Imperial College London

ProfessorAlisonHolmes

Faculty of MedicineDepartment of Infectious Disease

Professor of Infectious Diseases
 
 
 
//

Contact

 

+44 (0)20 3313 1283alison.holmes

 
 
//

Location

 

8N16Hammersmith HospitalHammersmith Campus

//

Summary

 

Publications

Publication Type
Year
to

251 results found

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

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

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

Birgand G, Troughton R, Mariano V, Hettiaratchy S, Hopkins S, Otter JA, Holmes Aet al., How do surgeons feel about the “Getting it Right First Time” national audit? Results from a qualitative assessment., Journal of Hospital Infection, 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

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

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, 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

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

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

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

Castro-Sánchez E, Sood A, Rawson TM, Firth J, Holmes AHet 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

Zingg W, Storr J, Park BJ, Ahmad R, Tarrant C, Castro Sanchez E, Tomczyk S, Kilpatrick C, Allegranzi B, Cardo D, Pittet D, the 2017 Geneva IPC-Think Tanket al., 2019, Implementation research for the prevention of antimicrobial resistance and healthcare-associated infections; 2017 Geneva Infection Prevention and Control (IPC)-Think Tank (Part 1), Antimicrobial Resistance and Infection Control, Vol: 8, ISSN: 2047-2994

BackgroundAround 5–15% of all hospital patients worldwide suffer from healthcare-associated infections (HAIs), and years of excessive antimicrobial use in human and animal medicine have created emerging antimicrobial resistance (AMR). A considerable amount of evidence-based measures have been published to address these challenges, but the largest challenge seems to be their implementation.MethodsIn June 2017, a total of 42 experts convened at the Geneva IPC-Think Tank to discuss four domains in implementation science: 1) teaching implementation skills; 2) fostering implementation of IPC and antimicrobial stewardship (AMS) by policy making; 3) national/international actions to foster implementation skills; and 4) translational research bridging social sciences and clinical research in infection prevention and control (IPC) and AMR.ResultsAlthough neglected in the past, implementation skills have become a priority in IPC and AMS. They should now be part of any curriculum in health care, and IPC career paths should be created. Guidelines and policies should be aligned with each other and evidence-based, each document providing a section on implementing elements of IPC and AMS in patient care. International organisations should be advocates for IPC and AMS, framing them as patient safety issues and emphasizing the importance of implementation skills. Healthcare authorities at the national level should adopt a similar approach and provide legal frameworks, guidelines, and resources to allow better implementation of patient safety measures in IPC and AMS. Rather than repeating effectiveness studies in every setting, we should invest in methods to improve the implementation of evidence-based measures in different healthcare contexts. For this, we need to encourage and financially support collaborations between social sciences and clinical IPC research.ConclusionsExperts of the 2017 Geneva Think Tank on IPC and AMS, CDC, and WHO agreed that sustained efforts on implem

Journal article

Zingg W, Park BJ, Storr J, Ahmad R, Tarrant C, Castro Sanchez E, Perencevich E, Widmer A, Krause K-H, Kilpatrick C, Tomczyk S, Allegranzi B, Cardo D, Pittet Det al., 2019, Technology for the prevention of antimicrobial resistance and healthcare-associated infections; 2017 Geneva IPC-Think Tank (Part 2), Antimicrobial Resistance and Infection Control, Vol: 8, ISSN: 2047-2994

BackgroundThe high burden of healthcare-associated infections (HAIs) and antimicrobial resistance (AMR) is partially due to excessive antimicrobial use both in human and animal medicine worldwide. How can technology help to overcome challenges in infection prevention and control (IPC) and to prevent HAI and emerging AMR?MethodsIn June 2017, 42 international experts convened in Geneva, Switzerland to discuss four potential domains of technology in IPC and AMR: 1) role and potential contribution of microbiome research; 2) whole genome sequencing; 3) effectiveness and benefit of antimicrobial environmental surfaces; and 4) future research in hand hygiene.ResultsResearch on the microbiome could expand understanding of antimicrobial use and also the role of probiotics or even faecal transplantation for therapeutic purposes. Whole genome sequencing will provide new insights in modes of transmission of infectious diseases. Although it is a powerful tool for public health epidemiology, some challenges with interpretation and costs still need to be addressed. The effectiveness and cost-effectiveness of antimicrobially coated or treated environmental high-touch surfaces requires further research before they can be recommended for routine use. Hand hygiene implementation can be advanced, where technological enhancement of surveillance, technique and compliance are coupled with reminders for healthcare professionals.ConclusionsThe four domains of technological innovation contribute to the prevention of HAI and AMR at different levels. Microbiome research may offer innovative concepts for future prevention, whole genome sequencing could detect new modes of transmission and become an additional tool for effective public health epidemiology, antimicrobial surfaces might help to decrease the environment as source of transmission but continue to raise more questions than answers, and technological innovation may have a role in improving surveillance approaches and supporting best pr

