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

261 results found

Otter JA, Mookerjee S, Davies F, Bolt F, Dyakova E, Shersing Y, Boonyasiri A, Weiße AY, Gilchrist M, Galletly TJ, Brannigan ET, Holmes AHet al., 2020, Detecting carbapenemase-producing Enterobacterales (CPE): an evaluation of an enhanced CPE infection control and screening programme in acute care., J Antimicrob Chemother

OBJECTIVES: The transmission of carbapenemase-producing Enterobacterales (CPE) poses an increasing healthcare challenge. A range of infection prevention activities, including screening and contact precautions, are recommended by international and national guidelines. We evaluated the introduction of an enhanced screening programme in a multisite London hospital group. METHODS: In June 2015, an enhanced CPE policy was launched in response to a local rise in CPE detection. This increased infection prevention measures beyond the national recommendations, with enhanced admission screening, contact tracing and environmental disinfection, improved laboratory protocols and staff/patient education. We report the CPE incidence and trends of CPE in screening and clinical cultures and the adoption of enhanced CPE screening. All non-duplicate CPE isolates identified between April 2014 and March 2018 were included. RESULTS: The number of CPE screens increased progressively, from 4530 in July 2015 to 10 589 in March 2018. CPE detection increased from 18 patients in July 2015 (1.0 per 1000 admissions) to 50 patients in March 2018 (2.7 per 1000 admissions). The proportion of CPE-positive screening cultures remained at approximately 0.4% throughout, suggesting that whilst the CPE carriage rate was unchanged, carrier identification increased. Also, 123 patients were identified through positive CPE clinical cultures over the study period; there was no significant change in the rate of CPE from clinical cultures per 1000 admissions (P = 0.07). CONCLUSIONS: Our findings suggest that whilst the enhanced screening programme identified a previously undetected reservoir of CPE colonization in our patient population, the rate of detection of CPE in clinical cultures did not increase.

Journal article

Ming DK, Sorawat S, Chanh HQ, Nhat PTH, Yacoub S, Georgiou P, Holmes AHet al., 2020, Continuous physiological monitoring using wearable technology to inform individual management of infectious diseases, public health and outbreak responses, International Journal of Infectious Diseases, ISSN: 1201-9712

Optimal management of infectious diseases is guided by up-to-date information at the individual and public health level. For infections of global importance including emerging pandemics such as COVID-19 or prevalent endemic diseases such like dengue, identifying patients at risk of severe disease and clinical deterioration can be challenging given the majority present with a mild illness. In our article, we describe the use of wearable technology for continuous physiological monitoring in healthcare. Deployment of wearables in hospital settings for the management of infectious diseases, or in the community to support syndromic surveillance during outbreaks could provide significant, cost effective advantages and improve healthcare delivery. We highlight a range of promising technologies employed by wearable devices and discuss the technical and ethical issues relating to implementation in the clinic, with specific focus on low- and middle- income countries. Finally, we propose a set of essential criteria for the roll-out of wearable technology for clinical use.

Journal article

Peiffer-Smadja N, Rawson TM, Ahmad R, Buchard A, Georgiou P, Lescure F-X, Birgand G, Holmes AHet al., 2020, Corrigendum to 'Machine learning for clinical decision support in infectious diseases: A narrative review of current applications'Clinical Microbiology and Infection (2020) 584-595., Clin Microbiol Infect

Journal article

Rodriguez Manzano J, Moser N, Malpartida Cardenas K, Moniri A, Fisarova L, Pennisi I, Boonyasiri A, Jauneikaite E, Abdolrasouli A, Otter J, Bolt F, Davies F, Didelot X, Holmes A, Georgiou Pet al., 2020, Rapid detection of mobilized colistin resistance using a nucleic acid based lab-on-a-chip diagnostic system, Scientific Reports, Vol: 10, ISSN: 2045-2322

The increasing prevalence of antimicrobial resistance is a serious threat to global public health. One of the most concerning trends is the rapid spread of Carbapenemase-Producing Organisms (CPO), where colistin has become the last-resort antibiotic treatment. The emergence of colistin resistance, including the spread of mobilized colistin resistance (mcr) genes, raises the possibility of untreatable bacterial infections and motivates the development of improved diagnostics for the detection of colistin-resistant organisms. This work demonstrates a rapid response for detecting the most recently reported mcr gene, mcr−9, using a portable and affordable lab-on-a-chip (LoC) platform, offering a promising alternative to conventional laboratory-based instruments such as real-time PCR (qPCR). The platform combines semiconductor technology, for non-optical real-time DNA sensing, with a smartphone application for data acquisition, visualization and cloud connectivity. This technology is enabled by using loop-mediated isothermal amplification (LAMP) as the chemistry for targeted DNA detection, by virtue of its high sensitivity, specificity, yield, and manageable temperature requirements. Here, we have developed the first LAMP assay for mcr−9 - showing high sensitivity (down to 100 genomic copies/reaction) and high specificity (no cross-reactivity with other mcr variants). This assay is demonstrated through supporting a hospital investigation where we analyzed nucleic acids extracted from 128 carbapenemase-producing bacteria isolated from clinical and screening samples and found that 41 carried mcr−9 (validated using whole genome sequencing). Average positive detection times were 6.58 ± 0.42 min when performing the experiments on a conventional qPCR instrument (n = 41). For validating the translation of the LAMP assay onto a LoC platform, a subset of the samples were tested (n = 20), showing average detection times o

