research in the COVID-19 pandemic, JOURNAL OF GLOBAL ANTIMICROBIAL RESISTANCE, Vol: 25, Pages: 5-7, ISSN: 2213-7165

Journal article

Myall AC, Peach RL, Weiße AY, Davies F, Mookerjee S, Holmes A, Barahona Met al., 2021, Network memory in the movement of hospital patients carrying drug-resistant bacteria, Applied Network Science, Vol: 6, ISSN: 2364-8228

Hospitals constitute highly interconnected systems that bring into contact anabundance of infectious pathogens and susceptible individuals, thus makinginfection outbreaks both common and challenging. In recent years, there hasbeen a sharp incidence of antimicrobial-resistance amongsthealthcare-associated infections, a situation now considered endemic in manycountries. Here we present network-based analyses of a data set capturing themovement of patients harbouring drug-resistant bacteria across three largeLondon hospitals. We show that there are substantial memory effects in themovement of hospital patients colonised with drug-resistant bacteria. Suchmemory effects break first-order Markovian transitive assumptions andsubstantially alter the conclusions from the analysis, specifically on noderankings and the evolution of diffusive processes. We capture variable lengthmemory effects by constructing a lumped-state memory network, which we then useto identify overlapping communities of wards. We find that these communities ofwards display a quasi-hierarchical structure at different levels of granularitywhich is consistent with different aspects of patient flows related to hospitallocations and medical specialties.

Journal article

Zhu N, Aylin P, Rawson T, Gilchrist M, Majeed A, Holmes Aet al., 2021, Investigating the impact of COVID-19 on primary care antibiotic prescribing in North West London across two epidemic waves, Clinical Microbiology and Infection, Vol: 27, Pages: 762-768, ISSN: 1198-743X

ObjectivesWe investigated the impact of COVID-19 and national pandemic response on primary care antibiotic prescribing in London.MethodsIndividual prescribing records between 2015 and 2020 for 2 million residents in north west London were analysed. Prescribing records were linked to SARS-CoV-2 test results. Prescribing volumes, in total, and stratified by patient characteristics, antibiotic class and AWaRe classification, were investigated. Interrupted time series analysis was performed to detect measurable change in the trend of prescribing volume since the national lockdown in March 2020, immediately before the first COVID-19 peak in London.ResultsRecords covering 366 059 patients, 730 001 antibiotic items and 848 201 SARS-CoV-2 tests between January and November 2020 were analysed. Before March 2020, there was a background downward trend (decreasing by 584 items/month) in primary care antibiotic prescribing. This reduction rate accelerated to 3504 items/month from March 2020. This rate of decrease was sustained beyond the initial peak, continuing into winter and the second peak. Despite an overall reduction in prescribing volume, co-amoxiclav, a broad-spectrum “Access” antibiotic, prescribing rose by 70.1% in patients aged 50 and older from February to April. Commonly prescribed antibiotics within 14 days of a positive SARS-CoV-2 test were amoxicillin (863/2474, 34.9%) and doxycycline (678/2474, 27.4%). This aligned with national guidelines on management of community pneumonia of unclear cause. The proportion of “Watch” antibiotics used decreased during the peak in COVID-19.DiscussionA sustained reduction in community antibiotic prescribing has been observed since the first lockdown. Investigation of community-onset infectious diseases and potential unintended consequences of reduced prescribing is urgently needed.

Journal article

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