Journal article

Zingg W, Storr J, Park BJ, Jernigan JA, Harbarth S, Grayson ML, Tacconelli E, Allegranzi B, Cardo D, Pittet D, Abbas M, Ahmad R, Ailegranzi B, Andremont A, Bell M, Borg M, Carmeli Y, Castro-Sanchez E, Conly J, Eggimann P, Gastmeier P, Hernandez M, Hetwaldt L, Holmes A, Kilpatrick C, Kolwaite A, Krause K-H, Larson E, Masson-Roy S, Mehtar S, Mendelson M, Lin LM, Moldovan A, Monnet D, Ndoye B, Nthumba P, Ogunsola F, Park B, Perencevich E, Samore M, Seto WH, Srinivasan A, Tarrant C, Tomczyk S, Talaat M, Villegas MV, Voss A, Walsh T, Widmer Aet al., 2019, Broadening the infection prevention and control network globally; 2017 Geneva IPC-think tank (part 3), Antimicrobial Resistance and Infection Control, Vol: 8, Pages: 1-5, ISSN: 2047-2994

BackgroundHealthcare-associated infection (HAI) is a major challenge for patient safety worldwide, and is further complicated by antimicrobial resistance (AMR) due to excessive antimicrobial use in both humans and animals. Existing infection prevention and control (IPC) networks must be strengthened and adapted to better address the global challenges presented by emerging AMR.MethodsIn June 2017, 42 international experts convened in Geneva, Switzerland, to discuss two key areas for strengthening the global IPC network: 1) broadening collaboration in IPC; and 2) how to bring the fields IPC and AMR control together.ResultsThe US Centers for Disease Prevention and Control, the European Centre for Disease Prevention and Control, and the World Health Organization (WHO) convened together with international experts to discuss collaboration and networks, demonstrating the participating organizations’ commitment to close collaboration in IPC. The challenge of emerging AMR can only be addressed by strengthening this collaboration across international organisations and between public health and academia. The WHO SAVE LIVES: Clean Your Hands initiative is an example of a successful collaboration between multiple global stakeholders including academia and international public health organisations; it can be used as a model. IPC-strategies are included within the four pillars to combat AMR: surveillance, IPC, antimicrobial and diagnostic stewardship, research and development. The prevention of transmission of multidrug-resistant microorganisms is a patient safety issue, and must be strengthened in the fight against AMR.ConclusionsThe working group determined that international organisations should take the lead in creating new networks, which will in turn attract academia and other stakeholders to join. At the same time, they should invest in bringing existing IPC and AMR networks under one umbrella. Transmission of multidrug-resistant microorganisms in hospitals and in the

Journal article

Moniri A, Rodriguez-Manzano J, Malpartida-Cardenas K, Yu L-S, Didelot X, Holmes A, Georgiou Pet al., 2019, Framework for DNA quantification and outlier detection using multidimensional standard curves, Analytical Chemistry, Vol: 91, Pages: 7426-7434, ISSN: 0003-2700

Real-time PCR is a highly sensitive and powerful technology for the quantification of DNA and has become the method of choice in microbiology, bioengineering, and molecular biology. Currently, the analysis of real-time PCR data is hampered by only considering a single feature of the amplification profile to generate a standard curve. The current “gold standard” is the cycle-threshold (Ct) method which is known to provide poor quantification under inconsistent reaction efficiencies. Multiple single-feature methods have been developed to overcome the limitations of the Ct method; however, there is an unexplored area of combining multiple features in order to benefit from their joint information. Here, we propose a novel framework that combines existing standard curve methods into a multidimensional standard curve. This is achieved by considering multiple features together such that each amplification curve is viewed as a point in a multidimensional space. Contrary to only considering a single-feature, in the multidimensional space, data points do not fall exactly on the standard curve, which enables a similarity measure between amplification curves based on distances between data points. We show that this framework expands the capabilities of standard curves in order to optimize quantification performance, provide a measure of how suitable an amplification curve is for a standard, and thus automatically detect outliers and increase the reliability of quantification. Our aim is to provide an affordable solution to enhance existing diagnostic settings through maximizing the amount of information extracted from conventional instruments.

