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  • Journal article
    Afshar B, Turner CE, Lamagni TL, Smith K, Al-Shahib A, Underwood A, Holden MTG, Efstratiou A, Sriskandan Set al., 2017,

    Enhanced nasopharyngeal infection and shedding associated with an epidemic lineage of emm3 group A Streptococcus

    , Virulence, Vol: 8, Pages: 1390-1400, ISSN: 2150-5608

    Background: A group A Streptococcus (GAS) lineage of genotype emm3, sequence type 15 (ST15) was associated with a 6 month upsurge in invasive GAS disease in the UK. The epidemic lineage (Lineage C) had lost 2 typical emm3 prophages, Φ315.1 and Φ315.2 associated with the superantigen ssa, but gained a different prophage (ΦUK-M3.1) associated with a different superantigen, speC and a DNAse spd1. Methods and Results: The presence of speC and spd1 in Lineage C ST15 strains enhanced both in vitro mitogenic and DNase activities over non-Lineage C ST15 strains. Invasive disease models in Galleria mellonella and SPEC-sensitive transgenic mice, revealed no difference in overall invasiveness of Lineage C ST15 strains compared with non-Lineage C ST15 strains, consistent with clinical and epidemiological analysis. Lineage C strains did however markedly prolong murine nasal infection with enhanced nasal and airborne shedding compared with non-Lineage C strains. Deletion of speC or spd1 in 2 Lineage C strains identified a possible role for spd1 in airborne shedding from the murine nasopharynx. Conclusions: Nasopharyngeal infection and shedding of Lineage C strains was enhanced compared with non-Lineage C strains and this was, in part, mediated by the gain of the DNase spd1 through prophage acquisition.

  • Journal article
    Pereira N, Castro Sanchez EM, Nathwani D, 2017,

    How can multi-professional education support better stewardship?

    , Infectious Disease Reports, Vol: 9, ISSN: 2036-7449

    Antimicrobial stewardship is widely accepted as an efficient strategy to combat the growing threat of antimicrobial resistance. Education is one of the cornerstones of successful antimicrobial stewardship programs. There is also general agreement that antimicrobial stewardship is a team effort that must involve the whole continuum of healthcare workers. Providing adequate education for all different professionals although challenging is deemed crucial to achieve good results. This paper reviews the different strategies available to educate the multiple healthcare workers, discusses how education can improve antimicrobial stewardship programs and outlines some of the challenges faced and research gaps that need to be addressed in order to improve education in this field.

  • Journal article
    Pearson M, Fallowfield JL, Davey T, Thorpe N, Allsopp A, Shaw A, Wilson D, Sriskandan S, Lamb Let al., 2017,

    Asymptomatic group A Streptococcal throat carriage in Royal Marines recruits and young officers

    , Journal of Infection, Vol: 74, Pages: 585-589, ISSN: 1532-2742

    Aims A prospective observational study was conducted in Royal Marines (RM) recruits to investigate throat carriage of group A Streptococcus (GAS) and incidence of soft tissue infections. Methods 1012 RM recruits were followed through a 32-week training programme, with throat swabs being obtained in weeks 1, 6, 15, and 32. Alongside a separate cohort of 46 RM Young Officers (YO) undergoing training were sampled in parallel. Results Carriage of group A Streptococcus was detected in only 5/1012 (0.49%) recruits at the beginning of training and remained low throughout training. There was no association between GAS carriage and development of soft tissue infection. There was no carriage of GAS in the smaller YO cohort at the start of training, (0/46). At week 6, a surge in GAS carriage was detected in 8/46 (17%) YO, that could be ascribed to a cluster of GAS genotype emm83. Conclusions Asymptomatic GAS carriage is very infrequent among young adults in England and this should be borne in mind when considering the relevance of a positive throat swab result in symptomatic patients or outbreaks. Despite low prevalence, there is however potential for GAS to rapidly and transiently disseminate among adults during outbreaks.