Journal article

Rawson TM, Moore L, Castro Sanchez E, Charani E, Davies F, Satta G, Ellington M, Holmes Aet al., 2020, COVID-19 and the potential long term impact on antimicrobial resistance, Journal of Antimicrobial Chemotherapy, ISSN: 0305-7453

The emergence of the SARS-CoV-2 respiratory virus has required an unprecedented response to control the spread of the infection and protect the most vulnerable within society. Whilst the pandemic has focused society on the threat of emerging infections and hand hygiene, certain infection control and antimicrobial stewardship policies may have to be relaxed. It is unclear whether the unintended consequences of these changes will have a net-positive or -negative impact on rates of antimicrobial resistance. Whilst the urgent focus must be on allaying this pandemic, sustained efforts to address the longer-term global threat of antimicrobial resistance should not be overlooked.

Journal article

Rawson TM, Moore L, Zhu N, Ranganathan N, Skolimowska K, Gilchrist M, Satta G, Cooke G, Holmes Aet al., 2020, Bacterial and fungal co-infection in individuals with coronavirus: A rapid review to support COVID-19 antimicrobial prescribing, Clinical Infectious Diseases, ISSN: 1058-4838

BackgroundTo explore and describe the current literature surrounding bacterial/fungal co-infection in patients with coronavirus infection.MethodsMEDLINE, EMBASE, and Web of Science were searched using broad based search criteria relating to coronavirus and bacterial co-infection. Articles presenting clinical data for patients with coronavirus infection (defined as SARS-1, MERS, SARS-COV-2, and other coronavirus) and bacterial/fungal co-infection reported in English, Mandarin, or Italian were included. Data describing bacterial/fungal co-infections, treatments, and outcomes were extracted. Secondary analysis of studies reporting antimicrobial prescribing in SARS-COV-2 even in the absence of co-infection was performed.Results1007 abstracts were identified. Eighteen full texts reported bacterial/fungal co-infection were included. Most studies did not identify or report bacterial/fungal coinfection (85/140;61%). 9/18 (50%) studies reported on COVID-19, 5/18 (28%) SARS-1, 1/18 (6%) MERS, and 3/18 (17%) other coronavirus.For COVID-19, 62/806 (8%) patients were reported as experiencing bacterial/fungal co-infection during hospital admission. Secondary analysis demonstrated wide use of broad-spectrum antibacterials, despite a paucity of evidence for bacterial coinfection. On secondary analysis, 1450/2010 (72%) of patients reported received antimicrobial therapy. No antimicrobial stewardship interventions were described.For non-COVID-19 cases bacterial/fungal co-infection was reported in 89/815 (11%) of patients. Broad-spectrum antibiotic use was reported.ConclusionsDespite frequent prescription of broad-spectrum empirical antimicrobials in patients with coronavirus associated respiratory infections, there is a paucity of data to support the association with respiratory bacterial/fungal co-infection. Generation of prospective evidence to support development of antimicrobial policy and appropriate stewardship interventions specific for the COVID-19 pandemic are urgently requi

Journal article

Petersen E, Wasserman S, Lee S-S, Go U, Holmes AH, Al-Abri S, McLellan S, Blumberg L, Tambyah Pet al., 2020, COVID-19-We urgently need to start developing an exit strategy., Int J Infect Dis, Vol: 96, Pages: 233-239

AIM: The purpose of this perspective is to review the options countries have to exit the draconian "lockdowns" in a carefully staged manner. METHODS: Experts from different countries experiencing Corona Virus Infectious Disease 2019 (COVID-19) reviewed evidence and country-specific approaches and the results of their interventions. RESULTS: Three factors are essential: 1. Reintroduction from countries with ongoing community transmission; 2. The need for extensive testing capacity and widespread community testing, and 3. An adequate supply of personal protective equipment, PPE, to protect health care workers. Discussed at length are lifting physical distancing, how to open manufacturing and construction, logistics, and the opening of higher educational institutions and schools. The use of electronic surveillance is considered. CONCLUSION: Each country should decide on the best path forward. However, we can learn from each other, and the approaches are, in reality, very similar.

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., 2020, A real-world evaluation of a Case-Based Reasoning algorithm to support antimicrobial prescribing decisions in acute care, Clinical Infectious Diseases, 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

Birgand G, Troughton R, Mariano V, Hettiaratchy S, Hopkins S, Otter JA, Holmes Aet al., 2020, How do surgeons feel about the “Getting it Right First Time” national audit? Results from a qualitative assessment., Journal of Hospital Infection, Vol: 104, Pages: 328-331, ISSN: 0195-6701

The implementation of thenational“Getting It Right First Time” (GIRFT)was assessed by interviewing six surgeonsinvolvedat various levelsinsurgical site infection (SSI) audit.The positive impacts were to create new professional collaboration, improve stakeholder engagement, and increase the profile of SSIs. One particular knowledgegap highlighted was that some participantshad been unaware until that point of the criteria for diagnosing an SSI. The quality of data collected was felt poor due to methodological flaws. The audit was described as highly time-consuming and unsustainableif leaning on junior surgeons, without protectedtimeanddesignatedresponsibility.