Journal article

Ming DK, Otter JA, Ghani R, Brannigan ET, Boonyasiri A, Mookerjee S, Gilchrist M, Holmes AH, Davies Fet al., 2019, Clinical risk stratification and antibiotic management of NDM and OXA-48 carbapenemase-producing Enterobacteriaceae bloodstream infections in the UK, Journal of Hospital Infection, Vol: 102, Pages: 95-97, ISSN: 0195-6701

Journal article

Desai AN, Ramatowski JW, Lassmann B, Holmes A, Mehtar S, Bearman Get al., 2019, Global infection prevention gaps, needs, and utilization of educational resources: A cross-sectional assessment by the International Society for Infectious Diseases, International Journal of Infectious Diseases, Vol: 82, Pages: 54-60, ISSN: 1201-9712

OBJECTIVE: The Guide to Infection Control in the Hospital (Guide) is an open access resource produced by the International Society for Infectious Diseases (ISID) to assist in the prevention of infection acquisition and transmission worldwide. A survey was distributed to 8055 current Guide users to understand their needs. METHODS: The survey consisted of 48-questions regarding infection prevention and control (IPC) availability and needs. Dichotomous questions, Likert scale-type questions, and open-and closed-ended questions were used. RESULTS: Respondents (n=1121) from 194 countries and six WHO regions participated in the survey. 43% (488) identified as physicians. Personal protective equipment (PPE) availability, training, and antimicrobial susceptibility testing varied between regions. Only 11% of respondents from low-income countries reported consistent access to respiratory equipment, 12% to isolation gowns, 4% to negative pressure rooms or personnel trained in IPC, and 20% to antimicrobial resistance testing. This differed significantly to high and upper middle-income resource settings (p<0.05). 80% of all respondents used smartphones or tablets at the workplace. CONCLUSIONS: This survey demonstrates varied access to IPC equipment and training between high and low-income settings worldwide. Our results demonstrated many respondents across all regions utilize mobile technology, providing opportunities for rapid distribution of resource specific, up-to-date IPC content.

Journal article

Gowers SAN, Freeman DME, Rawson TM, Rogers ML, Wilson RC, Holmes AH, Cass AE, O'Hare Det al., 2019, Development of a minimally invasive microneedle-based sensor for continuous monitoring of β-lactam antibiotic concentrations in vivo, ACS Sensors, Vol: 4, Pages: 1072-1080, ISSN: 2379-3694

Antimicrobial resistance poses a global threat to patient health. Improving the use and effectiveness of antimicrobials is critical in addressing this issue. This includes optimizing the dose of antibiotic delivered to each individual. New sensing approaches that track antimicrobial concentration for each patient in real time could allow individualized drug dosing. This work presents a potentiometric microneedle-based biosensor to detect levels of β-lactam antibiotics in vivo in a healthy human volunteer. The biosensor is coated with a pH-sensitive iridium oxide layer, which detects changes in local pH as a result of β-lactam hydrolysis by β-lactamase immobilized on the electrode surface. Development and optimization of the biosensor coatings are presented, giving a limit of detection of 6.8 μM in 10 mM PBS solution. Biosensors were found to be stable for up to 2 weeks at -20 °C and to withstand sterilization. Sensitivity was retained after application for 6 h in vivo. Proof-of-concept results are presented showing that penicillin concentrations measured using the microneedle-based biosensor track those measured using both discrete blood and microdialysis sampling in vivo. These preliminary results show the potential of this microneedle-based biosensor to provide a minimally invasive means to measure real-time β-lactam concentrations in vivo, representing an important first step toward a closed-loop therapeutic drug monitoring system.

Journal article

Kyratsis Y, Ahmad R, Iwami M, Castro-Sánchez E, Atun R, Holmes AHet al., 2019, A multilevel neo-institutional analysis of infection prevention and control in English hospitals: coerced safety culture change?, Sociol Health Illn

Despite committed policy, regulative and professional efforts on healthcare safety, little is known about how such macro-interventions permeate organisations and shape culture over time. Informed by neo-institutional theory, we examined how inter-organisational influences shaped safety practices and inter-subjective meanings following efforts for coerced culture change. We traced macro-influences from 2000 to 2015 in infection prevention and control (IPC). Safety perceptions and meanings were inductively analysed from 130 in-depth qualitative interviews with senior- and middle-level managers from 30 English hospitals. A total of 869 institutional interventions were identified; 69% had a regulative component. In this context of forced implementation of safety practices, staff experienced inherent tensions concerning the scope of safety, their ability to be open and prioritisation of external mandates over local need. These tensions stemmed from conflicts among three co-existing institutional logics prevalent in the NHS. In response to requests for change, staff flexibly drew from a repertoire of cognitive, material and symbolic resources within and outside their organisations. They crafted 'strategies of action', guided by a situated assessment of first-hand practice experiences complementing collective evaluations of interventions such as 'pragmatic', 'sensible' and also 'legitimate'. Macro-institutional forces exerted influence either directly on individuals or indirectly by enriching the organisational cultural repertoire.

Journal article

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

Request URL: http://wlsprd.imperial.ac.uk:80/respub/WEB-INF/jsp/search-html.jsp Request URI: /respub/WEB-INF/jsp/search-html.jsp Query String: respub-action=search.html&id=00171222&limit=30&person=true