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  • Journal article
    Abdolrasouli A, Petrou MA, Park H, Rhodes J, Rawson T, Moore L, Donaldson H, Holmes A, Fisher M, Armstrong-James Det al., 2018,

    Surveillance for azole-resistant Aspergillus fumigatus in a centralized diagnostic mycology service, London, United Kingdom, 1998-2017

    , Frontiers in Microbiology, Vol: 9, ISSN: 1664-302X

    Background/Objectives: Aspergillus fumigatus is the leading cause of invasive aspergillosis. Treatment is hindered by the emergence of resistance to triazole antimycotic agents. Here, we present the prevalence of triazole resistance among clinical isolates at a major centralized medical mycology laboratory in London, United Kingdom, in the period 1998–2017.Methods: A large number (n = 1469) of clinical A. fumigatus isolates from unselected clinical specimens were identified and their susceptibility against three triazoles, amphotericin B and three echinocandin agents was carried out. All isolates were identified phenotypically and antifungal susceptibility testing was carried out by using a standard broth microdilution method.Results: Retrospective surveillance (1998–2011) shows 5/1151 (0.43%) isolates were resistant to at least one of the clinically used triazole antifungal agents. Prospective surveillance (2015–2017) shows 7/356 (2.2%) isolates were resistant to at least one triazole antifungals demonstrating an increase in incidence of triazole-resistant A. fumigatus in our laboratory. Among five isolates collected from 2015 to 2017 and available for molecular testing, three harbored TR34/L98H alteration in the cyp51A gene that are associated with the acquisition of resistance in the non-patient environment.Conclusion: These data show that historically low prevalence of azole resistance may be increasing, warranting further surveillance of susceptible patients.

  • Journal article
    Jauneikaite E, Kapatai G, Davies F, Gozar I, Coelho J, Bamford K, Simone B, Begum L, Katiyo S, Patel B, Hoffman P, Lamagni T, Brannigan ET, Holmes A, Kadhani T, Galletly T, Martin K, Lyall H, Chow Y, Godambe S, Chalker V, Sriskandan Set al., 2018,

    Serial clustering of late onset group B streptococcal infections in the neonatal unit - a genomic re-evaluation of causality

    , Clinical Infectious Diseases, Vol: 67, Pages: 854-860, ISSN: 1058-4838

    Background. Invasive Group B streptococcus (GBS) is a major cause of serious neonatal infection. Current strategies to reduce early onset GBS disease have no impact on late onset disease (LOD). Although GBS is a normal part of the enteric microbiota in healthy term infants, LOD cases arising in the neonatal intensive care unit setting raise questions about mode of acquisition.Methods. Enhanced surveillance for any case of late onset GBS sepsis admitted to a level 3, 24-bed neonatal intensive care unit over a 2 year period was instituted following a cluster of four cases. All late onset GBS isolates were serotyped and genomes sequenced. Rectal screening of neonates for GBS was undertaken weekly. Healthcare workers and parents were not screened.Results. Over 24 months, a total of 12 late onset invasive GBS episodes were identified (incidence 0.6/1000 live births). Genomic analysis revealed that 11/12 GBS isolates (92%) were linked to at least one other LOD isolate. Four isolates from the first cluster were serotype V, resistant to macrolides and lincosamides, providing early evidence of a common source. Sequencing confirmed isolates were indistinguishable, or distinguishable by 1 SNP, from each other, and distinct from contemporary serotype V GBS. Although a common environmental source was not identified, prompt infection prevention interventions were instituted and no further serotype V GBS infections arose. Prospective surveillance identified three further clusters of LOD due to serotypes Ia, Ib, and III, leading to re-evaluation of interventions required for preventing GBS LOD. Conclusion. Acquisition routes for LOD GBS in the neonatal unit are poorly understood; such cases may not necessarily be sporadic. Within this neonatal unit, our data suggest that a single case of LOD GBS sepsis should be considered a potential nosocomial transmission event warranting prompt investigation, heightened infection prevention vigilance and action where required.

