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  • Journal article
    Charani E, Holmes A, Bonaconsa C, Mbamalu O, Mendelson M, Surendran S, Singh S, Nampoothiri V, Boutall A, Tarrant C, Dhar P, Pennel T, Leather A, Hampton Met al., 2021,

    Investigating infection management and antimicrobial stewardship in surgery: a qualitative study from India and South Africa

    , Clinical Microbiology and Infection, Vol: 27, Pages: 1455-1464, ISSN: 1198-743X

    Objectives To investigate the drivers for infection management and antimicrobial stewardship (AMS) across high infection risk surgical pathways. Methods An qualitative study, ethnographic observation of clinical practices, patient case studies, and face-to-face interviews with healthcare professionals (HCP) and patients was conducted across cardiovascular and thoracic and gastrointestinal surgical pathways in South Africa (SA) and India. Aided by Nvivo 11 software, data were coded and analysed until saturation was reached. The multiple modes of enquiry enabled cross-validation and triangulation of findings.Results Between July 2018–August 2019 data were gathered from 190 hours of non-participant observations (138 India, 72 SA); interviews with HCPs (44 India, 61 SA); patients (6 India, 8 SA), and, case studies (4 India, 2 SA). Across the surgical pathway, multiple barriers impede effective infection management and AMS. The existing, implicit roles of HCPs (including nurses, and senior surgeons) are overlooked as interventions target junior doctors, bypassing the opportunity for integrating infection-related care across the surgical team. Critically, the ownership of decisions remains with the operating surgeons and entrenched hierarchies restrict the inclusion of other HCPs in decision-making. The structural foundations to enable staff to change their behaviours and participate in infection-related surgical care is lacking.ConclusionsIdentifying the implicit existing HCPs roles in infection management is critical and will facilitate the development of effective and transparent processes across the surgical team for optimised care. Applying a framework approach that includes nurse leadership, empowering pharmacists and engaging surgical leads is essential for integrated AMS and infection-related care. Keywords: antibiotic prescribing, infection control, ethnography, low- and middle-income country, surgery

  • Journal article
    Bonaconsa C, Mbamalu O, Mendelson M, Boutall A, Warden C, Rayamajhi S, Pennel T, Hampton M, Joubert I, Tarrant C, Holmes A, Charani Eet al., 2021,

    Visual mapping of team dynamics and communication patterns on surgical ward rounds: an ethnographic study

    , BMJ Quality & Safety, Vol: 30, Pages: 812-824, ISSN: 2044-5415

    Background: Team dynamics influence infection prevention and management practices and implementation of antibiotic stewardship (AS). Using an innovative visual mapping approach, alongside traditional qualitative methods, we aimed to study team dynamics and flow of communication (who gets to speak, and whose voice is heard) during surgical ward rounds, and how team dynamics and communication patterns may shape decision-making in relation to infection management and AS.Materials/methods: Between May and November 2019, data were gathered through direct observations of ward rounds and face-to-face interviews with ward round participants in selected surgical specialties at a tertiary hospital in South Africa. Using a visual mapping method – sociograms – content and flow of communication and the social links between individual participants were plotted. Field notes from observations and interview transcripts were analysed using a grounded theory approach.Results: Data were gathered from 60 hours of ward round observations, including 1024 individual patient discussions; 60 sociograms, interviews with healthcare professionals (60) and patients (7). The nature of discussions about AS and IPC on ward rounds vary across specialties and are affected by the content and structure of the clinical update provided, the consultant’s leadership and interaction style, and competing priorities at the bedside. Registrars act as gatekeepers, initiating antibiotic discussions; consultants are key decision-makers. Other team members have limited input in ward round conversations, despite having recognised roles in AS and IPC. Hierarchies in teams manifest themselves on ward rounds in where staff position themselves, influencing their contribution to care. Varied leadership styles affect ward-round dynamics, in particular, whether nurses and patients are actively engaged in key decisions on infection management and antibiotic therapy, and whether actions are assigned to i

  • Journal article
    Collin SM, Groves N, O' Sullivan C, Jauneikaite E, Patel D, CUnney R, Meehan M, Reynolds A, Smith A, Lindsay D, Doherty L, Davies E, Chalker V, Lamb P, Afshar B, Balasegaram S, Coelho J, Ready D, Brown CS, Efstratiou A, Le Doare K, Sriskandan S, Heath PT, Lamagni Tet al., 2021,

    Uncovering infant group B streptococcal (GBS) disease clusters in the UK and Ireland through genomic analysis: a population-based epidemiological study