Journal article

Cogen JD, Kahl BC, Maples H, McColley SA, Roberts JA, Winthrop KL, Morris AM, Holmes A, Flume PA, VanDevanter DR, Waters V, Muhlebach MS, Elborn JS, Saiman L, Bell SC, Antimicrobial Resistance International Working Group in Cystic Fibrosiset al., 2020, Finding the relevance of antimicrobial stewardship for cystic fibrosis., J Cyst Fibros

Antimicrobials have undoubtedly improved the lives of people with CF, but important antimicrobial-related toxicities and the emergence of antimicrobial-resistant bacteria associated with their use must be considered. Antimicrobial stewardship (AMS) is advocated across the spectrum of healthcare to promote the appropriate use of antimicrobials to preserve their current effectiveness and to optimise treatment, and it is clear that AMS strategies are applicable to and can benefit both non-CF and CF populations. This perspective explores the definition and components of an AMS program, the current evidence for AMS, and the reasons why AMS is a challenging concept in the provision of CF care. We also discuss the elements of CF care which align with AMS programs and principles and propose research priorities for AMS in CF.

Journal article

Birgand G, Mutters NT, Ahmad R, Tacconelli E, Lucet J-C, Holmes Aet al., 2020, Risk perception of the antimicrobial resistance by infection control specialists in Europe: a case-vignette study, Antimicrobial Resistance and Infection Control, Vol: 9, ISSN: 2047-2994

BackgroundUsing case-vignettes, we assessed the perception of European infection control (IC) specialists regarding the individual and collective risk associated with antimicrobial resistance (AMR) among inpatients.MethodsIn this study, sixteen case-vignettes were developed to simulate hospitalised patient scenarios in the field of AMR and IC. A total of 245 IC specialists working in different hospitals from 15 European countries were contacted, among which 149 agreed to participate in the study. Using an online database, each participant scored five randomly-assigned case-vignettes, regarding the perceived risk associated with six different multidrug resistant organisms (MDRO). The intra-class correlation coefficient (ICC), varying from 0 (poor) to 1 (perfect), was used to assess the agreement for the risk on a 7-point Likert scale. High risk and low/neutral risk scorers were compared regarding their national, organisational and individual characteristics.ResultsBetween January and May 2017, 149 participants scored 655 case-vignettes. The perceptions of the individual (clinical outcome) and collective (spread) risks were consistently lower than other MDRO for extended spectrum beta-lactamase producing Enterobacteriaceae cases and higher for carbapenemase producing Enterobacteriaceae (CPE) cases. Regarding CPE cases, answers were influenced more by the resistance pattern (93%) than for other MDRO. The risk associated with vancomycin resistant Enterococci cases was considered higher for the collective impact than for the individual outcome (63% vs 40%). The intra-country agreement regarding the individual risk was globally poor varying from 0.00 (ICC: 0–0.25) to 0.51 (0.18–0.85). The overall agreement across countries was poor at 0.20 (0.07–0.33). IC specialists working in hospitals preserved from MDROs perceived a higher individual (local, p = 0.01; national, p < 0.01) and collective risk (local and national p 

Journal article

Honeyford C, Cooke G, Kinderlerer A, Williamson E, Gilchrist M, Holmes A, Glampson B, Mulla A, Costelloe Cet al., 2020, Evaluating a digital sepsis alert in a London multi-site hospital network: a natural experiment using electronic health record data, Journal of the American Medical Informatics Association, Vol: 27, Pages: 274-283, ISSN: 1067-5027

Objective: To determine the impact of a digital sepsis alert on patient outcomes in a UK multi-site hospital network. Methods:A natural experiment utilising the phased introduction (without randomisation) of a digital sepsis alert into a multi-site hospital network. Sepsis alerts were either visible to clinicans (patients in the ‘intervention’ group) or running silently and not visible (the control group). Inverse probability of treatment weighted multivariable logistic regression was used to estimate the effect of the intervention on individual patient outcomes.Outcomes:In-hospital 30-day mortality (all inpatients), prolonged hospital stay (≥7 days) and timely antibiotics (≤60minutes of the alert) for patients who alerted in the Emergency Department. Results: The introduction of the alert was associated with lower odds of death (OR:0.76; 95%CI:(0.70, 0.84) n=21183); lower odds of prolonged hospital stay ≥7 days (OR:0.93; 95%CI:(0.88, 0.99) n=9988); and in patients who required antibiotics, an increased odds of receiving timely antibiotics (OR:1.71; 95%CI:(1.57, 1.87) n=4622).Discussion: Current evidence that digital sepsis alerts are effective is mixed. In this large UK study a digital sepsis alert has been shown to be associated with improved outcomes, including timely antibiotics. It is not known whether the presence of alerting is responsible for improved outcomes, or whether the alert acted as a useful driver for quality improvement initiatives.Conclusions: These findings strongly suggest that the the introduction of a network-wide digital sepsis alert is associated with improvements in patient outcomes, demonstrating that digital based interventions can be successfully introduced and readily evaluated.

