Imperial College London

ProfessorAlisonHolmes

Faculty of MedicineDepartment of Infectious Disease

Professor of Infectious Diseases
 
 
 
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Contact

 

+44 (0)20 3313 1283alison.holmes

 
 
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Location

 

8N16Hammersmith HospitalHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

440 results found

Naylor N, Yamashita K, Iwami M, Kunisawa S, Mizuno S, Castro-Sánchez E, Imanaka Y, Ahmad R, Holmes Aet al., 2020, Code-sharing in cost-of-illness calculations: an application to antibiotic-resistant bloodstream infections, Frontiers in Public Health, Vol: 8, ISSN: 2296-2565

Background: More data-driven evidence is needed on the cost of antibiotic resistance. Both Japan and England have large surveillance and administrative datasets. Code sharing of costing models enables reduced duplication of effort in research.Objective: To estimate the burden of antibiotic-resistant Staphylococcus aureus bloodstream infections (BSIs) in Japan, utilizing code that was written to estimate the hospital burden of antibiotic-resistant Escherichia coli BSIs in England. Additionally, the process in which the code-sharing and application was performed is detailed, to aid future such use of code-sharing in health economics.Methods: National administrative data sources were linked with voluntary surveillance data within the Japan case study. R software code, which created multistate models to estimate the excess length of stay associated with different exposures of interest, was adapted from previous use and run on this dataset. Unit costs were applied to estimate healthcare system burden in 2017 international dollars (I$).Results: Clear supporting documentation alongside open-access code, licensing, and formal communication channels, helped the re-application of costing code from the English setting within the Japanese setting. From the Japanese healthcare system perspective, it was estimated that there was an excess cost of I$6,392 per S. aureus BSI, whilst oxacillin resistance was associated with an additional I$8,155.Conclusions: S. aureus resistance profiles other than methicillin may substantially impact hospital costs. The sharing of costing models within the field of antibiotic resistance is a feasible way to increase burden evidence efficiently, allowing for decision makers (with appropriate data available) to gain rapid cost-of-illness estimates.

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., 2020, A multi-species cluster of GES-5 carbapenemase producing Enterobacterales linked by a geographically disseminated plasmid, Clinical Infectious Diseases, Vol: 71, Pages: 2553-2560, ISSN: 1058-4838

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

Pouwels KB, Vansteelandt S, Batra R, Edgeworth J, Wordsworth S, Robotham JV, Improving the uptake and SusTainability of Effective interventions to promote Prudent antibiotic Use and Primary care STEP-UP Teamet al., 2020, Estimating the effect of healthcare-associated infections on excess length of hospital stay using inverse probability-weighted survival curves, Clinical Infectious Diseases, Vol: 71, Pages: e415-e420, ISSN: 1058-4838

BACKGROUND: Studies estimating excess length of stay (LOS) attributable to nosocomial infections have failed to address time-varying confounding, likely leading to overestimation of their impact. We present a methodology based on inverse probability-weighted survival curves to address this limitation. METHODS: A case study focusing on intensive care unit-acquired bacteremia using data from 2 general intensive care units (ICUs) from 2 London teaching hospitals were used to illustrate the methodology. The area under the curve of a conventional Kaplan-Meier curve applied to the observed data was compared with that of an inverse probability-weighted Kaplan-Meier curve applied after treating bacteremia as censoring events. Weights were based on the daily probability of acquiring bacteremia. The difference between the observed average LOS and the average LOS that would be observed if all bacteremia cases could be prevented was multiplied by the number of admitted patients to obtain the total excess LOS. RESULTS: The estimated total number of extra ICU days caused by 666 bacteremia cases was estimated at 2453 (95% confidence interval [CI], 1803-3103) days. The excess number of days was overestimated when ignoring time-varying confounding (2845 [95% CI, 2276-3415]) or when completely ignoring confounding (2838 [95% CI, 2101-3575]). CONCLUSIONS: ICU-acquired bacteremia was associated with a substantial excess LOS. Wider adoption of inverse probability-weighted survival curves or alternative techniques that address time-varying confounding could lead to better informed decision making around nosocomial infections and other time-dependent exposures.