    , Clinical Infectious Diseases, Vol: 72, Pages: e296-e302, ISSN: 1058-4838

    BackgroundThe true frequency of hospital outbreaks of invasive group B streptococcal (iGBS; Streptococcus agalactiae) disease in infants is unknown. We used whole genome sequencing (WGS) of iGBS isolates collected during a period of enhanced surveillance of infant iGBS disease in the UK and Ireland to determine the number of clustered cases.MethodsPotentially linked iGBS cases from infants with early (<7 days of life) or late-onset (7–89 days) disease were identified from WGS data (HiSeq 2500 platform, Illumina) from clinical sterile site isolates collected between 04/2014 and 04/2015. We assessed time and place of cases to determine a single-nucleotide polymorphism (SNP) difference threshold for clustered cases. Case details were augmented through linkage to national hospital admission data and hospital record review by local microbiologists.ResultsAnalysis of sequences indicated a cutoff of ≤5 SNP differences to define iGBS clusters. Among 410 infant iGBS isolates, we identified 7 clusters (4 genetically identical pairs with 0 SNP differences, 1 pair with 3 SNP differences, 1 cluster of 4 cases with ≤1 SNP differences) of which 4 clusters were uncovered for the first time. The clusters comprised 16 cases, of which 15 were late-onset (of 192 late-onset cases with sequenced isolates) and 1 an early-onset index case. Serial intervals between cases ranged from 0 to 59 (median 12) days.ConclusionsApproximately 1 in 12 late-onset infant iGBS cases were part of a hospital cluster. Over half of the clusters were previously undetected, emphasizing the importance of routine submission of iGBS isolates to reference laboratories for cluster identification and genomic confirmation.

  • Journal article
    Arkell P, Mahboobani S, Wilson R, Fatania N, Coleman M, Borman AM, Johnson EM, Armstrong-James DPH, Abdolrasouli Aet al., 2021,

    Bronchoalveolar lavage fluid IMMY Sona Aspergillus lateral-flow assay for the diagnosis of invasive pulmonary aspergillosis: a prospective, real life evaluation

    , MEDICAL MYCOLOGY, Vol: 59, Pages: 404-408, ISSN: 1369-3786
  • Journal article
    Pallett SJC, Denny S, Patel A, Charani E, Mughal N, Stebbing J, Davies G, Moore Let al., 2021,

    Point-of-care SARS-CoV-2 serological assays for enhanced case finding in a UK inpatient population.

    , Scientific Reports, Vol: 11, Pages: 1-8, ISSN: 2045-2322

    Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic. Case identification is currently made by real-time polymerase chain reaction (PCR) during the acute phase and largely restricted to healthcare laboratories. Serological assays are emerging but independent validation is urgently required to assess their utility. We evaluated five different point-of-care (POC) SARS-CoV-2 antibody test kits against PCR, finding concordance across the assays (n=15). We subsequently tested 200 patients using the OrientGene COVID-19 IgG/IgM Rapid Test Cassette and find a sensitivity of 74% in the early infection period (day 5-9 post symptom onset), with 100% sensitivity not seen until day 13, demonstrating inferiority to PCR testing in the infectious period. Negative rate was 96%, but in validating the serological tests uncovered potential false-negatives from PCR testing late-presenting cases. A positive predictive value (PPV) of 37% in the general population precludes any use for general screening. Where a case definition is applied however, the PPV is substantially improved (95·4%), supporting use of serology testing in carefully targeted, high-risk populations. Larger studies in specific patient cohorts, including those with mild infection are urgently required to inform on the applicability of POC serological assays to help control the spread of SARS-CoV-2 and improve case finding of patients that may experience late complications.

  • 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., 2021,

    Handheld point-of-care system for rapid detection of SARS-CoV-2 extracted RNA in under 20 min

    , ACS Central Science, Vol: 7, Pages: 307-317, ISSN: 2374-7943

    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 (<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 extracted RNA from 183 clinical samples including 127 positive samples (screened by the CDC RT-qPCR assay). Results showed 91% 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 = 52), showing average detection times of 12.68 ± 2.56 min for positive samples (n = 34), demonstrating a comparable performance to a benchtop commercial instrument. Paired with a smartphone for results visualization and geolocalization, this portable diagnostic platform with secure cloud connectivity will enable real-time case identification and epidemiological surveillance.

  • Journal article
    Singh S, Charani E, Devi S, Sharma A, Edathadathil F, Kumar A, Warrier A, Shareek PS, Jaykrishnan A, Ellangovan Ket al., 2021,

    A road-map for addressing antimicrobial resistance in low- and middle-income countries: lessons learnt from the public private participation and co-designed antimicrobial stewardship programme in the State of Kerala, India

    , Antimicrobial Resistance and Infection Control, Vol: 10, ISSN: 2047-2994

    BackgroundThe global concern over antimicrobial resistance (AMR) is gathering pace. Low- and middle-income countries (LMICs) are at the epicentre of this growing public health threat and governmental and healthcare organizations are at different stages of implementing action plans to tackle AMR. The South Indian state of Kerala was one of the first in India to implement strategies and prioritize activities to address this public health threat.StrategiesThrough a committed and collaborative effort from all healthcare related disciplines and its professional societies from both public and private sector, the Kerala Public Private Partnership (PPP) has been able to deliver a state-wide strategy to tackle AMR A multilevel strategic leadership model and a multilevel implementation approach that included developing state-wide antibiotic clinical guidelines, a revision of post-graduate and undergraduate medical curriculum, and a training program covering all general practitioners within the state the PPP proved to be a successful model for ensuring state-wide implementation of an AMR action plan. Collaborative work of multi-professional groups ensured co-design and development of disease based clinical treatment guidelines and state-wide infection prevention policy. Knowledge exchange though international and national platforms in the form of workshops for sharing of best practices is critical to success. Capacity building at both public and private institutions included addressing practical and local solutions to the barriers e.g. good antibiotic prescription practices from primary to tertiary care facility and infection prevention at all levels.ConclusionThrough 7 years of stakeholder engagement, lobbying with government, and driving change through co-development and implementation, the PPP successfully delivered an antimicrobial stewardship plan across the state. The roadmap for the implementation of the Kerala PPP strategic AMR plan can provide learning for other state