Journal article

Ellington MJ, Davies F, Jauneikaite E, Hopkins KL, Turton JF, Adams G, Pavlu J, Innes AJ, Eades C, Brannigan ET, Findlay J, White L, Bolt F, Kadhani T, Chow Y, Patel B, Mookerjee S, Otter JA, Sriskandan S, Woodford N, Holmes Aet al., 2019, A multi-species cluster of GES-5 carbapenemase producing Enterobacterales linked by a geographically disseminated plasmid, Clinical Infectious Diseases, ISSN: 1058-4838

BACKGROUND: 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.

Journal article

Waters VJ, Kidd TJ, Canton R, Ekkelenkamp MB, Johansen HK, LiPuma JJ, Bell SC, Elborn JS, Flume PA, VanDevanter DR, Gilligan P, Bullington W, Burgel P-R, Byrnes C, Drevinek P, Holmes A, Kahl B, Maples H, Martiniano S, McColley S, Morris A, Muhlebach M, Parkins M, Ratjen F, Roberts J, Saiman L, Shah A, Smyth A, Somayaji R, Taccetti G, Tunney M, Winthrop K, Zemanick Eet al., 2019, Reconciling Antimicrobial Susceptibility Testing and Clinical Response in Antimicrobial Treatment of Chronic Cystic Fibrosis Lung Infections, CLINICAL INFECTIOUS DISEASES, Vol: 69, Pages: 1812-1816, ISSN: 1058-4838

Journal article

Honeyford K, Cooke GS, Kinderlerer A, Williamson E, Gilchrist M, Holmes A, Glampson B, Mulla A, Costelloe Cet al., 2019, Evaluating a digital sepsis alert in a multi-site hospital: a natural experiment, Publisher: OXFORD UNIV PRESS, ISSN: 1101-1262

Conference paper

Rawson TM, Gowers SAN, Freeman DME, Wilson RC, Sharma S, Gilchrist M, MacGowan A, Lovering A, Bayliss M, Kyriakides M, Georgiou P, Cass AEG, O'Hare D, Holmes AHet al., 2019, Microneedle biosensors for real-time, minimally invasive drug monitoring of phenoxymethylpenicillin: a first-in-human evaluation in healthy volunteers, The Lancet Digital Health, Vol: 1, Pages: e335-e343, ISSN: 2589-7500

BackgroundEnhanced methods of drug monitoring are required to support the individualisation of antibiotic dosing. We report the first-in-human evaluation of real-time phenoxymethylpenicillin monitoring using a minimally invasive microneedle-based β-lactam biosensor in healthy volunteers.MethodsThis first-in-human, proof-of-concept study was done at the National Institute of Health Research/Wellcome Trust Imperial Clinical Research Facility (Imperial College London, London, UK). The study was approved by London-Harrow Regional Ethics Committee. Volunteers were identified through emails sent to a healthy volunteer database from the Imperial College Clinical Research Facility. Volunteers, who had to be older than 18 years, were excluded if they had evidence of active infection, allergies to penicillin, were at high risk of skin infection, or presented with anaemia during screening. Participants wore a solid microneedle β-lactam biosensor for up to 6 h while being dosed at steady state with oral phenoxymethylpenicillin (five 500 mg doses every 6 h). On arrival at the study centre, two microneedle sensors were applied to the participant's forearm. Blood samples (via cannula, at −30, 0, 10, 20, 30, 45, 60, 90, 120, 150, 180, 210, 240 min) and extracellular fluid (ECF; via microdialysis, every 15 min) pharmacokinetic (PK) samples were taken during one dosing interval. Phenoxymethylpenicillin concentration data obtained from the microneedles were calibrated using locally estimated scatter plot smoothing and compared with free-blood and microdialysis (gold standard) data. Phenoxymethylpenicillin PK for each method was evaluated using non-compartmental analysis. Area under the concentration–time curve (AUC), maximum concentration, and time to maximum concentration were compared. Bias and limits of agreement were investigated with Bland–Altman plots. Microneedle biosensor limits of detection were estimated. The study was registered with ClinicalTria

Journal article

Limmathurotsakul D, Dunachie S, Fukuda K, Feasey NA, Okeke IN, Holmes AH, Moore CE, Dolecek C, van Doorn HR, Shetty N, Lopez AD, Peacock SJet al., 2019, Improving the estimation of the global burden of antimicrobial resistant infections, LANCET INFECTIOUS DISEASES, Vol: 19, Pages: E392-E398, ISSN: 1473-3099

Journal article

Maraolo AE, Ong DSY, Cimen C, Howard P, Kofteridis DP, Schouten J, Mutters NT, Pulcini Cet al., 2019, Organization and training at national level of antimicrobial stewardship and infection control activities in Europe: an ESCMID cross-sectional survey, European Journal of Clinical Microbiology & Infectious Diseases, Vol: 38, Pages: 2061-2068, ISSN: 0934-9723

