Publications
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Balinskaite V, Holmes A, Johnson A, et 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
Zemanick ET, Burgel P-R, Byrnes C, et al., 2018, RECOMMENDATIONS FOR USE OF ANTIMICROBIAL RESISTANCE TESTING IN CLINICAL PRACTICE, Publisher: WILEY, Pages: 59-61, ISSN: 8755-6863
Mookerjee S, Dyakova E, Davies F, et 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
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- Citations: 8
Lishman H, Costelloe C, Hopkins S, et 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
Knight GM, Costelloe C, Deeny S, et 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.
Alividza V, Mariano V, Ahmad R, et 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.
Knight GM, Dyakova E, Mookerjee S, et 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
Rodriguez-Manzano J, Chia PY, Yeo TW, et al., 2018, Improving Dengue Diagnostics and Management Through Innovative Technology (vol 20, 25, 2018), CURRENT INFECTIOUS DISEASE REPORTS, Vol: 20, ISSN: 1523-3847
Rodriguez-Manzano J, Ying Chia P, Wen Yeo T, et 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.
Rawson TM, Gowers S, Rogers M, et al., 2018, Towards a minimally invasive device for continuous monitoring of beta-lactam antibiotics, Publisher: ELSEVIER SCI LTD, Pages: 109-109, ISSN: 1201-9712
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- Citations: 1
Castro Sanchez EM, Iwami M, Ahmad R, et 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.
Hansen S, Schwab F, Gastmeier P, et al., 2018, Association of national and hospital factors to hospitals' alcohol-based handrub consumption in Europe: results of the European PROHIBIT study, CLINICAL MICROBIOLOGY AND INFECTION, Vol: 24, ISSN: 1198-743X
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- Citations: 4
Bou-Antoun S, Costelloe C, Honeyford CE, et al., 2018, Age-related decline in antibiotic prescribing for uncomplicated respiratory tract infections in primary care in England following the introduction of a national financial incentive (the Quality Premium) for health commissioners to reduce use of antibiotics in the community: an interrupted time series analysis, Journal Of Antimicrobial Chemotherapy, ISSN: 0305-7453
ObjectivesTo assess the impact of the 2015/16 NHS England Quality Premium (which provided a financial incentive for Clinical Commissioning Groups to reduce antibiotic prescribing in primary care) on antibiotic prescribing by General Practitioners (GPs) for respiratory tract infections (RTIs).MethodsInterrupted time series analysis using monthly patient-level consultation and prescribing data obtained from the Clinical Practice Research Datalink (CPRD) between April 2011 and March 2017. The study population comprised patients consulting a GP who were diagnosed with an RTI. We assessed the rate of antibiotic prescribing in patients (both aggregate and stratified by age) with a recorded diagnosis of uncomplicated RTI, before and after the implementation of the Quality Premium.ResultsPrescribing rates decreased over the 6 year study period, with evident seasonality. Notably, there was a 3% drop in the rate of antibiotic prescribing (equating to 14.65 prescriptions per 1000 RTI consultations) (P < 0.05) in April 2015, coinciding with the introduction of the Quality Premium. This reduction was sustained, such that after 2 years there was a 3% decrease in prescribing relative to that expected had the pre-intervention trend continued. There was also a concurrent 2% relative reduction in the rate of broad-spectrum antibiotic prescribing. Antibiotic prescribing for RTIs diagnosed in children showed the greatest decline with a 6% relative change 2 years after the intervention. Of the RTI indications studied, the greatest reductions in antibiotic prescribing were seen for patients with sore throats.ConclusionsCommunity prescribing of antibiotics for RTIs significantly decreased following the introduction of the Quality Premium, with the greatest reduction seen in younger patients.