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, Vol: 58, Pages: 1-11, 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

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, Vol: 100, Pages: 278-282, 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

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

Singh S, Mendelson M, Surendran S, Bonaconsa C, Mbamalu O, Nampoothiri V, Boutall A, Hampton M, Dhar P, Pennel T, Tarrant C, Leather A, Holmes A, Charani Eet al., 2020, Towards a framework approach to integrating pathways for infection prevention and antibiotic stewardship in surgery: a qualitative study from India and South Africa

<jats:title>Abstract</jats:title> <jats:p>BackgroundThe surgical pathway remains a hard to reach, critical target for antimicrobial stewardship (AMS) and infection prevention and control (IPC). We investigated the drivers for surgical AMS and IPC, across cardiovascular and thoracic surgery (CVTS) and gastrointestinal surgery teams in two academic hospitals in South Africa (SA) and India.Materials and methodsAn ethnographic observational study of IPC and AMS was conducted (July 2018–August 2019), with data gathered from 190 hours of non-participant observations (138 India, 60 SA); face-to-face interviews with patients (6 India, 7 South Africa), and healthcare professionals (HCPs) (44 India, 61 SA); and, in-depth patient case studies (4 India, 2 SA). A grounded theory approach aided by Nvivo 11 software, analyzed the emerging themes. An iterative and recursive process of moving between the coded data and the higher-level themes, ensured saturation of the themes. The multiple modes of enquiry enabled cross-validation and triangulation of findings.ResultsAcross surgical pathways, multiple barriers exist impeding effective IPC and AMS practices. The existing, implicit roles of HCPs (including nurses, and senior surgeons) are overlooked as interventions target junior doctors, bypassing the opportunity for integrating care across the surgical team members. Critically, the ownership of decisions remains with the operating surgeons and entrenched hierarchies restrict the integration of other HCPs in IPC and AMS.ConclusionsIPC and AMS are not integrated in surgery. Identifying the implicit existing HCPs roles in IPC and AMS is critical and will facilitate the development of effective and transparent processes across the surgical team for IPC and AMS. Developing a framework approach that includes nurse leadership, empowering pharmacists and engaging surgical leads is essential for integrated care.</jats:p>

Journal article

Moniri A, Miglietta L, Holmes A, Georgiou P, Rodriguez Manzano Jet al., 2020, High-level multiplexing in digital PCR with intercalating dyes by coupling real-time kinetics and melting curve analysis., Analytical Chemistry, Vol: 92, Pages: 14181-14188, ISSN: 0003-2700

Digital polymerase chain reaction (dPCR) is a mature technique that has enabled scientific breakthroughs in several fields. However, this technology is primarily used in research environments with high-level multiplexing representing a major challenge. Here, we propose a novel method for multiplexing, referred to as amplification and melting curve analysis (AMCA), which leverages the kinetic information in real-time amplification data and the thermodynamic melting profile using an affordable intercalating dye (EvaGreen). The method trains a system comprised of supervised machine learning models for accurate classification, by virtue of the large volume of data from dPCR platforms. As a case study, we develop a new 9-plex assay to detect mobilised colistin resistant (mcr) genes as clinically relevant targets for antimicrobial resistance. Over 100,000 amplification events have been analysed, and for the positive reactions, the AMCA approach reports a classification accuracy of 99.33 ± 0.13%, an increase of 10.0% over using melting curve analysis. This work provides an affordable method of high-level multiplexing without fluorescent probes, extending the benefits of dPCR in research and clinical settings.

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, Vol: 92, Pages: 13134-13143, 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

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 (vol 9, 126, 2020), ANTIMICROBIAL RESISTANCE AND INFECTION CONTROL, Vol: 9, ISSN: 2047-2994

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, Journal of Global Antimicrobial Resistance, Vol: 22, Pages: 826-831, ISSN: 2213-7165

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

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, JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, Vol: 75, Pages: 2670-2676, ISSN: 0305-7453

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, JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, Vol: 75, Pages: 2681-2688, ISSN: 0305-7453

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

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, Vol: 72, Pages: 2490-2502, 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

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, Vol: 2020, Pages: 1-1, 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