  • Conference paper
    Balinskaite V, Holmes A, Johnson A, Aylin Pet al., 2018,

    The Impact of a National Antimicrobial Stewardship Programmes on Antibiotic Prescribing in Primary Care in England: An Interrupted Time Series Analysis

    , ISQua, Publisher: OXFORD UNIV PRESS, Pages: 37-38, ISSN: 1353-4505
  • Conference paper
    Balinskaite V, Holmes A, Johnson A, Aylin Pet al., 2018,

    An Assessment of Unintended Consequences in England Following a National Antimicrobial Stewardship Programme: An Interrupted Time Series Analysis

    , ISQua, Publisher: OXFORD UNIV PRESS, Pages: 37-37, ISSN: 1353-4505
  • Journal article
    Courtenay M, Castro Sanchez EM, Deslandes R, Hodson K, Lim R, Morris G, Reeves S, Weiss Met al., 2018,

    Defining antimicrobial stewardship competencies for undergraduate health professional education in the United Kingdom: a study protocol

    , Journal of Interprofessional Care, Vol: 32, Pages: 638-640, ISSN: 1356-1820

    Drug resistant infections have been identified as one of the greatest threats to human health. With the increasing numbers of health professionals from nursing, pharmacy, and the allied health professions (including physiotherapists, podiatrists/chiropodists) involved in medicines management activities, including the prescription of antimicrobials, it is important that they are prepared for this role. This report presents a protocol for a study designed to provide national consensus on antimicrobial stewardship competencies appropriate for undergraduate professional education for these groups. A modified Delphi process will be used in which a panel of Experts comprising members from across England, Scotland and Wales, with expertise in the education and practice of healthcare professionals, antimicrobial prescribing and stewardship, interprofessional education and teamwork, will be invited to take part in two survey rounds to achieve consensus on stewardship competencies appropriate for undergraduate health professional education.

  • Journal article
    Mookerjee S, Dyakova E, Davies F, Bamford K, Brannigan ET, Holmes A, Otter JAet al., 2018,

    Evaluating serial screening cultures to detect carbapenemase-producing Enterobacteriaceae following hospital admission

    , JOURNAL OF HOSPITAL INFECTION, Vol: 100, Pages: 15-20, ISSN: 0195-6701
  • Journal article
    Lishman H, Costelloe C, Hopkins S, Johnson AP, Hope R, Guy R, Muller-Pebody B, Holmes A, Aylin Pet al., 2018,

    Exploring the relationship between primary care antibiotic prescribing for urinary tract infections, Escherichia coli bacteraemia incidence and antibiotic resistance: an ecological study

    , International Journal of Antimicrobial Agents, ISSN: 0924-8579
  • Journal article
    Knight GM, Costelloe C, Deeny S, Moore LSP, Hopkins S, Johnson A, Robotham J, Holmes Aet al., 2018,

    Quantifying where human acquisition of antibiotic resistance occurs: a mathematical modelling study

    , BMC Medicine, Vol: 16, ISSN: 1741-7015

    BackgroundAntibiotic-resistant bacteria (ARB) are selected by the use of antibiotics. The rational design of interventions to reduce levels of antibiotic resistance requires a greater understanding of how and where ARB are acquired. Our aim was to determine whether acquisition of ARB occurs more often in the community or hospital setting.MethodsWe used a mathematical model of the natural history of ARB to estimate how many ARB were acquired in each of these two environments, as well as to determine key parameters for further investigation. To do this, we explored a range of realistic parameter combinations and considered a case study of parameters for an important subset of resistant strains in England.ResultsIf we consider all people with ARB in the total population (community and hospital), the majority, under most clinically derived parameter combinations, acquired their resistance in the community, despite higher levels of antibiotic use and transmission of ARB in the hospital. However, if we focus on just the hospital population, under most parameter combinations a greater proportion of this population acquired ARB in the hospital.ConclusionsIt is likely that the majority of ARB are being acquired in the community, suggesting that efforts to reduce overall ARB carriage should focus on reducing antibiotic usage and transmission in the community setting. However, our framework highlights the need for better pathogen-specific data on antibiotic exposure, ARB clearance and transmission parameters, as well as the link between carriage of ARB and health impact. This is important to determine whether interventions should target total ARB carriage or hospital-acquired ARB carriage, as the latter often dominated in hospital populations.