Fukuda K, Limmathurotsakul D, Okeke IN, et al., 2018, Surveillance and Epidemiology of Drug Resistant Infections Consortium (SEDRIC): Supporting the transition from strategy to action, Wellcome Open Research, Vol: 3, Pages: 59-59
<ns3:p>In recognition of the central importance of surveillance and epidemiology in the control of antimicrobial resistance and the need to strengthen surveillance at all levels, Wellcome has brought together a new international expert group SEDRIC (Surveillance and Epidemiology of Drug Resistant Infections Consortium). SEDRIC aims to advance and transform the ways of tracking, sharing and analysing rates of infection and antimicrobial resistance, burden of disease, information on antimicrobial use, opportunities for preventative measures such as vaccines, and contamination of the environment. SEDRIC aims to strengthen the availability of information needed to monitor and track risks, including an evaluation of access to, and utility of data generated by pharma and research activities, and will support the translation of surveillance data into interventions, changes in policy and more effective practices. Ways of working will include the provision of independent scientific analysis, advocacy and expert advice to groups, such as the Wellcome Drug Resistant Infection Priority Programme. A priority for SEDRIC’s first Working Group is to review mechanisms to strengthen the generation, collection, collation and dissemination of high quality data, together with finding more effective and creative uses of existing data and proxy measures, and linking such approaches to existing in-country capabilities. SEDRIC will also promote the translation of technological innovations into public health solutions.</ns3:p>
WHO, Castro Sanchez E, Holmes A, 2018, WHO competency framework for health workers’ education and training on antimicrobial resistance, Geneva, Switzerland, Publisher: World Health Organization, WHO/HIS/HWF/AMR/2018.1
In support of WHO and Member States efforts to implement the Global Action plan on Antimicrobial Resistance (GAP AMR), WHO has published a competency framework for health workers’ education and training on antimicrobial resistance (AMR). The competency framework is one of several products being developed by WHO in collaboration with partners and leading research institutions to address the first objective of the GAP AMR, which is to improve awareness and understanding of AMR through effective communication, education and training.The framework is a matrix menu of core and additional knowledge, skills and attitudes for health workers in the field of human health. It is designed to be used as a reference guide and applied according to local priorities and needs. The ultimate aim is to ensure that all health workers are equipped with the requisite competencies at pre-service education and in-service training levels to address AMR in policy and practice settings.
Nellums LB, Thompson H, Holmes A, et 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
Rawson T, Charani E, Moore L, et 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.
Hansen S, Schwab F, Zingg W, et al., 2018, Process and outcome indicators for infection control and prevention in European acute care hospitals in 2011 to 2012-Results of the PROHIBIT study, EUROSURVEILLANCE, Vol: 23, Pages: 24-33, ISSN: 1560-7917
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- Citations: 14
Fukuda K, Limmathurotsakul D, Okeke IN, et al., 2018, Surveillance and Epidemiology of Drug Resistant Infections Consortium (SEDRIC): supporting the transition from strategy to action, Wellcome Open Research, Vol: 3, ISSN: 2398-502X
In recognition of the central importance of surveillance and epidemiology in the control of antimicrobial resistance and the need to strengthen surveillance at all levels, Wellcome has brought together a new international expert group SEDRIC (Surveillance and Epidemiology of Drug Resistant Infections Consortium). SEDRIC aims to advance and transform the ways of tracking, sharing and analysing rates of infection and drug resistance, burden of disease, information on antibiotic use, opportunities for preventative measures such as vaccines, and contamination of the environment. SEDRIC will strengthen the availability of information needed to monitor and track risks, including an evaluation of access to, and utility of data generated by pharma and research activities, and will support the translation of surveillance data into interventions, changes in policy and more effective practices. Ways of working will include the provision of independent scientific analysis, advocacy and expert advice to groups, such as the Wellcome Drug Resistant Infection Priority Programme. A priority for SEDRIC's first Working Group is to review mechanisms to strengthen the generation, collection, collation and dissemination of high quality data, together with the need for creativity in the use of existing data and proxy measures, and linking to existing in-country networking infrastructure. SEDRIC will also promote the translation of technological innovations into public health solutions.
Rawson T, o'hare D, Herrero P, et al., 2018, Delivering precision antimicrobial therapy through closed-loop control systems, Journal of Antimicrobial Chemotherapy, Vol: 73, Pages: 835-843, ISSN: 0305-7453
Sub-optimal exposure to antimicrobial therapy is associated with poor patient outcomes and the development of antimicrobial resistance. Mechanisms for optimizing the concentration of a drug within the individual patient are under development. However, several barriers remain in realizing true individualization of therapy. These include problems with plasma drug sampling, availability of appropriate assays, and current mechanisms for dose adjustment. Biosensor technology offers a means of providing real-time monitoring of antimicrobials in a minimally invasive fashion. We report the potential for using microneedle biosensor technology as part of closed-loop control systems for the optimization of antimicrobial therapy in individual patients.