  • Journal article
    Micallef C, Chaudhry NT, Holmes AH, Hopkins S, Benn J, Franklin BDet al., 2017,

    Secondary use of data from hospital electronic prescribing and pharmacy systems to support the quality and safety of antimicrobial use: a systematic review

    , Journal of Antimicrobial Chemotherapy, Vol: 72, Pages: 1880-1885, ISSN: 1460-2091

    Background: Electronic prescribing (EP) and electronic hospital pharmacy (EHP) systems are increasingly common. A potential benefit is the extensive data in these systems that could be used to support antimicrobial stewardship, but there is little information on how such data are currently used to support the quality and safety of antimicrobial use.Objectives: To summarize the literature on secondary use of data (SuD) from EP and EHP systems to support quality and safety of antimicrobial use, to describe any barriers to secondary use and to make recommendations for future work in this field.Methods: We conducted a systematic search within four databases; we included original research studies that were (1) based on SuD from hospital EP or EHP systems and (2) reported outcomes relating to quality and/or safety of antimicrobial use and/or qualitative findings relating to SuD in this context.Results: Ninety-four full-text articles were obtained; 14 met our inclusion criteria. Only two described interventions based on SuD; seven described SuD to evaluate other antimicrobial stewardship interventions and five described descriptive or exploratory studies of potential applications of SuD. Types of data used were quantitative antibiotic usage data (n = 9 studies), dose administration data (n = 4) and user log data from an electronic dashboard (n = 1). Barriers included data access, data accuracy and completeness, and complexity when using data from multiple systems or hospital sites.Conclusions: The literature suggests that SuD from EP and EHP systems is potentially useful to support or evaluate antimicrobial stewardship activities; greater system functionality would help to realize these benefits.

  • Journal article
    Charani E, Tarrant C, Moorthy K, Sevdalis N, Brennan L, Holmes AHet al., 2017,

    Understanding antibiotic decision making in surgery-a qualitative analysis.

    , Clinical Microbiology and Infection, Vol: 23, Pages: 752-760, ISSN: 1469-0691

    OBJECTIVE: To investigate the characteristics and culture of antibiotic decision making in the surgical specialty. METHODS: A qualitative study including ethnographic observation and face-to-face interviews with participants from six surgical teams at a teaching hospital in London was conducted. Over a 3-month period: (a) 30 ward rounds (WRs) (100 h) were observed, (b) face-to-face follow-up interviews took place with 13 key informants, (c) multidisciplinary meetings on the management of surgical patients and daily practice on wards were observed. Applying these methods provided rich data for characterizing the antibiotic decision making in surgery and enabled cross-validation and triangulation of the findings. Data from the interview transcripts and the observational notes were coded and analysed iteratively until saturation was reached. RESULTS: The surgical team is in a state of constant flux with individuals having to adjust to the context in which they work. The demands placed on the team to be in the operating room, and to address the surgical needs of the patient mean that the responsibility for antibiotic decision making is uncoordinated and diffuse. Antibiotic decision making is considered by surgeons as a secondary task, commonly delegated to junior members of their team and occurs in the context of disjointed communication. CONCLUSION: There is lack of clarity around medical decision making for treating infections in surgical patients. The result is sub-optimal and uncoordinated antimicrobial management. Developing the role of a perioperative clinician may help to improve patient-level outcomes and optimize decision making.

  • Journal article
    Rawson T, moore L, Hernandez B, Charani E, Castro Sanchez E, Herrero P, Hayhoe B, Hope W, Georgiou P, Holmes Aet al., 2017,

    A systematic review of clinical decision support systems for antimicrobial management: Are we failing to investigate these interventions appropriately?

    , Clinical Microbiology and Infection, Vol: 23, Pages: 524-532, ISSN: 1469-0691

    ObjectivesClinical decision support systems (CDSS) for antimicrobial management can support clinicians to optimise antimicrobial therapy. We reviewed all original literature (qualitative and quantitative) to understand the current scope of CDSS for antimicrobial management and analyse existing methods used to evaluate and report such systems. MethodPRISMA guidelines were followed. Medline, EMBASE, HMIC Health and Management, and Global Health databases were searched from 1st January 1980 to 31st October 2015. All primary research studies describing CDSS for antimicrobial management in adults in primary or secondary care were included. For qualitative studies, thematic synthesis was performed. Quality was assessed using Integrated quality Criteria for the Review Of Multiple Study designs (ICROMS) criteria. CDSS reporting was assessed against a reporting framework for behaviour change intervention implementation.ResultsFifty-eight original articles were included describing 38 independent CDSS. The majority of systems target antimicrobial prescribing (29/38;76%), are platforms integrated with electronic medical records (28/38;74%), and have rules based infrastructure providing decision support (29/38;76%). On evaluation against the intervention reporting framework, CDSS studies fail to report consideration of the non-expert, end-user workflow. They have narrow focus, such as antimicrobial selection, and use proxy outcome measures. Engagement with CDSS by clinicians was poor.ConclusionGreater consideration of the factors that drive non-expert decision making must be considered when designing CDSS interventions. Future work must aim to expand CDSS beyond simply selecting appropriate antimicrobials with clear and systematic reporting frameworks for CDSS interventions developed to address current gaps identified in the reporting of evidence.