  • Journal article
    Alividza V, Mariano V, Ahmad R, Charani E, Rawson T, Holmes A, Castro Sanchez EMet al., 2018,

    Investigating the impact of poverty on colonization and infection with drug-resistant organisms in humans: a systematic review

    , Infectious Diseases of Poverty, Vol: 7, ISSN: 2049-9957

    BackgroundPoverty increases the risk of contracting infectious diseases and therefore exposure to antibiotics. Yet there is lacking evidence on the relationship between income and non-income dimensions of poverty and antimicrobial resistance. Investigating such relationship would strengthen antimicrobial stewardship interventions.MethodsA systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Ovid, MEDLINE, EMBASE, Scopus, CINAHL, PsychINFO, EBSCO, HMIC, and Web of Science databases were searched in October 2016. Prospective and retrospective studies reporting on income or non-income dimensions of poverty and their influence on colonisation or infection with antimicrobial-resistant organisms were retrieved. Study quality was assessed with the Integrated quality criteria for review of multiple study designs (ICROMS) tool.ResultsNineteen articles were reviewed. Crowding and homelessness were associated with antimicrobial resistance in community and hospital patients. In high-income countries, low income was associated with Streptococcus pneumoniae and Acinetobacter baumannii resistance and a seven-fold higher infection rate. In low-income countries the findings on this relation were contradictory. Lack of education was linked to resistant S. pneumoniae and Escherichia coli. Two papers explored the relation between water and sanitation and antimicrobial resistance in low-income settings.ConclusionsDespite methodological limitations, the results suggest that addressing social determinants of poverty worldwide remains a crucial yet neglected step towards preventing antimicrobial resistance.

  • Journal article
    Knight GM, Dyakova E, Mookerjee S, Davies F, Brannigan E, Otter J, Holmes Aet al., 2018,

    Fast and expensive (PCR) or cheap and slow (culture)? A mathematical modelling study to explore screening for carbapenem resistance in UK hospitals

    , BMC Medicine, Vol: 16, ISSN: 1741-7015

    BackgroundEnterobacteriaceae are a common cause of hospital infections. Carbapenems are a clinically effective treatment of such infections. However, resistance is on the rise. In particular, carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) are increasingly common. In order to limit spread in clinical settings, screening and isolation is being recommended, but many different screening methods are available. We aimed to compare the impact and costs of three algorithms for detecting CP-CRE carriage.MethodsWe developed an individual-based simulation model to compare three screening algorithms using data from a UK National Health Service (NHS) trust. The first algorithm, “Direct PCR”, was highly sensitive/specific and quick (half a day), but expensive. The second, “Culture + PCR”, was relatively sensitive/specific but slower, requiring 2.5 days. A third algorithm, “PHE”, repeated the “Culture + PCR” three times with an additional PCR. Scenario analysis was used to compare several levels of CP-CRE prevalence and coverage of screening, different specialities as well as isolation strategies. Our outcomes were (1) days that a patient with CP-CRE was not detected and hence not isolated (“days at risk”), (2) isolation bed days, (3) total costs and (4) mean cost per CP-CRE risk day averted per year. We also explored limited isolation bed day capacity.ResultsWe found that although a Direct PCR algorithm would reduce the number of CP-CRE days at risk, the mean cost per CP-CRE risk day averted per year was substantially higher than for a Culture + PCR algorithm. For example, in our model of an intensive care unit, during a year with a 1.6% CP-CRE prevalence and 63% screening coverage, there were 508 (standard deviation 15), 642 (14) and 655 (14) days at risk under screening algorithms Direct PCR, Culture + PCR and PHE respectively, with mean costs per risk day averted of £192, £61 and

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Department of Medicine