{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T13:09:18Z","timestamp":1789996158228,"version":"4.0.1"},"update-to":[{"DOI":"10.12688\/wellcomeopenres.15681.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T00:00:00Z","timestamp":1590969600000}}],"reference-count":26,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T00:00:00Z","timestamp":1590969600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["215867"],"award-info":[{"award-number":["215867"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"\n Background<\/ns4:bold>\n : Antimicrobial resistance (AMR) \/ drug resistant infections (DRIs) are a major global health priority. Surveillance data is critical to inform infection treatment guidelines, monitor trends, and to assess interventions. However, most existing AMR \/ DRI surveillance systems are passive and pathogen-based with many potential biases. Addition of clinical and patient outcome data would provide considerable added value to pathogen-based surveillance.\n <\/ns4:p>\n \n Methods<\/ns4:bold>\n : The aim of the ACORN project is to develop an efficient clinically-oriented AMR surveillance system, implemented alongside routine clinical care in hospitals in low- and middle-income country settings. In an initial pilot phase, clinical and microbiology data will be collected from patients presenting with clinically suspected meningitis, pneumonia, or sepsis. Community-acquired infections will be identified by daily review of new admissions, and hospital-acquired infections will be enrolled during weekly point prevalence surveys, on surveillance wards. Clinical variables will be collected at enrolment, hospital discharge, and at day 28 post-enrolment using an electronic questionnaire on a mobile device. These data will be merged with laboratory data onsite using a flexible automated computer script. Specific target pathogens will be\n Streptococcus pneumoniae, Staphylococcus aureus, Salmonella<\/ns4:italic>\n spp\n ., Klebsiella pneumoniae, Escherichia coli,<\/ns4:italic>\n and\n Acinetobacter baumannii<\/ns4:italic>\n . A bespoke browser-based app will provide sites with fully interactive data visualisation, analysis, and reporting tools.\n <\/ns4:p>\n \n Discussion<\/ns4:bold>\n : ACORN will generate data on the burden of DRI which can be used to inform local treatment guidelines \/ national policy and serve as indicators to measure the impact of interventions. Following development, testing and iteration of the surveillance tools during an initial six-month pilot phase, a wider rollout is planned.\n <\/ns4:p>","DOI":"10.12688\/wellcomeopenres.15681.2","type":"journal-article","created":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T11:40:05Z","timestamp":1591011605000},"page":"13","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["ACORN (A Clinically-Oriented Antimicrobial Resistance Surveillance Network): a pilot protocol for case based antimicrobial resistance surveillance"],"prefix":"10.12688","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1013-7815","authenticated-orcid":false,"given":"Paul","family":"Turner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7620-4822","authenticated-orcid":false,"given":"Elizabeth A.","family":"Ashley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2971-9110","authenticated-orcid":false,"given":"Olivier J.","family":"Celhay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anousone","family":"Douangnouvong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5007-7896","authenticated-orcid":false,"given":"Raph L.","family":"Hamers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clare L.","family":"Ling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0237-1070","authenticated-orcid":false,"given":"Yoel","family":"Lubell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thyl","family":"Miliya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8599-737X","authenticated-orcid":false,"given":"Tamalee","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chansovannara","family":"Soputhy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pham","family":"Ngoc Thach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manivanh","family":"Vongsouvath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2267-9347","authenticated-orcid":false,"given":"Naomi","family":"Waithira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prapass","family":"Wannapinij","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9807-1821","authenticated-orcid":false,"given":"H. Rogier","family":"van Doorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2020,6,1]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"1737-49","DOI":"10.1093\/jac\/dky026","article-title":"An inventory of supranational antimicrobial resistance surveillance networks involving low- and middle-income countries since 2000.","volume":"73","author":"E Ashley","year":"2018","journal-title":"J Antimicrob Chemother."},{"key":"ref-2","article-title":"Diagnostic stewardship: A guide to implementation in antimicrobial resistance surveillance sites (WHO\/DGO\/AMR\/2016.3)","year":"2016"},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"1665-73","DOI":"10.1017\/S0950268809990100","article-title":"Surveillance for antimicrobial resistant organisms: potential sources and magnitude of bias.","volume":"137","author":"O Rempel","year":"2009","journal-title":"Epidemiol 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approved, 1 approved with reservations].","volume":"2","author":"A Seale","year":"2017","journal-title":"Wellcome Open Res."},{"key":"ref-8","article-title":"ACORN Laboratory Assessment SOP \/ Form.","author":"P Turner","year":"2020","journal-title":"figshare."},{"key":"ref-9","article-title":"ACORN Site Preparation SOP \/ Form.","author":"P Turner","year":"2020","journal-title":"figshare."},{"key":"ref-10","article-title":"ACORN Clinician KAP Survey \/ Form.","author":"P Turner","year":"2020","journal-title":"figshare."},{"key":"ref-11","article-title":"ACORN Diagnostic Stewardship SOP \/ Form.","author":"P Turner","year":"2020","journal-title":"figshare."