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  • Journal article
    Taylor E, Sriskandan S, Woodford N, Hopkins Ket al., 2018,

    High prevalence of 16S rRNA methyltransferases among carbapenemase-producing Enterobacteriaceae in the UK & Ireland

    , International Journal of Antimicrobial Agents, Vol: 52, Pages: 278-282, ISSN: 0924-8579

    The emergence of 16S rRNA methyltransferases (16S RMTases) worldwide is a growing concern due to their ability to confer high-level resistance (MICs >256 mg/L) to all clinically-relevant aminoglycosides. As the occurrence of 16S RMTases in the United Kingdom has not been investigated to date, we screened 806 Enterobacteriaceae isolates displaying high-level aminoglycoside resistance (amikacin, gentamicin and tobramycin MICs ≥64, ≥32 and ≥32 mg/L, respectively) for 16S RMTases either by analysing whole-genome sequence (WGS) data (which were available for 449 isolates) or by PCR. A total of 94.5% (762/806) pan-aminoglycoside resistant Enterobacteriaceae were positive for one or more 16S RMTase genes; armA was the most common (340, 44.6%) followed by rmtC (146, 19.2%), rmtF (137, 18.0%), rmtB (87, 11.4%) and various two gene combinations (52, 6.8%). Most (93.4%; 712/762) 16S RMTase producers also carried acquired carbapenemase genes, with blaNDM the most common (592/712; 83.1%). Additionally, high-risk bacterial clones associated with blaNDM were identified in the subset of isolates with WGS data. These included E. coli sequence types (STs) 405 [21.8%, 19/87], 167 [20.7%, 18/87] 410 [12.6%, 11/87] and K. pneumoniae STs 14 [35.6%, 112/315], 231 [15.6%, 49/315] and 147 [10.5%, 33/315]. These accounted for 4.2% [15/358], 5.0% [18/358], 3.1% [11/358], 28.2% [101/358], 3.1% [11/358] and 7.0% [25/358] blaNDM-producing isolates, respectively. This study shows that 16S RMTases occur in the UK & Ireland and carbapenemases are particularly prevalent in 16S RMTase-producing Enterobacteriaceae. This association poses a risk to the treatment of multidrug-resistant Gram-negative infections in the clinical setting.

  • Journal article
    Castro Sanchez EM, Bennasar-Veny M, Smith M, Singleton S, Bennett E, Appleton J, Hamilton N, McEwen J, Gallagher Ret al., 2018,

    European Commission Guidelines for the prudent use of antimicrobials in human health: a missed opportunity to embrace nursing participation in stewardship

    , Clinical Microbiology and Infection, Vol: 24, Pages: 914-915, ISSN: 1198-743X

    Our letter highlights the shortcomings of recent EU Commission Guidelines for the prudent use of antimicrobials in human health in terms of the contribution of nurses towards stewardship. Such contribution has been advocated much more progressively in recent documents, which have also expanded the domains of the contribution to include domains other than clinical.

  • Journal article
    Abbara A, Rawson T, Karah N, El-Amin W, Hatcher J, Tajaldin B, Dar O, Dewachi O, Abu Sitta G, Uhlin BE, Sparrow Aet al., 2018,

    Antimicrobial resistance in the context of the Syrian conflict: drivers before and after the onset of conflict and key recommendations

    , International Journal of Infectious Diseases, Vol: 73, Pages: 1-6, ISSN: 1201-9712

    Current evidence describing antimicrobial resistance (AMR) in the context of the Syrian conflict is of poor quality and sparse in nature. This paper explores and reports the major drivers of AMR that were present in Syria pre-conflict and those that have emerged since its onset in March 2011. Drivers that existed before the conflict included a lack of enforcement of existing legislation to regulate over-the-counter antibiotics and notification of communicable diseases. This contributed to a number of drivers of AMR after the onset of conflict, and these were also compounded by the exodus of trained staff, the increase in overcrowding and unsanitary conditions, the increase in injuries, and economic sanctions limiting the availability of required laboratory medical materials and equipment. Addressing AMR in this context requires pragmatic, multifaceted action at the local, regional, and international levels to detect and manage potentially high rates of multidrug-resistant infections. Priorities are (1) the development of a competent surveillance system for hospital-acquired infections, (2) antimicrobial stewardship, and (3) the creation of cost-effective and implementable infection control policies. However, it is only by addressing the conflict and immediate cessation of the targeting of health facilities that the rehabilitation of the health system, which is key to addressing AMR in this context, can progress.