  • Journal article
    Holmes AH, Carruthers J, Majeed A, 2017,

    A suspected viral rash in pregnancy

    , The BMJ, Vol: 356, ISSN: 2044-6055
  • Journal article
    Charani E, Gharbi M, Moore LSP, Castro Sanchez E, Lawson W, Gilchrist M, Holmes AHet al., 2017,

    The effect of adding a mobile health intervention to a multimodal antimicrobial stewardship programme across three teaching hospitals – an interrupted time series study

    , Journal of Antimicrobial Chemotherapy, Vol: 72, Pages: 1825-1831, ISSN: 1460-2091

    Objectives To evaluate the impact of adding a mobile health (mHealth) decision support system for antibiotic prescribing to an established antimicrobial stewardship programme (ASP). Methods In August 2011, the antimicrobial prescribing policy was converted into a mobile application (app). A segmented regression analysis of interrupted time series was used to assess the impact of the app on prescribing indicators using data (2008-2014) from a biannual point prevalence study (PPS) in medicine and surgery wards. There were six data points pre and six data points post-implementation. Results There was an increase in compliance with policy (e.g. compliance with empirical therapy or expert advice) in medicine (6.48%, CI -1.25—14.20) and surgery (6.63%, CI 0.15—13.10) in the implementation period, with a significant sudden change in level in surgery (p<0.05). There was an increase, though not significant, in medicine (15.20%, CI 17.81—48.22) and surgery (35.97%, -3.72—75.66) in the percentage of prescriptions that had a stop/review date documented. The documentation of indication decreased in both medicine (-16.25%, CI -42.52—10.01) and surgery (-14.62%, CI -42.88—13.63).Conclusion Introducing the ‘app’ to an existing ASP had a significant impact on the compliance to policy in surgery, and a positive but not significant effect on documentation of stop/review date in both specialties. The negative effect on the third indicator may have been due to existing ASP efforts. The broader value of providing an antimicrobial policy on a digital platform e.g. the reach and access to the policy, should be measured using indicators more sensitive to mHealth interventions.

  • Journal article
    Holmes AH, Boyd SE, Moore LSP, Gilchrist M, Costelloe C, Castro Sanchez E, Franklin BDet al., 2017,

    Obtaining antibiotics online from within the UK: a cross-sectional study

    , Journal of Antimicrobial Chemotherapy, ISSN: 1460-2091
  • Journal article
    Rawson T, Moore L, Tivey A, Tsao A, Gilchrist M, Charani E, Holmes Aet al., 2017,

    Behaviour change interventions to influence antimicrobial prescribing: a cross-sectional analysis of reports from UK state-of-the-art scientific conferences

    , Antimicrobial Resistance and Infection Control, Vol: 6, ISSN: 2047-2994

    BackgroundTo improve the quality of antimicrobial stewardship (AMS) interventions the application of behavioural sciences supported by multidisciplinary collaboration has been recommended. We analysed major UK scientific research conferences to investigate AMS behaviour change intervention reporting. MethodsLeading UK 2015 scientific conference abstracts for 30 clinical specialties were identified and interrogated. All AMS and/or antimicrobial resistance(AMR) abstracts were identified using validated search criteria. Abstracts were independently reviewed by four researchers with reported behavioural interventions classified using a behaviour change taxonomy. ResultsConferences ran for 110 days with >57,000 delegates. 311/12,313(2.5%) AMS-AMR abstracts (oral and poster) were identified. 118/311(40%) were presented at the UK’s infectious diseases/microbiology conference. 56/311(18%) AMS-AMR abstracts described behaviour change interventions. These were identified across 12/30(40%) conferences. The commonest abstract reporting behaviour change interventions were quality improvement projects [44/56 (79%)]. In total 71 unique behaviour change functions were identified. Policy categories; “guidelines” (16/71) and “service provision” (11/71) were the most frequently reported. Intervention functions; “education” (6/71), “persuasion” (7/71), and “enablement” (9/71) were also common. Only infection and primary care conferences reported studies that contained multiple behaviour change interventions. The remaining 10 specialties tended to report a narrow range of interventions focusing on “guidelines” and “enablement”. ConclusionDespite the benefits of behaviour change interventions on antimicrobial prescribing, very few AMS-AMR studies reported implementing them in 2015. AMS interventions must focus on promoting behaviour change towards antimicrobial prescribing. Greater focus must b

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Department of Medicine