},{"key":"ref-12","article-title":"ACORN Community Acquired Infection Enrolment SOP.","author":"P Turner","year":"2020","journal-title":"figshare."},{"key":"ref-13","article-title":"ACORN Hospital Acquired Infection Point Prevalence Survey SOP.","author":"P Turner","year":"2020","journal-title":"figshare."},{"key":"ref-14","article-title":"ACORN Participant Information Sheet.","author":"P Turner","year":"2020","journal-title":"figshare."},{"key":"ref-15","article-title":"ACORN Patient Follow-up SOP.","author":"P Turner","year":"2020","journal-title":"figshare."},{"key":"ref-16","article-title":"ACORN ODK Data Entry SOP \/ Form.","author":"P Turner","year":"2020","journal-title":"figshare."},{"key":"ref-17","article-title":"AMR Surveillance in low- and middle-income settings - A roadmap for participation in the Global Antimicrobial Surveillance System (GLASS)","year":"2016"},{"key":"ref-18","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1186\/s13063-018-2587-6","article-title":"Continuous versus intermittent endotracheal cuff pressure control for the prevention of ventilator-associated respiratory infections in Vietnam: study protocol for a randomised controlled trial.","volume":"19","author":"V 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Ryu","year":"2019","journal-title":"JAC-Antimicrobial Resistance."}],"container-title":["Wellcome Open Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-13\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-13\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-13\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T23:15:15Z","timestamp":1718752515000},"score":1,"resource":{"primary":{"URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-13\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,1]]},"references-count":26,"URL":"https:\/\/doi.org\/10.12688\/wellcomeopenres.15681.2","relation":{"has-version":[{"id-type":"doi","id":"10.12688\/wellcomeopenres.15681.1","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.21956\/wellcomeopenres.17566.r38904","asserted-by":"subject"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.17566.r38906","asserted-by":"subject"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.17566.r38906","asserted-by":"object"},{"id-type":"doi","id":"10.21956\/wellcomeopenres.17566.r38904","asserted-by":"object"}]},"ISSN":["2398-502X"],"issn-type":[{"value":"2398-502X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,1]]},"assertion":[{"value":"Indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-13\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/wellcomeopenres.17566.r38906, Rebecca Lester, Liverpool School of Tropical Medicine, Liverpool, 02 Jun 2020, version 2, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-13\/v2#referee-response-38906","order":0,"name":"referee-response-38906","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.17566.r38904, Maya Nadimpalli, Tufts University, Medford, MA, 02 Jun 2020, version 2, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-13\/v2#referee-response-38904","order":1,"name":"referee-response-38904","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.17186.r38141, Mercy Jemima Newman, Department of Medical Microbiology, University of Ghana, Accra, 20 May 2020, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-13\/v1#referee-response-38141","order":2,"name":"referee-response-38141","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"Paul Turner<\/b>; \nPosted: 26 May 2020<\/i>; \nResponses to reviewer comments: Wellcome Open Research 5-13 V1<\/b>We thank all four reviewers for their extremely helpful and constructive comments. These are all of considerable value as ACORN is iterated prior to wider roll out. Our responses are included as bullet points below.\nReviewer 3<\/b>Summary of the study Shows the importance of diagnostic microbiology for the treatment of systemic infections. Burden of drug resistant serious infections in specific hospitals. Causes and resistance of organisms of HAI and community infections. It will expand on the WHO GLASS and enable classification of infectious syndromes, outcome and associated costs. Surveillance training of hospital personnel. Post-discharge information will be collected e.g. health status and death of patients. Case definitions will be well defined at the end of the study. Peer Review Report Rational for the study - this is clearly described. Study design - this is appropriate for the research. Sufficient detail for the research has been provided. Datasets are adequate   We thank the reviewer for these positive comments.","URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-13\/v2#referee-comment-4186","order":3,"name":"referee-comment-4186","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.17186.r38653, Andrew Whitelaw, Division of Medical Microbiology, Faculty of Medicine and Health Sciences, NHLS, Tygerberg Hospital, Stellenbosch University, Tygerberg, 21 May 2020, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-13\/v1#referee-response-38653","order":4,"name":"referee-response-38653","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"Paul Turner<\/b>; \nPosted: 26 May 2020<\/i>; \nResponses to reviewer comments: Wellcome Open Research 5-13 V1<\/b>We thank all four reviewers for their extremely helpful and constructive comments. These are all of considerable value as ACORN is iterated prior to wider roll out. Our responses are included as bullet points below.