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
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277 results found

Rawson TM, Wilson R, Holmes A, 2020, Understanding the role of bacterial and fungal infection in COVID-19, Clinical Microbiology and Infection, ISSN: 1198-743X

Journal article

Moniri A, Miglietta L, Malpartida Cardenas K, Pennisi I, Cacho Soblechero M, Moser N, Holmes A, Georgiou P, Rodriguez Manzano Jet al., 2020, Amplification curve analysis: Data-driven multiplexing using real-time digital PCR, Analytical Chemistry, ISSN: 0003-2700

Information about the kinetics of PCR reactions are encoded in the amplification curve. However, in digital PCR (dPCR), this information is typically neglected by collapsing each amplification curve into a binary output (positive/negative). Here, we demonstrate that the large volume of raw data obtained from realtime dPCR instruments can be exploited to perform data-driven multiplexing in a single fluorescent channel using machine learning methods, by virtue of the information in the amplification curve. This new approach, referred to as amplification curve analysis (ACA), was shown using an intercalating dye (EvaGreen), reducing the cost and complexity of the assay and enabling the use of melting curve analysis for validation. As a case study, we multiplexed 3 carbapenem-resistant genes to show the impact of this approach on global challenges such as antimicrobial resistance. In the presence of single targets, we report a classification accuracy of 99.1% (N = 16188) which represents a 19.7% increase compared to multiplexing based on the final fluorescent intensity. Considering all combinations of amplification events (including coamplifications), the accuracy was shown to be 92.9% (N = 10383). To support the analysis, we derived a formula to estimate the occurrence of co-amplification in dPCR based on multivariate Poisson statistics, and suggest reducing the digital occupancy in the case of multiple targets in the same digital panel. The ACA approach takes a step towards maximizing the capabilities of existing real-time dPCR instruments and chemistries, by extracting more information from data to enable data-driven multiplexing with high accuracy. Furthermore, we expect that combining this method with existing probe-based assays will increase multiplexing capabilities significantly. We envision that once emerging point-of-care technologies can reliably capture real-time data from isothermal chemistries, the ACA method will facilitate the implementation of dPCR outs

Journal article

Yu L-S, Rodriguez-Manzano J, Moser N, Moniri A, Malpartida-Cardenas K, Miscourides N, Sewell T, Kochina T, Brackin A, Rhodes J, Holmes AH, Fisher MC, Georgiou Pet al., 2020, Rapid detection of azole-resistant Aspergillus fumigatus in clinical and environmental isolates using lab-on-a-chip diagnostic system, Journal of Clinical Microbiology, ISSN: 0095-1137

Aspergillus fumigatus has widely evolved resistance to the most commonly used class of antifungal chemicals, the azoles. Current methods for identifying azole resistance are time-consuming and depend on specialized laboratories. There is an urgent need for rapid detection of these emerging pathogens at point-of-care to provide the appropriate treatment in the clinic and to improve management of environmental reservoirs to mitigate the spread of antifungal resistance. Our study demonstrates the rapid and portable detection of the two most relevant genetic markers linked to azole resistance, the mutations TR34 and TR46, found in the promoter region of the gene encoding the azole target, cyp51A. We developed a lab-on-a-chip platform consisting of: (1) tandem-repeat loop-mediated isothermal amplification, (2) state-of-the-art complementary metal-oxide-semiconductor microchip technology for nucleic-acid amplification detection and, (3) and a smartphone application for data acquisition, visualization and cloud connectivity. Specific and sensitive detection was validated with isolates from clinical and environmental samples from 6 countries across 5 continents, showing a lower limit-of-detection of 10 genomic copies per reaction in less than 30 minutes. When fully integrated with a sample preparation module, this diagnostic system will enable the detection of this ubiquitous fungus at the point-of-care, and could help to improve clinical decision making, infection control and epidemiological surveillance.

Journal article

Peiffer-Smadja N, Allison R, Jones LF, Holmes A, Patel P, Lecky DM, Ahmad R, McNulty CAMet al., 2020, Preventing and Managing Urinary Tract Infections: Enhancing the Role of Community Pharmacists-A Mixed Methods Study., Antibiotics (Basel), Vol: 9, ISSN: 2079-6382