  • Journal article
    Boonyasiri A, Jauneikaite E, Brinkac LM, Greco C, Lerdlamyong K, Tangkoskul T, Nguyen K, Thamlikitkul V, Fouts DEet al., 2021,

    Genomic and clinical characterisation of multidrug-resistant carbapenemase-producing ST231 and ST16 Klebsiella pneumoniae isolates colonising patients at Siriraj hospital, Bangkok, Thailand from 2015 to 2017.

    , BMC Infectious Diseases, Vol: 21, Pages: 1-11, ISSN: 1471-2334

    BACKGROUND: Infections caused by carbapenemase-producing Enterobacteriaceae (CPE) have continually grown as a global public health threat, with significant mortality rates observed across the world. We examined the clinical data from patients with CPE infections and their outcomes, concentrating on Klebsiella pneumoniae isolates. We analysed the clinical information, performed antimicrobial susceptibility testing, and conducted molecular epidemiological and genomic analyses on the isolates to identify patterns in the data. METHODS: The clinical characteristics of 33 hospitalised patients with confirmed CPE, including patient-related factors associated with the development of CPE infections, were examined. Patients were divided according to whether they were "colonised" or "infected" with CPE and by the timing and frequency of their rectal swab collections, from which 45 swabs were randomly selected for analysis. CPE isolates were purified, and antimicrobial susceptibility tests performed. Whole genome sequences of these isolates were determined and analysed to compute bacterial multilocus sequence types and plasmid replicon types, infer phylogenetic relationships, and identify antimicrobial resistance and virulence genes. RESULTS: Altogether, 88.9% (40/45) of the CPE isolates were K. pneumoniae. The most abundant carbapenemase gene family in the K. pneumoniae isolates (33/39) was blaOXA-232, with blaNDM-1 additionally identified in 19 of them. All CPE isolates carrying either blaOXA-232 or blaNDM-1 were resistant to meropenem, but only 40 from 45 were susceptible to colistin. Among the CPE-infected patients (n = 18) and CPE-colonised patients who developed CPE infections during the study (n = 3), all but one received standard colistin-based combination therapy. Phylogenetic analysis revealed the polyclonal spread of carbapenemase-producing K. pneumoniae (CPKP) within the patient population, with the following two major

  • Journal article
    Nampoothiri V, Sudhir AS, Joseph MV, Mohamed Z, Menon V, Charani E, Singh Set al., 2021,

    Mapping the Implementation of a Clinical Pharmacist-Driven Antimicrobial Stewardship Programme at a Tertiary Care Centre in South India

    , ANTIBIOTICS-BASEL, Vol: 10, ISSN: 2079-6382
  • Journal article
    Borek AJ, Campbell A, Dent E, Butler CC, Holmes A, Moore M, Walker AS, McLeod M, Tonkin-Crine Set al., 2021,

    Implementing interventions to reduce antibiotic use: a qualitative study in high-prescribing practices

    , BMC Family Practice, Vol: 22, ISSN: 1471-2296

    BackgroundTrials have shown that delayed antibiotic prescriptions (DPs) and point-of-care C-Reactive Protein testing (POC-CRPT) are effective in reducing antibiotic use in general practice, but these were not typically implemented in high-prescribing practices. We aimed to explore views of professionals from high-prescribing practices about uptake and implementation of DPs and POC-CRPT to reduce antibiotic use.MethodsThis was a qualitative focus group study in English general practices. The highest antibiotic prescribing practices in the West Midlands were invited to participate. Clinical and non-clinical professionals attended focus groups co-facilitated by two researchers. Focus groups were audio-recorded, transcribed verbatim and analysed thematically.ResultsNine practices (50 professionals) participated. Four main themes were identified. Compatibility of strategies with clinical roles and experience – participants viewed the strategies as having limited value as ‘clinical tools’, perceiving them as useful only in ‘rare’ instances of clinical uncertainty and/or for those less experienced. Strategies as ‘social tools’ – participants perceived the strategies as helpful for negotiating treatment decisions and educating patients, particularly those expecting antibiotics. Ambiguities – participants perceived ambiguities around when they should be used, and about their impact on antibiotic use. Influence of context – various other situational and practical issues were raised with implementing the strategies.ConclusionsHigh-prescribing practices do not view DPs and POC-CRPT as sufficiently useful ‘clinical tools’ in a way which corresponds to the current policy approach advocating their use to reduce clinical uncertainty and improve antimicrobial stewardship. Instead, policy attention should focus on how these strategies may instead be used as ‘social tools’ to reduce unnecessary antibio

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