\nReviewer 4<\/b>Thanks for the opportunity to review this protocol. The protocol describes an "enhanced surveillance" system focusing on antimicrobial resistance, bringing together patient level clinical and laboratory data. The intention is to generate AMR-data that is more clinically relevant, and less subject to bias. Overall the design is appropriate and is likely to result in better quality AMR data than is currently achieved using lab-based routine data (the default position in many settings). It will also hopefully provide information that can be used to implement similar systems elsewhere We thank the reviewer for these positive comments. There are a few suggestions\/criticisms, but these are relatively minor, and some may not be practical.Page 4: The Surveillance design focuses on a set number of pathogens. It may help to clarify why these were chosen. What happens if a patient is infected with one of the other pathogens - if I understand correctly, they would still be included (or their clinical data will be included), but the organism data would not be part of the dashboard. I think this should be clarified. The organisms selected as the blood culture relevant subset of the WHO GLASS organism list. This detail has been added to the "surveillance design" section of the manuscript. These will form the basis of the reporting dashboard \/ downloadable data summaries. However, it is possible to summarise data regarding infections due to other organisms using the dashboard (but not for now possible to download this as a word document). It is fully anticipated that additional organisms may be added to the core surveillance list as time passes (for example \nEnterococcus <\/i>spp and \nPseudomonas aeruginosa<\/i>). This has been clarified by adding "Whilst the surveillance is focussed on a set of key pathogens, it is recognised that other bacterial species will be cultured from surveillance participant specimens. These species will not be included in formal analyses, but the organism and antimicrobial susceptibility data will be summarised on the interactive dashboard." Page 4: Recruitment: the protocol states that standardised clinical case definitions will be used for training, but will not be required for enrollment during the pilot phase. I think this should be clarified. Why are case definitions not required; and is this specific to the pilot study (i.e. will case definitions be required subsequently)? The discussion makes reference to "pragmatic definitions" being used; and that the issue of case definitions will be reviewed at the end of the pilot phase. The challenge of case definitions is well understood. I am not suggesting that standardised case definitions have to or even can be used for the pilot, but I think the question of what criteria will be used for enrollment needs to be clearer. Linked to this, the definitions in SOP 6 are not clearly laid out (at least to my mind) as case definitions. They come across as clinical criteria that can be used as a guide to suggest pneumonia\/sepsis\/meningitis. We are grateful for this comment, which highlights the most challenging aspect of this project. We agree that the case definitions are worded and formatted with clinical guidance in mind and this was our preferred route for enrolment during the pilot, i.e. that these "definitions" would be used at site training to reinforce clinical diagnosis of the surveillance syndromes and that enrollable cases would thus be "clinically suspected" (but with a greater degree of standardisation). Identification of cases where clinical diagnosis is not well recorded in the medical notes has required the surveillance clinicians to assess patient fit to the case definitions as written. From site feedback, this has been relatively straightforward for pneumonia and meningitis (where the specific criteria required to make the clinical diagnosis are specified in SOP6) but, predictably, has been more of a challenge for sepsis. The manuscript discussion has been updated to: "For this reason, very pragmatic definitions \/ clinical criteria have been employed in the pilot phase of ACORN, with capture of simple severity markers to enable patient stratification within a syndrome. Patients may be enrolled based on clinician diagnosis or, in the absence of clear clinician diagnosis, if they are assessed by the surveillance team as meeting the clinical case criteria for meningitis, pneumonia or sepsis. Widely used clinical definitions are used in diagnostic stewardship activities in an attempt to improve standardisation of clinician diagnosis and specimen collection." Given the current stage of the surveillance (i.e. nearing the end of the pilot), we have not updated the study documents in response to this comment but would very much like to affirm that the point is noted and will be dealt with. On-going discussions at planned pilot investigator and stakeholder meetings will resolve this issue prior to wider rollout. Page 4\/5 - HAI surveillance. This will be done as a point prevalence, weekly. The intention is to capture any patient who may have had an HAI during the previous week. What happens if a patient developed symptoms of an HAI in the preceding week, and either demised, was transferred, or recovered before the surveillance team do the weekly survey? Is there a risk of underestimating HAIs? Conversely, if a patient is included due to a clinically suspected HAI, which is subsequently shown not to be an infection, will this patient be removed from the HAI database? I suspect there is no easy way around this, and illustrates the challenge of any clinical surveillance system. We agree that HAI surveillance is extremely challenging. HAI cases may be missed because of the reasons stated (indeed we note that this has happened during the pilot). Under ideal circumstances those that remain hospitalised but have recovered from their HAI within a week ought to be included, but this will require the surveillance team to maintain diligence in case identification. A comment on this has been added to the discussion: "Another area of uncertainty is around comprehensive capture of HAI cases. The use of point prevalence surveys for identification of HAI is time efficient but may result in underestimation of case numbers due to early death, discharge or recovery. However, this issue is common to all point prevalence surveys and not restricted to ACORN". Those patients included in HAI surveillance but subsequently determined not to infected will be identified as syndrome "rejected" at the hospital outcome data collection point. These cases can then be removed from subsequent