Antimicrobial stewardship (AMS) and Infection prevention and control (IPC) are two key complementary strategies that combat development and spread of antimicrobial resistance. The ESGAP (ESCMID Study Group for AMS), EUCIC (European Committee on Infection Control) and TAE (Trainee Association of ESCMID) investigated how AMS and IPC activities and training are organized, if present, at national level in Europe. From February 2018 to May 2018, an internet-based cross-sectional survey was conducted through a 36-item questionnaire, involving up to three selected respondents per country, from 38 European countries in total (including Israel), belonging to the ESGAP/EUCIC/TAE networks. All 38 countries participated with at least one respondent, and a total of 81 respondents. Education and involvement in AMS programmes were mandatory during the postgraduate training of clinical microbiology and infectious diseases specialists in up to one-third of countries. IPC was acknowledged as a specialty in 32% of countries. Only 32% of countries had both guidance and national requirements regarding AMS programmes, in contrast to 61% for IPC. Formal national staffing standards for AMS and IPC hospital-based activities were present in 24% and 63% of countries, respectively. The backgrounds of professionals responsible for AMS and IPC programmes varied tremendously between countries. The organization and training of AMS and IPC in Europe are heterogeneous and national requirements for activities are frequently lacking.

Journal article

Zemanick E, Burgel P-R, Taccetti G, Holmes A, Ratjen F, Byrnes CA, Waters VJ, Bell SC, VanDevanter DR, Stuart Elborn J, Flume PA, Antimicrobial Resistance International Working Group in Cystic Fibrosiset al., 2019, Antimicrobial resistance in cystic fibrosis: a Delphi approach to defining best practices, Journal of Cystic Fibrosis, ISSN: 1569-1993

BACKGROUND: Antimicrobial susceptibility testing (AST) is a cornerstone of infection management in cystic fibrosis. However, there is little evidence that AST predicts the clinical outcome of CF antimicrobial treatment. It has been suggested there is a need for careful consideration of current AST use by the CF community. METHODS: We engaged a group of experts consisting of pulmonary (adult and pediatric) and infectious disease clinicians, microbiologists, and pharmacists representing a broad international experience. We conducted an iterative systematic survey (Delphi) to determine and quantify consensus regarding key questions facing CF clinicians in the use of respiratory culture results including what tests to order, when to obtain them, and how to act upon the results of the testing. RESULTS: Consensus was reached for many questions but there was not universal agreement to the questions that were addressed. There were some differences with respect to cultures obtained for surveillance compared to when there is clinical worsening. Areas of general consensus include when and how respiratory cultures should be performed, what information should be reported, and when AST should be performed. A key finding is that clinical response to treatment is used to guide treatment decisions rather than AST results. CONCLUSIONS: Recommendations are presented regarding questions related to microbiology testing for patients with CF. We have also offered recommendations for priority research questions.

Journal article

Castro Sanchez E, Gilchrist M, Ahmad R, Courtenay M, Bosanquet J, Holmes Aet al., 2019, Nurse roles in antimicrobial stewardship: lessons from public sectors models of acute care service delivery in the United Kingdom, Antimicrobial Resistance and Infection Control, Vol: 8, ISSN: 2047-2994

BackgroundHealth care services must engage all relevant healthcare workers, including nurses, inoptimal antimicrobial use to address the global threat of drug-resistant infections. Reflectingupon the variety of antimicrobial stewardship (AMS) nursing models already implemented inthe UK could facilitate policymaking and decisions in other settings about context-sensitive,pragmatic nurse roles.MethodsWe describe purposefully selected cases drawn from the UK network of public sector nursesin AMS exploring their characteristics, influence, relations with clinical and financialstructures, and role content.ResultsAMS nursing has been deployed in the UK within ‘vertical’, ‘horizontal’ or ‘hybrid’ models.The ‘vertical’ model refers to a novel, often unique consultant-type role ideally suited totransform organisational practice by legitimising nurse participation in antimicrobialdecisions. Such organisational improvements may not be straightforward, though, due toscalability issues. The ‘horizontal’ model can foster coordinated efforts to increase optimalAMS behaviours in all nurses around a narrative of patient safety and quality. Such modelmay be unable to address tensions between the required institutional response to sepsis andthe inappropriate use of antibiotics. Finally, the ‘hybrid’ model would increase AMSresponsibilities for all nurses whilst allocating some expanded AMS skills to existing teams ofspecialists such as sepsis or vascular access nurses. This model can generate economiesof scale, yet it may be threatened by a lack of clarity about a nurse-relevant vision.ConclusionsA variety of models articulating the participation of nurses in antimicrobial stewardship effortshave already been implemented in public sector organisations in the UK. The strengths andweaknesses of each model need considering before implementation in other settings andhealthcare systems, including precise metrics of suc

Journal article

Bulabula ANH, Holmes A, Lassmann B, 2019, International Society for Infectious Diseases - First series of position papers, with a focus on implementing infection prevention and control measures in low- and middle-income settings, INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, Vol: 87, Pages: 30-31, ISSN: 1201-9712