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

Aanensen DM, Abudahab K, Adams A, Afifi S, Alam MT, Alderton A, Alikhan N-F, Allan J, Almsaud M, Alrezaihi A, Alruwaili M, Amato R, Andersson M, Angyal A, Aranday-Cortes E, Ariani C, Armstrong SD, Asamaphan P, Attwood S, Aydin A, Badhan A, Baker D, Baker P, Balcazar CE, Ball J, Barton AE, Bashton M, Baxter L, Beale M, Beaver C, Beckett A, Beer R, Beggs A, Bell A, Bellis KL, Bentley EG, Berriman M, Betteridge E, Bibby D, Bicknell K, Birchley A, Black G, Blane B, Bloomfield S, Bolt F, Bonsall DG, Bosworth A, Bourgeois Y, Boyd O, Bradshaw D, Breuer J, Bridgewater H, Brooks T, Broos A, Brown JR, Brown RL, Brunker K, Bucca G, Buck D, Bull M, Butcher E, Caddy SL, Caller LG, Cambell S, Carlile M, Carmichael S, Carrilero L, Castellano S, Chaloner J, Chand M, Chapman MR, Chappell J, Charles I, Chauhan AJ, Chawla A, Cheng E, Churcher CM, Clark G, Clark JJ, Collins J, Colquhoun R, Connor TR, Constantinidou C, Coombes J, Corden S, Cottrell S, Cowell A, Curran MD, Curran T, Dabrera G, Danesh J, Darby AC, de Cesare M, Martins LDO, de Silva TI, Debebe B, Dervisevic S, Dewar RA, Dia M, Dorman M, Dougan G, Dover L, Downing F, Drury E, du Plessis L, Dyal PL, Eccles R, Edwards S, Ellaby N, Elliott S, Eltringham G, Elumogo N, Essex S, Evans CM, Evans J, Nascimento FF, Fairley DJ, Farr B, Feltwell T, Ferguson N, Filipe ADS, Findlay J, Forrest LM, Forrest S, Foulser L, Francois S, Fraser C, Frost L, Gallagher E, Gallagher MD, Garcia-Dorival I, Gaskin A, Gatica-Wilcox B, Gavriil A, Geidelberg L, Gemmell M, Gerada A, Gifford L, Gilbert L, Gilmore P, Gilroy R, Girgis S, Glaysher S, Golubchik T, Goncalves S, Goodfellow I, Goodwin S, Graham C, Graham L, Grammatopoulos D, Green A, Green LR, Greenaway J, Gregory R, Groves DC, Groves N, Guest M, Gunson R, Haldenby S, Hall G, Hamilton WL, Han X, Harris KA, Harrison EM, Hartley C, Herrera C, Hesketh A, Heyburn D, Hill V, Hiscox JA, Holden M, Holmes A, Holmes N, Holt GS, Hopes R, Hosmillo M, Houldcroft CJ, Howson-Wells H, Hubb J, Hughe J, Hughes Met al., 2020, An integrated national scale SARS-CoV-2 genomic surveillance network, The Lancet Microbe, Vol: 1, Pages: E99-E100, ISSN: 2666-5247

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

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

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

Rodriguez-Manzano J, Malpartida-Cardenas K, Moser N, Pennisi I, Cavuto M, Miglietta L, Moniri A, Penn R, Satta G, Randell P, Davies F, Bolt F, Barclay W, Holmes A, Georgiou Pet al., 2020, A handheld point-of-care system for rapid detection of SARS-CoV-2 in under 20 minutes

<jats:title>Abstract</jats:title><jats:p>The COVID-19 pandemic is a global health emergency characterized by the high rate of transmission and ongoing increase of cases globally. Rapid point-of-care (PoC) diagnostics to detect the causative virus, SARS-CoV-2, are urgently needed to identify and isolate patients, contain its spread and guide clinical management. In this work, we report the development of a rapid PoC diagnostic test (&lt; 20 min) based on reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) and semiconductor technology for the detection of SARS-CoV-2 from extracted RNA samples. The developed LAMP assay was tested on a real-time benchtop instrument (RT-qLAMP) showing a lower limit of detection of 10 RNA copies per reaction. It was validated against 183 clinical samples including 127 positive samples (screened by the CDC RT-qPCR assay). Results showed 90.55% sensitivity and 100% specificity when compared to RT-qPCR and average positive detection times of 15.45 ± 4.43 min. For validating the incorporation of the RT-LAMP assay onto our PoC platform (RT-eLAMP), a subset of samples was tested (n=40), showing average detection times of 12.89 ± 2.59 min for positive samples (n=34), demonstrating a comparable performance to a benchtop commercial instrument. Paired with a smartphone for results visualization and geo-localization, this portable diagnostic platform with secure cloud connectivity will enable real-time case identification and epidemiological surveillance.</jats:p><jats:sec><jats:title>One Sentence Summary</jats:title><jats:p>We demonstrate isothermal detection of SARS-CoV-2 in under 20 minutes from extracted RNA samples with a handheld Lab-on-Chip platform.</jats:p></jats:sec>

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

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

<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Evaluation of SARS-CoV-2 surface and air contamination during the COVID-19 pandemic in London.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>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 m<jats:sup>3</jats:sup>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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 i 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 (&gt;30) indicated that the virus would not be culturable.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>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 o

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, Vol: 71, Pages: 2459-2468, 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

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