Improved diagnostics of infectious diseases in emergency departments: a protocol of a multifaceted multicentre diagnostic study

Helene Skjøt-Arkil, Anne Heltborg, Morten Hjarnø Lorentzen, Mariana Bichuette Cartuliares, Mathias Amdi Hertz, Ole Graumann, Flemming S Rosenvinge, Eva Rabing Brix Petersen, Claus Østergaard, Christian B Laursen, Thor Aage Skovsted, Stefan Posth, Ming Chen, Christian Backer Mogensen, Helene Skjøt-Arkil, Anne Heltborg, Morten Hjarnø Lorentzen, Mariana Bichuette Cartuliares, Mathias Amdi Hertz, Ole Graumann, Flemming S Rosenvinge, Eva Rabing Brix Petersen, Claus Østergaard, Christian B Laursen, Thor Aage Skovsted, Stefan Posth, Ming Chen, Christian Backer Mogensen

Abstract

Background: The major obstacle in prescribing an appropriate and targeted antibiotic treatment is insufficient knowledge concerning whether the patient has a bacterial infection, where the focus of infection is and which bacteria are the agents of the infection. A prerequisite for the appropriate use of antibiotics is timely access to accurate diagnostics such as point-of-care (POC) testing.The study aims to evaluate diagnostic tools and working methods that support a prompt and accurate diagnosis of hospitalised patients suspected of an acute infection. We will focus on the most common acute infections: community-acquired pneumonia (CAP) and acute pyelonephritis (APN). The objectives are to investigate (1) patient characteristics and treatment trajectory of the different acute infections, (2) diagnostic and prognostic accuracy of infection markers, (3) diagnostic accuracy of POC urine flow cytometry on diagnosing and excluding bacteriuria, (4) how effective the addition of POC analysis of sputum to the diagnostic set-up for CAP is on antibiotic prescriptions, (5) diagnostic accuracy of POC ultrasound and ultralow dose (ULD) computerized tomography (CT) on diagnosing CAP, (6) diagnostic accuracy of specialist ultrasound on diagnosing APN, (7) diagnostic accuracy of POC ultrasound in diagnosing hydronephrosis in patients suspected of APN.

Methods and analysis: It is a multifaceted multicentre diagnostic study, including 1000 adults admitted with suspicion of an acute infection. Participants will, within the first 24 hours of admission, undergo additional diagnostic tests including infection markers, POC urine flow cytometry, POC analysis of sputum, POC and specialist ultrasound, and ULDCT. The primary reference standard is an assigned diagnosis determined by a panel of experts.

Ethics, dissemination and registration: Approved by Regional Committees on Health Research Ethics for Southern Denmark, Danish Data Protection Agency and clinicaltrials.gov. Results will be presented in peer-reviewed journals, and positive, negative and inconclusive results will be published.

Trial registration numbers: NCT04661085, NCT04681963, NCT04667195, NCT04652167, NCT04686318, NCT04686292, NCT04651712, NCT04645030, NCT04651244.

Keywords: accident & emergency medicine; computed tomography; diagnostic microbiology; diagnostic radiology; microbiology; ultrasound.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Design of patient flow and diagnostic tracks. APN, acute pyelonephritis; CAP, community-acquired pneumonia; ED, emergency department: HRCT, high-resolution CT; POC, point-of-care; UFC, urine flow cytometry; ULDCT, ultralow dose CT; US, ultrasound scanning.