BACKGROUND: Community pharmacists are involved in antimicrobial stewardship through self-care advice and delivering medications for uncomplicated infections. OBJECTIVES: This mixed methods study aimed to identify opportunities to enhance the role of community pharmacists in the management of service users with suspected or confirmed urinary tract infection (UTI). METHODS: Data collection was through a service user survey (n = 51) and pharmacist surveys and semi-structured interviews before (16 interviews, 22 questionnaires) and after (15 interviews, 16 questionnaires) trialing UTI leaflets designed to be shared with service users. Data were analysed inductively using thematic analysis and descriptive tabulation of quantitative data. RESULTS: Twenty-five percent (n = 13/51) of service users with urinary symptoms sought help from a pharmacist first and 65% (n = 33/51) were comfortable discussing their urinary symptoms with a pharmacist in a private space. Community pharmacists were confident as the first professional contact for service users with uncomplicated UTI (n = 13/16, 81%), but indicated the lack of a specific patient referral pathway (n = 16/16, 100%), the need for additional funding and staff (n = 10/16, 62%), and the importance of developing prescription options for pharmacists (5/16, 31%). All community pharmacists reported playing a daily role in controlling antimicrobial resistance by educating service users about viral and bacterial infections and promoting a healthy lifestyle. Enhancing their role will need greater integrated working with general practices and more prescribers based in community pharmacy. CONCLUSION: This study suggests that community pharmacists could play a greater role in the management of uncomplicated UTI. The current reconfiguration of primary care in England with primary care networks and integrated care systems could provide a real opportunity for this collaborative working with potential learning for international initiatives

Journal article

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, Vol: 75, Pages: 2670-2676

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

Borek AJ, Anthierens S, Allison R, McNulty CAM, Lecky DM, Costelloe C, Holmes A, Butler CC, Walker AS, Tonkin-Crine Set al., 2020, How did a Quality Premium financial incentive influence antibiotic prescribing in primary care? Views of Clinical Commissioning Group and general practice professionals., J Antimicrob Chemother, Vol: 75, Pages: 2681-2688

BACKGROUND: The Quality Premium (QP) was introduced for Clinical Commissioning Groups (CCGs) in England to optimize antibiotic prescribing, but it remains unclear how it was implemented. OBJECTIVES: To understand responses to the QP and how it was perceived to influence antibiotic prescribing. METHODS: Semi-structured telephone interviews were conducted with 22 CCG and 19 general practice professionals. Interviews were analysed thematically. RESULTS: The findings were organized into four categories. (i) Communication: this was perceived as unstructured and infrequent, and CCG professionals were unsure whether they received QP funding. (ii) Implementation: this was influenced by available local resources and competing priorities, with multifaceted and tailored strategies seen as most helpful for engaging general practices. Many antimicrobial stewardship (AMS) strategies were implemented independently from the QP, motivated by quality improvement. (iii) Mechanisms: the QP raised the priority of AMS nationally and locally, and provided prescribing targets to aim for and benchmark against, but money was not seen as reinvested into AMS. (iv) Impact and sustainability: the QP was perceived as successful, but targets were considered challenging for a minority of CCGs and practices due to contextual factors (e.g. deprivation, understaffing). CCG professionals were concerned with potential discontinuation of the QP and prescribing rates levelling off. CONCLUSIONS: CCG and practice professionals expressed positive views of the QP and associated prescribing targets and feedback. The QP helped influence change mainly by raising the priority of AMS and defining change targets rather than providing additional funding. To maximize impact, behavioural mechanisms of financial incentives should be considered pre-implementation.

Journal article

Boyd SE, Vasudevan A, Moore LSP, Brewer C, Gilchrist M, Costelloe C, Gordon AC, Holmes AHet al., 2020, Validating a prediction tool to determine the risk of nosocomial multidrug-resistant Gram-negative bacilli infection in critically ill patients: A retrospective case-control study., J Glob Antimicrob Resist, Vol: 22, Pages: 826-831

BACKGROUND: The Singapore GSDCS score was developed to enable clinicians predict the risk of nosocomial multidrug-resistant Gram-negative bacilli (RGNB) infection in critically ill patients. We aimed to validate this score in a UK setting. METHOD: A retrospective case-control study was conducted including patients who stayed for more than 24h in intensive care units (ICUs) across two tertiary National Health Service hospitals in London, UK (April 2011-April 2016). Cases with RGNB and controls with sensitive Gram-negative bacilli (SGNB) infection were identified. RESULTS: The derived GSDCS score was calculated from when there was a step change in antimicrobial therapy in response to clinical suspicion of infection as follows: prior Gram-negative organism, Surgery, Dialysis with end-stage renal disease, prior Carbapenem use and intensive care Stay of more than 5 days. A total of 110 patients with RGNB infection (cases) were matched 1:1 to 110 geotemporally chosen patients with SGNB infection (controls). The discriminatory ability of the prediction tool by receiver operating characteristic curve analysis in our validation cohort was 0.75 (95% confidence interval 0.65-0.81), which is comparable with the area under the curve of the derivation cohort (0.77). The GSDCS score differentiated between low- (0-1.3), medium- (1.4-2.3) and high-risk (2.4-4.3) patients for RGNB infection (P<0.001) in a UK setting. CONCLUSION: A simple bedside clinical prediction tool may be used to identify and differentiate patients at low, medium and high risk of RGNB infection prior to initiation of prompt empirical antimicrobial therapy in the intensive care setting.