analyses. Data management: If I understand, lab data and clinical data will be merged locally to allow for assigning the correct lab data to the correct clinical data. At that stage data will be anonymised and then further analysed. At what time point\/s will this de-identification take place? Is it an ongoing process or only at the end of the pilot? Given that patients are being followed up for 28 days, and thus there are multiple sets of clinical data linked to one patient, and potentially multiple sets of lab data linked to one patient, linking the clinical and lab datasets will need to be an ongoing process, with de-identification only taking place once you are sure that no more data will be forthcoming. This is not explicitly stated - maybe it doesn't need to be. Anonymisation occurs each time clinical and laboratory data are merged which enables the follow-up data to be correctly linked together prior to upload for analysis \/ sharing. The relevant sentence in "data management" has been updated to: " Each time clinical and laboratory data are merged, a unique surveillance ID will be generated for each participant and the participant hospital ID and date of birth will be deleted automatically, rendering a fully de-identified dataset for analysis and further sharing." The study will use a MORU-designed LIMS for labs that have no electronic LIMS. Will this LIMS be accessible to clinical staff at the study sites - it may serve as a positive side effect of the study, and improve access to lab results. Unfortunately, this is not possible at the current stage of development (although the LIMS does include generation of printed and pdf clinician reports). Further development of the LIMS as part of an associated project will address this important gap. The dashboard includes provision of resistance rates for the target pathogens. The example shown has 6 E. coli isolates; and at a facility level the numbers of individual isolates are likely to be low (at least initially). Please be careful of displaying resistance rates for small numbers of organisms as this can be misleading. CLSI recommends at least 30 isolates before showing cumulative resistance\/susceptibility rates. We agree very much with this comment and will add an appropriate disclaimer to the dashboard. The following wording appears already in reports downloaded from the dashboard: "Care should be taken when interpreting rates and AMR profiles where there are small numbers of cases or bacterial isolates: point estimates may be unreliable." Laboratories will use either CLSI or EUCAST criteria. When merging data from different labs, this will create problems when displaying combined susceptibility data - sets of data generated using two different interpretive criteria should not be merged. Thanks for this comment \u2013 we agree it is a problem. The AST criteria used by the laboratory is stored within the merged clinical-lab data file for each site and we will take care not to combine CLSI and EUCAST data. Interpretation of susceptibility may vary depending on site of infection (penicillin for S. pneumoniae). How will this be managed? It would be better to record MIC data and report MICs, rather than categorical interpretation. For now the dashboard displays categorical data interpreted using the epidemiologic (i.e. meningitis) breakpoints for penicillin and \nS. pneumoniae. <\/i>Moving forwards, our intention was to include a second interpretation of the penicillin data using the non-meningitis breakpoints. However, since the final site datafile retains the raw MICs (and zone sizes) alongside categorical interpretations of these, a summary table of MIC values may be a more appropriate way to display these data. Did the authors consider adding an AMS component to the study? One could include data related to whether the prescribed antibiotic for the infection was in line with guidelines; whether de-escalation occurred; whether doses were appropriate etc. (I know this adds to the workload so probably not practical - but worth asking). This is very much something we are considering for future versions of the surveillance protocol. As it stands the documentation of initial treatment will at least permit sites to determine whether empiric guidelines were adhered to. It appears that the surveillance will be done by clinical staff already employed at the hospital. Is this sustainable? Discussions around site-level sustainability are on-going but it will ultimately depend on resources available at the hospital and whether management \/ clinicians feel that the surveillance yields data of sufficient utility to allocate staff time to it. SOP-2 - Laboratory Assessment:On the whole this is quite a comprehensive process. However I think there should be more detail about the AST methods used in the lab. The current form just differentiates manual and automated and asks for free text details. I would suggest tick boxes for disc diffusion, gradient diffusion MIC, broth dilution MIC. It is also complicated by the fact that many labs will use different methods for different organisms. Its not practical to capture all the variations, but identify critical ones - such as penicillin and S. pneumoniae which needs an MIC method. Agreed - we will add this for key bug-drug combinations into the next version of this document. I would suggest a question about whether the lab is accredited to an international standard (such as ISO 15189). This is included in the online document: section 12, ALAF-2: accreditation. I would suggest more information about EQA - maybe review the last set of EQA results; or look for what processes are in place to monitor and resolve faults identified by the EQA process. Agreed - we will add this into the next version of this document.","URL":"https:\/\/wellcomeopenresearch.org\/articles\/5-13\/v2#referee-comment-4187","order":5,"name":"referee-comment-4187","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was supported by the Wellcome Trust [215867; to PT].","order":6,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}