References

    1. WHO . Antimicrobial resistance - Global report and surveillance. France: World Health Organization, 2014.
    1. Bager FE-I J, Larsen AR, Sönksen UW. DANMAP 2018 - Use of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from food animals, food and humans in Denmark, 2018.
    1. Skjøt-Arkil H, Mogensen CB, Lassen AT, et al. . Carrier prevalence and risk factors for colonisation of multiresistant bacteria in Danish emergency departments: a cross-sectional survey. BMJ Open 2019;9:e029000. 10.1136/bmjopen-2019-029000
    1. Sundhedsstyrelsen . Vejledning Om ordination AF antibiotika. Copenhagen: Danish Health Organisaztion, 2012.
    1. Sundhedsstyrelsen . Vejledning Om forebyggelse AF spredning AF MRSA, 2016.
    1. Sundhedsstyrelsen . Vejledning OG forebyggelse AF Om spredning AF CPO, 2018.
    1. Ældreministeriet S-o . National handlingsplan for antibiotika til mennesker - tre målbare mål for en reduktion af antibiotikaforbruget frem mod 2020, 2017.
    1. Hellesøe AM, Anhøj CB.;, Jensen J.;. LKT Antibiotika afslutnings- OG evalueringsrapport, 2019.
    1. Cartuliares MB, Sundal LM, Gustavsson S, et al. . Limited value of sputum culture to guide antibiotic treatment in a Danish emergency department. Dan Med J 2020;67:A11190641.
    1. Funk DJ, Kumar A. Antimicrobial therapy for life-threatening infections: speed is life. Crit Care Clin 2011;27:53–76. 10.1016/j.ccc.2010.09.008
    1. World Health Organization . The top 10 causes of death, 2018. Available: [Accessed July 2019].
    1. Kennedy M, Joyce N, Howell MD, et al. . Identifying infected emergency department patients admitted to the hospital ward at risk of clinical deterioration and intensive care unit transfer. Acad Emerg Med 2010;17:1080–5. 10.1111/j.1553-2712.2010.00872.x
    1. Chandra A, Nicks B, Maniago E, et al. . A multicenter analysis of the ED diagnosis of pneumonia. Am J Emerg Med 2010;28:862–5. 10.1016/j.ajem.2009.04.014
    1. Reed WW, Byrd GS, Gates RH, et al. . Sputum gram's stain in community-acquired pneumococcal pneumonia. A meta-analysis. West J Med 1996;165:197–204.
    1. Schuetz P, Christ-Crain M, Müller B. Procalcitonin and other biomarkers to improve assessment and antibiotic stewardship in infections--hope for hype? Swiss Med Wkly 2009;139:318–26.
    1. Savvateeva EN, Rubina AY, Gryadunov DA. Biomarkers of community-acquired pneumonia: a key to disease diagnosis and management. Biomed Res Int 2019;2019:1–20. 10.1155/2019/1701276
    1. Hey J, Thompson-Leduc P, Kirson NY, et al. . Procalcitonin guidance in patients with lower respiratory tract infections: a systematic review and meta-analysis. Clin Chem Lab Med 2018;56:1200–9. 10.1515/cclm-2018-0126
    1. Self WH, Balk RA, Grijalva CG, et al. . Procalcitonin as a marker of etiology in adults hospitalized with community-acquired pneumonia. Clin Infect Dis 2017;65:183–90. 10.1093/cid/cix317
    1. Hamie L, Daoud G, Nemer G, et al. . SuPAR, an emerging biomarker in kidney and inflammatory diseases. Postgrad Med J 2018;94:517–24. 10.1136/postgradmedj-2018-135839
    1. Masajtis-Zagajewska A, Nowicki M. New markers of urinary tract infection. Clin Chim Acta 2017;471:286–91. 10.1016/j.cca.2017.06.003
    1. Caterino JM, Leininger R, Kline DM, et al. . Accuracy of current diagnostic criteria for acute bacterial infection in older adults in the emergency department. J Am Geriatr Soc 2017;65:1802–9. 10.1111/jgs.14912
    1. Bourcier J-E, Paquet J, Seinger M, et al. . Performance comparison of lung ultrasound and chest X-ray for the diagnosis of pneumonia in the ED. Am J Emerg Med 2014;32:115–8. 10.1016/j.ajem.2013.10.003
    1. Orso D, Guglielmo N, Copetti R. Lung ultrasound in diagnosing pneumonia in the emergency department: a systematic review and meta-analysis. Eur J Emerg Med 2018;25:312–21. 10.1097/MEJ.0000000000000517
    1. Claeys KC, Blanco N, Morgan DJ, et al. . Advances and challenges in the diagnosis and treatment of urinary tract infections: the need for diagnostic stewardship. Curr Infect Dis Rep 2019;21:11. 10.1007/s11908-019-0668-7
    1. Shallcross L, Gaskell K, Fox-Lewis A, et al. . Mismatch between suspected pyelonephritis and microbiological diagnosis: a cohort study from a UK teaching hospital. J Hosp Infect 2018;98:219–22. 10.1016/j.jhin.2017.09.029
    1. Quaia E, Correas JM, Mehta M, et al. . Gray scale ultrasound, color Doppler ultrasound, and contrast-enhanced ultrasound in renal parenchymal diseases. Ultrasound Q 2018;34:250–67. 10.1097/RUQ.0000000000000383