  • Journal article
    Rodriguez-Manzano J, Ying Chia P, Wen Yeo T, Holmes AH, Georgiou P, Yacoub Set al., 2018,

    Improving Dengue diagnostics and management through innovative technology

    , Current Infectious Disease Reports, Vol: 20, ISSN: 1534-3146

    Purpose of Review:Dengue continues to be a major global public health threat. Symptomatic infections can cause a spectrum of disease ranging from a mild febrile illness to severe and potentially life-threatening manifestations. Management relies on supportive treatment with careful fluid replacement. The purpose of this review is to define the unmet needs and challenges in current dengue diagnostics and patient monitoring and outline potential novel technologies to address these needs.Recent Findings:There have been recent advances in molecular and point-of-care (POC) diagnostics as well as technologies including wireless communication, low-power microelectronics, and wearable sensors that have opened up new possibilities for management, clinical monitoring, and real-time surveillance of dengue.Summary:Novel platforms utilizing innovative technologies for POC dengue diagnostics and wearable patient monitors have the potential to revolutionize dengue surveillance, outbreak response, and management at population and individual levels. Validation studies of these technologies are urgently required in dengue-endemic areas.

  • Journal article
    Rodriguez-Manzano J, Chia PY, Yeo TW, Holmes A, Georgiou P, Yacoub Set al., 2018,

    Improving Dengue Diagnostics and Management Through Innovative Technology (vol 20, 25, 2018)

    , CURRENT INFECTIOUS DISEASE REPORTS, Vol: 20, ISSN: 1523-3847
  • Journal article
    Blanco-Mavillard I, Bennasar-Veny M, De Pedro-Gómez J, Moya-Suarez A, Parra-García G, Rodríguez-Calero MA, Castro Sanchez EMet al., 2018,

    Implementation of a knowledge mobilization model to prevent peripheral venous catheter-related adverse events. PREBACP study: A multicenter cluster randomized trial protocol

    , Implementation Science, Vol: 13, ISSN: 1748-5908

    BackgroundPeripheral venous catheters are the most commonly used invasive devices in hospitals worldwide. Patients can experience multiple adverse events during the insertion, maintenance, and management of these devices. Health professionals aim to resolve the challenges of care variability in the use of peripheral venous catheter through adherence to clinical practice guidelines. The aim of this cluster-randomized controlled trial is to determine the efficacy of a multimodal intervention on incidence of adverse events associated with the use of peripheral venous catheters in adult hospital patients. Additional aims are to analyze the fidelity of nurses and the relationship between contextual factors on the use of best available and the outcomes of the intervention.MethodsFive public hospitals in the Spanish National Health System, with diverse profiles, including one university hospital and four second-level hospitals, will be included. In total, 20 hospitalization wards will be randomized for this study by ward to one of two groups. Those in the first group receive an intervention that lasts 12 months implementing evidence-based practice in healthcare related to peripheral catheters through a multimodal strategy, which will contain updated and poster protocols insertion, maintenance and removal of peripheral venous catheters, technologies applied to e-learning, feedback on the results, user and family information related to peripheral catheter, and facilitation of the best evidence by face-to-face training session. Primary outcome measures: Incidence of adverse events associated with the use of peripheral venous catheters is measured by assessing hospital records. Secondary outcome measures: Nurses’ adherence to clinical practice guidelines, clinical outcomes, and the cost of implementing the multimodal intervention.DiscussionClinical implementation is a complex, multifaceted phenomenon which requires a deep understanding of decision-making, knowledge mobil

  • Journal article
    Castro Sanchez EM, Iwami M, Ahmad R, Atun R, Holmes Aet al., 2018,

    Articulating citizen participation in national antimicrobial resistance plans: a comparison of European countries