Journal article

Charani E, DeBarra E, Gill D, Rawson T, Gilchrist M, Naylor N, Holmes Aet al., 2019, Antibiotic prescribing in general medical and surgical specialties: a prospective cohort study, Antimicrobial Resistance and Infection Control, Vol: 8, Pages: 1-10, ISSN: 2047-2994

Background: Qualitative work has described the differences in prescribing practice across medical and surgical specialties. This study aimed to understand if specialty impacts quantitative measures of prescribing practice. Methods: We prospectively analysed the antibiotic prescribing across general medical and surgical teams for acutely admitted patients. Over a 12-month period (June 2016 – May 2017) 659 patients (362 medical, 297 surgical) were followed for the duration of their hospital stay. Antibiotic prescribing across these cohorts was assessed using Chi-squared or Wilcoxon rank-sum, depending on normality of data. The t-test was used to compare age and length of stay. A logistic regression model was used to predict escalation of antibiotic therapy. Results: Surgical patients were younger (p<0.001) with lower Charlson Comorbidity Index scores (p<0.001). Antibiotics were prescribed for 45% (162/362) medical and 55% (164/297) surgical patients. Microbiological results were available for 26% (42/164) medical and 29% (48/162) surgical patients, of which 55% (23/42) and 48% (23/48) were positive respectively. There was no difference in the spectrum of antibiotics prescribed between surgery and medicine (p=0.507). In surgery antibiotics were 1) prescribed more frequently (p=0.001); 2) for longer (p=0.016); 3) more likely to be escalated (p=0.004); 4) less likely to be compliant with local policy (p<0.001) than medicine. Conclusions: Across both specialties, microbiology investigation results are not adequately used to diagnose infections and optimise their management. There is significant variation in antibiotic decision-making (including escalation patterns) between general surgical and medical teams. Antibiotic stewardship interventions targeting surgical specialties need to go beyond surgical prophylaxis. It is critical to focus on of review the patients initiated on therapeutic antibiotics in surgical specialties to ensure that escalation and c

Journal article

Ahmad R, Zhu NJ, Leather AJM, Holmes A, Ferlie Eet al., 2019, Strengthening strategic management approaches to address antimicrobial resistance in global human health: a scoping review, BMJ Global Health, Vol: 4, ISSN: 2059-7908

Introduction: The development and implementation of national strategic plans is a critical component towards successfully addressing antimicrobial resistance (AMR). This study aimed to review the scope and analytical depth of situation analyses conducted to address AMR in human health to inform the development and implementation of national strategic plans. Methods: A systematic search of the literature was conducted to identify all studies since 2000, that have employed a situation analysis to address AMR. The included studies are analysed against frameworks for strategic analysis, primarily the PESTELI (Political, Economic, Sociological, Technological, Ecological, Legislative, Industry) framework, to understand the depth, scope and utility of current published approaches. Results: 10 studies were included in the final review ranging from single country (6) to regional-level multicountry studies (4). 8 studies carried out documentary review, and 3 of these also included stakeholder interviews. 2 studies were based on expert opinion with no data collection. No study employed the PESTELI framework. Most studies (9) included analysis of the political domain and 1 study included 6 domains of the framework. Technological and industry analyses is a notable gap. Facilitators and inhibitors within the political and legislative domains were the most frequently reported. No facilitators were reported in the economic or industry domains but featured inhibiting factors including: lack of ring-fenced funding for surveillance, perverse financial incentives, cost-shifting to patients; joint-stock drug company ownership complicating regulations. Conclusion: The PESTELI framework provides further opportunities to combat AMR using a systematic, strategic management approach, rather than a retrospective view. Future analysis of existing quantitative data with interviews of key strategic and operational stakeholders is needed to provide critical insights about where implementation eff

Journal article

Peiffer-Smadja N, Rawson TM, Ahmad R, Buchard A, Pantelis G, Lescure F-X, Birgand G, Holmes Aet al., Machine learning for clinical decision support in infectious diseases: A narrative review of current applications, Clinical Microbiology and Infection, ISSN: 1198-743X

BACKGROUNDMachine learning (ML) is a growing field in medicine. This narrative review describes the current body of literature on ML for clinical decision support in infectious diseases (ID). OBJECTIVESWe aim to inform clinicians about the use of ML for diagnosis, classification, outcome prediction and antimicrobial management in ID.SOURCESReferences for this review were identified through searches of MEDLINE/PubMed, EMBASE, Google Scholar, biorXiv, ACM Digital Library, arXiV and IEEE Xplore Digital Library up to July 2019.CONTENTWe found 60 unique ML-CDSS aiming to assist ID clinicians. Overall, 37 (62%) focused on bacterial infections, 10 (17%) on viral infections, nine (15%) on tuberculosis and four (7%) on any kind of infection. Among them, 20 (33%) addressed the diagnosis of infection, 18 (30%) the prediction, early detection or stratification of sepsis, 13 (22%) the prediction of treatment response, four (7%) the prediction of antibiotic resistance, three (5%) the choice of antibiotic regimen and two (3%) the choice of a combination antiretroviral therapy. The ML-CDSS were developed for intensive care units (n=24, 40%), ID consultation (n=15, 25%), medical or surgical wards (n=13, 20%), emergency department (n=4, 7%), primary care (n=3, 5%) and antimicrobial stewardship (n=1, 2%). Fifty-three ML-CDSS (88%) were developed using data from high-income countries and seven (12%) with data from low- and middle-income countries (LMIC). The evaluation of ML-CDSS was limited to measures of performance (e.g. sensitivity, specificity) for 57 ML-CDSS (95%) and included data in clinical practice for three (5%). IMPLICATIONSConsidering comprehensive patient data from socioeconomically diverse health care settings, including primary care and LMICs, may improve the ability of ML-CDSS to suggest decisions adapted to various clinical contexts. Currents gaps identified in the evaluation of ML-CDSS must also be addressed in order to know the potential impact of such tools for cli