Rawson T, Moore L, Castro Sanchez E, et al., 2018, Development of a patient-centred intervention to improve knowledge and understanding of antibiotic therapy in secondary care, Antimicrobial Resistance and Infection Control, Vol: 7, ISSN: 2047-2994
Introduction: We developed a personalised antimicrobial information module co-designed with patients. This study aimed to evaluate the potential impact of this patient-centred intervention on short-term knowledge and understanding of antimicrobial therapy in secondary care. Methods:Thirty previous patients who had received antibiotics in hospital within 12 months were recruited to co-design an intervention to promote patient engagement with infection management. Two workshops, containing five focus-groups were held. These were audio-recorded. Data were analysed using a thematic framework developed deductively based on previous work. Line-by-line coding was performed with new themes added to the framework by two researchers. This was used to inform the development of a patient information module, embedded within an electronic decision support tool (CDSS). The intervention was piloted over a four-week period at Imperial College Healthcare NHS Trust on 30 in-patients. Pre- and post-intervention questionnaires were developed and implemented to assess short term changes in patient knowledge and understanding and provide feedback on the intervention. Data were analysed using SPSS and NVIVO software. Results: Within the workshops, there was consistency in identified themes. The participants agreed upon and co-designed a personalised PDF document that could be integrated into an electronic CDSS to be used by healthcare professionals at the point-of-care. Their aim for the tool was to provide individualised practical information, signpost to reputable information sources, and enhance communication between patients and healthcare professionals.Eighteen out of thirty in-patients consented to participant in the pilot evaluation with 15/18(83%) completing the study. Median (range) age was 66(22-85) years. The majority were male (10/15;66%). Pre-intervention, patients reported desiring further information regarding their infections and antibiotic therapy, including side effects
Birgand G, Castro-Sánchez E, Hansen S, et al., 2018, Comparison of governance approaches for the control of antimicrobial resistance: Analysis of three European countries, Antimicrobial Resistance and Infection Control, Vol: 7, ISSN: 2047-2994
Policy makers and governments are calling for coordination to address the crisis emerging from the ineffectiveness of current antibiotics and stagnated pipe-line of new ones - antimicrobial resistance (AMR). Wider contextual drivers and mechanisms are contributing to shifts in governance strategies in health care, but are national health system approaches aligned with strategies required to tackle antimicrobial resistance? This article provides an analysis of governance approaches within healthcare systems including: priority setting, performance monitoring and accountability for AMR prevention in three European countries: England, France and Germany. Advantages and unresolved issues from these different experiences are reported, concluding that mechanisms are needed to support partnerships between healthcare professionals and patients with democratized decision-making and accountability via collaboration. But along with this multi-stakeholder approach to governance, a balance between regulation and persuasion is needed.
Holmes AH, 2018, anvoei;wan;iongawgawe, International Journal of Geographical Information Systems, ISSN: 0269-3798
Holmes AH, Holmes M, Gottlieb T, et al., 2018, End non-essential use of antimicrobials in livestock, BMJ, Vol: 360, ISSN: 0959-8138
Abbas M, 2018, Conflicts of interest in infection prevention and control research: no smoke without fire. A narrative review, Intensive Care Medicine, ISSN: 0342-4642
Hernandez Perez B, Herrero Viñas P, Miles Rawson T, et al., 2017, Supervised Learning for Infection Risk Inference Using Pathology Data, BMC Medical Informatics and Decision Making, Vol: 17, ISSN: 1472-6947
Background: Antimicrobial Resistance is threatening our ability to treat common infectious diseases and overuse of antimicrobials to treat human infections in hospitals is accelerating this process. Clinical Decision Support Systems (CDSSs) have been proven to enhance quality of care by promoting change in prescription practices through antimicrobial selection advice. However, bypassing an initial assessment to determine the existence of an underlying disease that justifies the need of antimicrobial therapy might lead to indiscriminate and often unnecessary prescriptions.Methods: From pathology laboratory tests, six biochemical markers were selected and combined with microbiology outcomes from susceptibility tests to create a unique dataset with over one and a half million daily profiles to perform infection risk inference. Outliers were discarded using the inter-quartile range rule and several sampling techniques were studied to tackle the class imbalance problem. The first phase selects the most effective and robust model during training