    , European Journal of Public Health, ISSN: 1101-1262

    BackgroundNational action plans determine country responses to anti-microbial resistance (AMR). These plans include interventions aimed at citizens. As the language used in documents could persuade certain behaviours, we sought to assess the positioning and implied responsibilities of citizens in current European AMR plans. This understanding could lead to improved policies and interventions.MethodsReview and comparison of national action plans for AMR (NAP-AMR) obtained from the European Centre for Disease Prevention and Control (plans from 28 European Union and four European Economic Area/European Free Trade Association countries), supplemented by European experts (June–September 2016). To capture geographical diversity, 11 countries were purposively sampled for content and discourse analyses using frameworks of lay participation in healthcare organization, delivery and decision-making.ResultsCountries were at different stages of NAP-AMR development (60% completed, 25% in-process, 9% no plan). The volume allocated to citizen roles in the plans ranged from 0.3 to 18%. The term ‘citizen’ was used by three countries, trailing behind ‘patients’ and ‘public’ (9/11), ‘general population’ (6/11) and ‘consumers’ (6/11). Increased citizen awareness about AMR was pursued by ∼2/3 plans. Supporting interventions included awareness campaigns (11/11), training/education (7/11) or materials during clinical encounters (4/11). Prevention of infection transmission or self-care behaviours were much less emphasized. Personal/individual and social/collective role perspectives seemed more frequently stimulated in Nordic countries.ConclusionCitizen roles in AMR plans are not fully articulated. Documents could employ direct language to emphasise social or collective responsibilities in optimal antibiotic use.

  • Journal article
    Puaar SJ, Franklin BD, 2018,

    Impact of an inpatient electronic prescribing system on prescribing error causation: a qualitative evaluation in an English hospital

    , BMJ QUALITY & SAFETY, Vol: 27, Pages: 529-538, ISSN: 2044-5415
  • Journal article
    Nellums LB, Thompson H, Holmes A, Castro-Sánchez E, Otter JA, Norredam M, Friedland JS, Hargreaves Set al., 2018,

    Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

    , Lancet Infectious Diseases, Vol: 18, Pages: 796-811, ISSN: 1473-3099

    BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus

  • Journal article
    Rawson T, Charani E, Moore L, Gilchrist M, Georgiou P, Hope W, Holmes Aet al., 2018,

    Exploring the use of C-Reactive Protein to Estimate the Pharmacodynamics of Vancomycin

    , Therapeutic Drug Monitoring, Vol: 40, Pages: 315-321, ISSN: 0163-4356

    BackgroundC-reactive protein (CRP) pharmacodynamic (PD) models have the potential to provide adjunctive methods for predicting the individual exposure-response to antimicrobial therapy. We investigated CRP PD linked to a vancomycin PK model using routinely collected data from non-critical care adults in secondary care.MethodsPatients receiving intermittent intravenous vancomycin therapy in secondary care were identified. A two-compartment vancomycin PK model was linked to a previously described PD model describing CRP response. PK and PD parameters were estimated using a Non-Parametric Adaptive Grid technique. Exposure-response relationships were explored with vancomycin area-under-the-curve (AUC) and the index, AUC:EC50, fitted to CRP data using a sigmoidal Emax model. ResultsTwenty-nine individuals were included. Median age was 62 (21-97) years. Fifteen (52%) patients were microbiology confirmed. PK and PD models were adequately fitted (r2 0.83 and 0.82 respectively). There was a wide variation observed in individual Bayesian posterior EC50 estimates (6.95-48.55mg/L), with mean (SD) AUC:EC50 of 31.46 (29.22). AUC:EC50 was fitted to terminal CRP with AUC:EC50 >19 associated with lower CRP value at 96-120 hours of therapy (100mg/L vs. 44mg/L; p<0.01). ConclusionThe use of AUC:EC50 has the potential to provide in-vivo organism and host response data as an adjunct for in-vitro MIC data, which is currently used as the gold standard PD index for vancomycin therapy. This index can be estimated using routinely collected clinical data. Future work must investigate the role of AUC:EC50 in a prospective cohort and explore linkage with direct patient outcomes.

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Department of Medicine