Journal article

Balinskaite V, Johnson AP, Holmes A, Aylin Pet al., 2019, The impact of a national antimicrobial stewardship programme on antibiotic prescribing in primary care: an interrupted time series analysis, Clinical Infectious Diseases, Vol: 69, Pages: 227-232, ISSN: 1058-4838

Background: The Quality Premium was introduced in 2015 to financially reward local commissioners of healthcare in England for targeted reductions in antibiotic prescribing in primary care. Methods: We used a national antibiotic prescribing dataset from April 2013 till February 2017 to examine the number of antibiotic items prescribed, the total number of antibiotic items prescribed per STAR-PU (Specific Therapeutic Group Age-sex Related Prescribing Units), the number of broad-spectrum antibiotic items prescribed and broad-spectrum antibiotic items prescribed expressed as a percentage of the total number of antibiotic items. To evaluate the impact of the Quality Premium on antibiotic prescribing, we used a segmented regression analysis of interrupted time series data. Results: During the study period, over 140 million antibiotic items were prescribed in primary care. Following the introduction of the Quality Premium, antibiotic items prescribed decreased by 8.2%, representing 5,933,563 fewer antibiotic items prescribed during the 23 post-intervention months compared with the expected numbers based on the trend in the pre-intervention period. After adjusting for the age and sex distribution in the population, the segmented regression model also showed a significant relative decrease in antibiotic items prescribed per STAR-PU. A similar effect was found for broad-spectrum antibiotics (comprising 10.1% of total antibiotic prescribing), with an 18.9% reduction in prescribing. Conclusions: This study shows that the introduction of financial incentives for local commissioners of healthcare to improve the quality of prescribing was associated with a significant reduction in both total and broad-spectrum antibiotic prescribing in primary care in England.

Journal article

Troughton R, Mariano V, Campbell A, Hettiaratchy S, Holmes A, Birgand Get al., 2019, Understanding determinants of infection control practices in surgery: the role of shared ownership and team hierarchy, Antimicrobial Resistance and Infection Control, Vol: 8, ISSN: 2047-2994

Background. Despite a large literature on surgical site infection (SSI), the determinants ofprevention behaviours in surgery remain poorly studied. Understanding key social andcontextual components of surgical staff behaviour may help to design and implementinfection control (IC) improvement interventions in surgery.Methods. Qualitative semi-structured interviews were conducted with surgeons (n = 8),nurses (n = 5) theatre personnel (n = 3), and other healthcare professionals involved in surgery(n=4) in a 1500-bed acute care London hospital group. Participants were approached throughestablished mailing lists and snowball sampling. Interviews were recorded and transcribedverbatim. Transcripts were coded and analysed thematically using a constant comparativeapproach.Results. IC behaviour of surgical staff was governed by factors at individual, team, and widerhospital level. IC practices were linked to the perceived risk of harm caused by an SSI morethan the development of an SSI alone. Many operating room participants saw SSI preventionas a team responsibility. The sense of ownership over SSI occurence was closely tied to howpreventable staff perceived infections to be, with differences observed between clean andcontaminated surgery. However, senior surgeons claimed personal accountability for ratesdespite feeling SSIs are often not preventable. Hierarchy impacted on behaviour in differentways depending on whether it was within or between professional categories. One particularknowledge gap highlighted was the lack of awareness regarding criteria for SSI diagnosis.Conclusions. To influence IC behaviours in surgery, interventions need to consider the socialteam structure and shared ownership of the clinical outcome in order to increase theawareness in specialties where SSIs are not seen as serious complications.