    1. Mitterberger M, Pinggera GM, Colleselli D, et al. . Acute pyelonephritis: comparison of diagnosis with computed tomography and contrast-enhanced ultrasonography. BJU Int 2008;101:341–4. 10.1111/j.1464-410X.2007.07280.x
    1. Kazmierski B, Deurdulian C, Tchelepi H, et al. . Applications of contrast-enhanced ultrasound in the kidney. Abdom Radiol 2018;43:880–98. 10.1007/s00261-017-1307-0
    1. Huang H-S, Tsai C-L, Chang J, et al. . Multiplex PCR system for the rapid diagnosis of respiratory virus infection: systematic review and meta-analysis. Clin Microbiol Infect 2018;24:1055–63. 10.1016/j.cmi.2017.11.018
    1. Long B, Koyfman A. The emergency department diagnosis and management of urinary tract infection. Emerg Med Clin North Am 2018;36:685–710. 10.1016/j.emc.2018.06.003
    1. Rowe TA, Juthani-Mehta M. Diagnosis and management of urinary tract infection in older adults. Infect Dis Clin North Am 2014;28:75–89. 10.1016/j.idc.2013.10.004
    1. Institut SS. Urinvejsinfektioner: Blærebetændelse OG nyrebækkenbetændelse Statens serum Institut: Statens Seum Institut, 2017. Available: [Accessed April 2019].
    1. Herráez O, Asencio MA, Carranza R, et al. . Sysmex UF-1000i flow cytometer to screen urinary tract infections: the URISCAM multicentre study. Lett Appl Microbiol 2018;66:175–81. 10.1111/lam.12832
    1. Chan A-W, Tetzlaff JM, Altman DG, et al. . Spirit 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med 2013;158:200–7. 10.7326/0003-4819-158-3-201302050-00583
    1. The region of southern Denmark traw . Den Regionale Antibiotikagruppe. Diagnostik OG behandling AF akutte infektioner på sygehusene I region Syddanmark, 2016.
    1. Skovsted TA, Petersen ERB, Fruekilde M-B, et al. . Validation of suPAR turbidimetric assay on Cobas® (c502 and c702) and comparison to suPAR ELISA. Scand J Clin Lab Invest 2020;80:327–35. 10.1080/00365513.2020.1741674
    1. BioFire . Filmarray pneumonia panel instruction booklet RFIT-ASY0144/145. UT: BioFire SLC, 2018.
    1. Harris PA, Taylor R, Thielke R, et al. . Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009;42:377–81. 10.1016/j.jbi.2008.08.010
    1. Volpicelli G, Elbarbary M, Blaivas M, et al. . International evidence-based recommendations for point-of-care lung ultrasound. Intensive Care Med 2012;38:577–91. 10.1007/s00134-012-2513-4
    1. Laursen CB, Clive A, Hallifax R, et al. . European respiratory Society statement on thoracic ultrasound. Eur Respir J 2021;57:2001519. 10.1183/13993003.01519-2020
    1. Laursen BLG, Davidsen JR, et al. . Basal klinisk ultralydsdiagnostik. Copenhagen: Munksgaard, 2017.
    1. Biosoft . easyROC: a web-tool for ROC curve analysis. Available: [Accessed 03 Jan 2020].
    1. Mody L, Juthani-Mehta M. Urinary tract infections in older women: a clinical review. JAMA 2014;311:844–54. 10.1001/jama.2014.303
    1. GAIL MH, WIEAND S, PIANTADOSI S. Biased estimates of treatment effect in randomized experiments with nonlinear regressions and omitted covariates. Biometrika 1984;71:431–44. 10.1093/biomet/71.3.431
    1. Huda W, Ogden KM, Khorasani MR. Converting dose-length product to effective dose at CT. Radiology 2008;248:995–1003. 10.1148/radiol.2483071964
    1. Sodickson A, Baeyens PF, Andriole KP, et al. . Recurrent CT, cumulative radiation exposure, and associated radiation-induced cancer risks from CT of adults. Radiology 2009;251:175–84. 10.1148/radiol.2511081296
    1. Brenner DJ, Hall EJ. Computed tomography--an increasing source of radiation exposure. N Engl J Med 2007;357:2277–84. 10.1056/NEJMra072149
    1. Mayo-Smith WW, Hara AK, Mahesh M, et al. . How I do it: managing radiation dose in CT. Radiology 2014;273:657–72. 10.1148/radiol.14132328
    1. Chong WK, Papadopoulou V, Dayton PA. Imaging with ultrasound contrast agents: current status and future. Abdom Radiol 2018;43:762–72. 10.1007/s00261-018-1516-1
    1. Cohen JF, Korevaar DA, Altman DG, et al. . Stard 2015 guidelines for reporting diagnostic accuracy studies: explanation and elaboration. BMJ Open 2016;6:e012799. 10.1136/bmjopen-2016-012799
    1. Vandenbroucke JP, von Elm E, Altman DG, et al. . Strengthening the reporting of observational studies in epidemiology (STROBE): explanation and elaboration. PLoS Med 2007;4:e297. 10.1371/journal.pmed.0040297
    1. Moher D, Hopewell S, Schulz KF, et al. . Consort 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. BMJ 2010;340:c869. 10.1136/bmj.c869

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