using four-fold stratified cross-validation. The second phase evaluates the final model after isotonic calibration in scenarios with missing inputs and imbalanced class distributions. Results: More than 50\% of infected profiles have daily requested laboratory tests for the six biochemical markers with very promising infection inference results: area under the receiver operating characteristic curve (0.80-0.83), sensitivity (0.64-0.75) and specificity (0.92-0.97). Standardization consistently outperforms normalization and sensitivity is enhanced by using the SMOTE sampling technique. Furthermore, models operated without noticeable loss in performance if at least four biomarkers were available.Conclusion: The selected biomarkers comprise enough information to perform infection risk inference with a high degree of confidence even in the presence of incomplete and imbalanced data. Since they are commonly available in hospitals, Clini
Otter JA, Doumith M, Davies F, et al., 2017, Emergence and clonal spread of colistin resistance due to multiple mutational mechanisms in carbapenemase-producing Klebsiella pneumoniae in London, Scientific Reports, Vol: 7, ISSN: 2045-2322
Carbapenemase-producing Enterobacteriaceae (CPE) are emerging worldwide, limiting therapeutic options. Mutational and plasmid-mediated mechanisms of colistin resistance have both been reported. The emergence and clonal spread of colistin resistance was analysed in 40 epidemiologically-related NDM-1 carbapenemase producing Klebsiella pneumoniae isolates identified during an outbreak in a group of London hospitals. Isolates from July 2014 to October 2015 were tested for colistin susceptibility using agar dilution, and characterised by whole genome sequencing (WGS). Colistin resistance was detected in 25/38 (65.8%) cases for which colistin susceptibility was tested. WGS found that three potential mechanisms of colistin resistance had emerged separately, two due to different mutations in mgrB, and one due to a mutation in phoQ, with onward transmission of two distinct colistin-resistant variants, resulting in two sub-clones associated with transmission at separate hospitals. A high rate of colistin resistance (66%) emerged over a 10 month period. WGS demonstrated that mutational colistin resistance emerged three times during the outbreak, with transmission of two colistin-resistant variants.
Rawson TM, Sharma S, Georgiou P, et al., 2017, Towards a minimally invasive device for beta-lactam monitoring in humans, Electrochemistry Communications, Vol: 82, Pages: 1-5, ISSN: 1388-2481
Antimicrobial resistance is a leading patient safety issue. There is a need to develop novel mechanisms for monitoring and subsequently improving the precision of how we use antibiotics. A surface modified microneedle array was developed for monitoring beta-lactam antibiotic levels in human interstitial fluid. The sensor was fabricated by anodically electrodepositing iridium oxide (AEIROF) onto a platinum surface on the microneedle followed by fixation of beta-lactamase enzyme within a hydrogel. Calibration of the sensor was performed to penicillin-G in buffer solution (PBS) and artificial interstitial fluid (ISF). Further calibration of a platinum disc electrode was undertaken using amoxicillin and ceftriaxone. Open-circuit potentials were performed and data analysed using the Hill equation and log(concentration [M]) plots. The microneedle sensor demonstrated high reproducibility between penicillin-G runs in PBS with mean Km (± 1SD) = 0.0044 ± 0.0013 M and mean slope function of log(concentration plots) 29 ± 1.80 mV/decade (r2 = 0.933). Response was reproducible after 28 days storage at 4 °C. In artificial ISF, the sensors response was Km (± 1SD) = 0.0077 ± 0.0187 M and a slope function of 34 ± 1.85 mv/decade (r2 = 0.995). Our results suggest that microneedle array based beta-lactam sensing may be a future application of this AEIROF based enzymatic sensor.
Knight GM, Costelloe C, Murray KA, et al., 2017, Addressing the unknowns of antimicrobial resistance: quantifying and mapping the drivers of burden, Clinical Infectious Diseases, Vol: 66, Pages: 612-616, ISSN: 1058-4838
The global threat of antimicrobial resistance (AMR) has arisen through a network of complex interacting factors. Many different sources and transmission pathways contribute to the ever-growing burden of AMR in our clinical settings. The lack of data on these mechanisms and the relative importance of different factors causing the emergence and spread of AMR hampers our global efforts to effectively manage the risks. Importantly, we have little quantitative knowledge on the relative contributions of these sources and are likely to be targeting our interventions suboptimally as a result. Here we propose a systems mapping approach to address the urgent need for reliable and timely data in order to strengthen the response to AMR.
Boyd S, moore LSP, Rawson TM, et al., 2017, Combination therapy for carbapenemase-producing Entero-bacteriaceae: INCREMENT-al effect on resistance remains unclear, The Lancet Infectious Diseases, Vol: 17, Pages: 899-900, ISSN: 1473-3099
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