Journal article

Balinskaite V, Bou-Antoun S, Johnson AP, Holmes A, Aylin Pet al., 2019, An assessment of potential unintended consequences following a national antimicrobial stewardship programme in England: an interrupted time series analysis, Clinical Infectious Diseases, Vol: 69, Pages: 233-242, ISSN: 1058-4838

Background: The 'Quality Premium' (QP) introduced in England in 2015 aimed to financially reward local healthcare commissioners for targeted reductions in primary care antibiotic prescribing. We aimed to evaluate possible unintended clinical outcomes related to this QP. Methods: Using Clinical Practice Research Datalink and Hospital Episode Statistics datasets, we examined general practitioner (GP) consultations (visits) and emergency hospital admissions related to a series of pre-defined conditions of unintended consequences of reduced prescribing. Monthly age and sex-standardised rates were calculated using a direct method of standardisation. We used segmented regression analysis of interrupted time series to evaluate the impact of the QP on seasonally adjusted outcome rates. Results: We identified 27,334 GP consultations and over five million emergency hospital admissions with pre-defined conditions. There was no evidence that the QP was associated with changes in GP consultation and hospital admission rates for the selected conditions combined. However, when each condition was considered separately, a significant increase in hospital admission rates was noted for quinsy, and significant decreases were seen for hospital-acquired pneumonia, scarlet fever, pyelonephritis and complicated urinary tract conditions. A significant decrease in GP consultation rates was estimated for empyema and scarlet fever. No significant changes were observed for other conditions. Conclusions: Findings from this study show that overall there was no significant association between the intervention and unintended clinical consequences, with the exception of a few specific conditions, most of which could be explained through other parallel policy changes or should be interpreted with caution due to small numbers.

Journal article

Charani E, Ahmad R, Rawson T, Castro-Sanchez E, Tarrant C, Holmes Aet al., 2019, The differences in antibiotic decision-making between acute surgical and acute medical teams: An ethnographic study of culture and team dynamics, Clinical Infectious Diseases, Vol: 69, Pages: 12-20, ISSN: 1058-4838

BackgroundCultural and social determinants influence antibiotic decision-making in hospitals. We investigated and compared cultural determinants of antibiotic decision-making in acute medical and surgical specialties.MethodsAn ethnographic observational study of antibiotic decision-making in acute medical and surgical teams at a London teaching hospital was conducted (August 2015–May 2017). Data collection included 500 hours of direct observations, and face-to-face interviews with 23 key informants. A grounded theory approach, aided by Nvivo 11 software, analyzed the emerging themes. An iterative and recursive process of analysis ensured saturation of the themes. The multiple modes of enquiry enabled cross-validation and triangulation of the findings.ResultsIn medicine, accepted norms of the decision-making process are characterized as collectivist (input from pharmacists, infectious disease, and medical microbiology teams), rationalized, and policy-informed, with emphasis on de-escalation of therapy. The gaps in antibiotic decision-making in acute medicine occur chiefly in the transition between the emergency department and inpatient teams, where ownership of the antibiotic prescription is lost. In surgery, team priorities are split between 3 settings: operating room, outpatient clinic, and ward. Senior surgeons are often absent from the ward, leaving junior staff to make complex medical decisions. This results in defensive antibiotic decision-making, leading to prolonged and inappropriate antibiotic use.ConclusionsIn medicine, the legacy of infection diagnosis made in the emergency department determines antibiotic decision-making. In surgery, antibiotic decision-making is perceived as a nonsurgical intervention that can be delegated to junior staff or other specialties. Different, bespoke approaches to optimize antibiotic prescribing are therefore needed to address these specific challenges.

Journal article

Islam MS, Charani E, Holmes AH, 2019, The AWaRe point prevalence study index: simplifying surveillance of antibiotic use in paediatrics, The Lancet Global Health, Vol: 7, Pages: E811-E812, ISSN: 2214-109X

Journal article

Castro-Sánchez E, Sood A, Rawson TM, Firth J, Holmes AH, Castro Sanchez E, Sood A, Rawson T, Firth J, Holmes Aet al., 2019, Forecasting Implementation, Adoption and Evaluation Challenges For an Electronic Game-Based Antimicrobial Stewardship Intervention: Results of a Codesign Workshop with Experts (Preprint), Journal of Medical Internet Research, Vol: 21, ISSN: 1438-8871

Background:Serious games have been proposed to address the lack of engagement and sustainability traditionally affecting interventions aiming to improve optimal antibiotic use among hospital prescribers.Objectives:To forecast gaps in implementation, adoption and evaluation of game-based interventions, and co-design solutions with antimicrobial clinicians and digital and behavioural researchers. Methods: A co-development workshop with clinicians and academics in serious games, antimicrobials and behavioural sciences was organised to open an international summit on serious games for health in London (United Kingdom), in March 2018. The workshop was announced on social media and online platforms. On the day, attendees were asked to work in small groups provided with a laptop/tablet with the latest version of ‘On call: Antibiotics. A workshop leader guided open group discussions around implementation, adoption and evaluation threats and potential solutions. Workshop summary notes were collated by an observer.Results: 29 participants attended the workshop. Anticipated challenges to resolve reflected implementation threats such as an inadequate organisational arrangement to scale and sustain the use of the game, requiring sufficient technical and educational support and a streamlined feedback mechanism that made best use of data arriving from the game; adoption threats, particularly collective perceptions that a game would be a ludic rather than professional tool, and demanding efforts to integrate all available educational solutions so none is seen as inferior; and evaluation threats due to the need to combine game metrics with organisational indicators such as antibiotic use, which may be difficult to enable.Conclusions:As with other technology-based interventions, organisations interested in deploying game-based solutions should carefully plan how to engage and support clinicians in their use, and how best integrate the game and game outputs onto existing workflo

Journal article

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