Journal article

Charani E, Singh S, Mendelson M, Veepanattu P, Nampoothiri V, Edathadatil F, Surendran S, Bonaconsa C, Mbamalu O, Ahuja S, Sevdalis N, Tarrant C, Birgand G, Castro-SAnchez E, Ahmad R, Holmes Aet al., 2020, Building resilient and responsive research collaborations to tackle antimicrobial resistance – lessons learnt from India, South Africa and UK, International Journal of Infectious Diseases, ISSN: 1201-9712

Research, collaboration and knowledge exchange are critical to global efforts to tackle antimicrobial resistance (AMR). Different healthcare economies are faced with different challenges in implementing effective strategies to address AMR. Building effective capacity for research to inform AMR related strategies and policies AMR is recognised as an important contributor to success. Interdisciplinary, inter-sector, as well as inter-country collaboration is needed to span AMR efforts from the global to local. Developing reciprocal, long-term, partnerships between collaborators in high-income and low- and middle-income countries (LMICs) needs to be built on principles of capacity building. Using case-studies spanning local to international research collaborations to co-design, implement and evaluate strategies to tackle AMR, we evaluate and build upon the ESSENCE criteria for capacity building in LMICs. The first case-study describes the local co-design and implementation of antimicrobial stewardship in the state of Kerala in India. The second case-study describes an international research collaboration investigating AMR across surgical pathways in India, UK and South Africa. We describe the steps undertaken to develop robust, agile, and flexible antimicrobial stewardship research and implementation teams. Notably, investing in capacity building ensured that the programmes described in these case-studies were sustained through the current severe acute respiratory syndrome corona virus pandemic. Describing the strategies adopted by a local and an international collaboration to tackle AMR, we provide a model for capacity building in LMICs that can support sustainable and agile antimicrobial stewardship programmes.

Journal article

Zhu J, Ahmad R, Holmes A, Robotham J, Lebcir R, Atun Ret al., 2020, System dynamics modelling to formulate policy interventions to optimise antibiotic prescribing in hospitals, Journal of the Operational Research Society, ISSN: 0160-5682

Multiple strategies have been used in the National Health System (NHS) in England to reduce inappropriate antibiotic prescribing and consumption in order to tackle antimicrobial resistance. These strategies have included, among others, restricting dispensing, introduction of prescribing guidelines, use of clinical audit, and performance reviews as well as strategies aimed at changing the prescribing behaviour of clinicians. However, behavioural interventions have had limited effect in optimising doctors’ antibiotic prescribing practices. This study examines the determinants of decision-making for antibiotic prescribing in hospitals in the NHS. A system dynamics model was constructed to capture structural and behavioural influences to simulate doctors’ prescribing practices. Data from the literature, patient records, healthcare professional interviews and survey responses were used to parameterise the model. The scenario simulation shows maximum improvements in guideline compliance are achieved when compliance among senior staff is increased, combined with fast laboratory turnaround of blood cultures, and microbiologist review. Improving guideline compliance of junior staff alone has limited impact. This first use of system dynamics modelling to study antibiotic prescribing decision-making demonstrates the applicability of the methodology for design and evaluation of future policies and interventions.

Journal article

Conly J, Seto WH, Pittet D, Holmes A, Chu M, Hunter PRet al., 2020, Use of medical face masks versus particulate respirators as a component of personal protective equipment for health care workers in the context of the COVID-19 pandemic, ANTIMICROBIAL RESISTANCE AND INFECTION CONTROL, Vol: 9, ISSN: 2047-2994

Journal article

Peiffer-Smadja N, Rawson TM, Ahmad R, Buchard A, Georgiou P, Lescure F-X, Birgand G, Holmes AHet al., 2020, machine learning for clinical decision support in infectious diseases: a narrative review of current applications (vol 26, pg 584, 2020), CLINICAL MICROBIOLOGY AND INFECTION, Vol: 26, Pages: 1118-1118, ISSN: 1198-743X

Journal article

Abbas M, Holmes A, Price J, 2020, Surgical site infections following elective surgery, LANCET INFECTIOUS DISEASES, Vol: 20, Pages: 898-899, ISSN: 1473-3099

Journal article

Zhou J, Otter JA, Price JR, Cimpeanu C, Garcia DM, Kinross J, Boshier PR, Mason S, Bolt F, Holmes AH, Barclay WSet al., 2020, Investigating SARS-CoV-2 surface and air contamination in an acute healthcare setting during the peak of the COVID-19 pandemic in London., Clinical Infectious Diseases, ISSN: 1058-4838

BACKGROUND: Evaluation of SARS-CoV-2 surface and air contamination during the COVID-19 pandemic in London. METHODS: We performed this prospective cross-sectional observational study in a multi-site London hospital. Air and surface samples were collected from seven clinical areas, occupied by patients with COVID-19, and a public area of the hospital. Three or four 1.0 m3 air samples were collected in each area using an active air sampler. Surface samples were collected by swabbing items in the immediate vicinity of each air sample. SARS-CoV-2 was detected by RT-qPCR and viral culture; the limit of detection for culturing SARS-CoV-2 from surfaces was determined. RESULTS: Viral RNA was detected on 114/218 (52.3%) of surfaces and 14/31 (38.7%) air samples but no virus was cultured. The proportion of surface samples contaminated with viral RNA varied by item sampled and by clinical area. Viral RNA was detected on surfaces and in air in public areas of the hospital but was more likely to be found in areas immediately occupied by COVID-19 patients than in other areas (67/105 (63.8%) vs. 29/64 (45.3%) (odds ratio 0.5, 95% confidence interval 0.2-0.9, p=0.025, Chi squared test)). The high PCR Ct value for all samples (>30) indicated that the virus would not be culturable. CONCLUSIONS: Our findings of extensive viral RNA contamination of surfaces and air across a range of acute healthcare settings in the absence of cultured virus underlines the potential risk from environmental contamination in managing COVID-19, and the need for effective use of PPE, physical distancing, and hand/surface hygiene.

Journal article

Price JR, Mookerjee S, Dyakova E, Myall A, Leung W, Weiße AY, Shersing Y, Brannigan ET, Galletly T, Muir D, Randell P, Davies F, Bolt F, Barahona M, Otter JA, Holmes AHet al., 2020, Development and delivery of a real-time hospital-onset COVID-19 surveillance system using network analysis, Clinical Infectious Diseases, ISSN: 1058-4838

BackgroundUnderstanding nosocomial acquisition, outbreaks and transmission chains in real-time will be fundamental to ensuring infection prevention measures are effective in controlling COVID-19 in healthcare. We report the design and implementation of a hospital-onset COVID-19 infection (HOCI) surveillance system for an acute healthcare setting to target prevention interventions.MethodsThe study took place in a large teaching hospital group in London, UK. All patients tested for SARS-CoV-2 between 4th March and 14th April 2020 were included. Utilising data routinely collected through electronic healthcare systems we developed a novel surveillance system for determining and reporting HOCI incidence and providing real-time network analysis. We provided daily reports on incidence and trends over time to support HOCI investigation, and generated geo-temporal reports using network analysis to interrogate admission pathways for common epidemiological links to infer transmission chains. By working with stakeholders the reports were co-designed for end users.ResultsReal-time surveillance reports revealed: changing rates of HOCI throughout the course of the COVID-19 epidemic; key wards fuelling probable transmission events; HOCIs over-represented in particular specialities managing high-risk patients; the importance of integrating analysis of individual prior pathways; and the value of co-design in producing data visualisation. Our surveillance system can effectively support national surveillance.ConclusionsThrough early analysis of the novel surveillance system we have provided a description of HOCI rates and trends over time using real-time shifting denominator data. We demonstrate the importance of including the analysis of patient pathways and networks in characterising risk of transmission and targeting infection control interventions.

Journal article

Pollack M, Madoff LC, Tambyah PA, Mendelson M, Holmes Aet al., 2020, International Society for Infectious Diseases - Sustained and continuous funding for WHO, INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, Vol: 96, Pages: 458-458, ISSN: 1201-9712

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 SCet al., 2020, Finding the relevance of antimicrobial stewardship for cystic fibrosis, JOURNAL OF CYSTIC FIBROSIS, Vol: 19, Pages: 511-520, ISSN: 1569-1993

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, INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, Vol: 96, Pages: 233-239, ISSN: 1201-9712

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, Vol: 96, Pages: 648-654, 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

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, Vol: 75, Pages: 1681-1684, 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 LSP, Zhu N, Ranganathan N, Skolimowska K, Gilchrist M, Satta G, Cooke G, Holmes Aet al., 2020, Response to Dudoignon et al., Clin Infect Dis

Journal article

Rawson TM, Ming D, Ahmad R, Moore LSP, Holmes AHet al., 2020, Antimicrobial use, drug-resistant infections and COVID-19., Nature Reviews Microbiology, ISSN: 1740-1526

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, 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

Peiffer-Smadja N, Rawson TM, Ahmad R, Buchard A, Pantelis G, Lescure F-X, Birgand G, Holmes Aet al., 2020, Machine learning for clinical decision support in infectious diseases: A narrative review of current applications, Clinical Microbiology and Infection, Vol: 26, Pages: 584-595, 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

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

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

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