Abstract
Despite the continuous improvement of approaches to antimicrobial therapy and the emergence of new highly effective antibiotics, severe bacterial infections being a significant cause of morbidity and mortality remain a top of mind issue for clinicians. Immediate initiation of the effective antibiotic therapy is an essential component of the successful treatment of serious bacterial infections, and therefore, special attention should be paid to the timely diagnosis. Measurements of biomarkers of inflammation (C-reactive protein, procalcitonin, presepsin, proadrenomedullin) in combination with clinical evaluation are important at first for the diagnosis of bacterial infection, and after that these can help to assess the clinical response to therapy and determine the time-point of antibiotics withdrawal. This review presents the characteristics of the main markers of inflammation, discusses the situations when determination of biomarkers is appropriate, and also provides modern clinical recommendations and algorithms regarding the use of these diagnostic markers in the management of patients with bacterial infections.
N.V. Sklifosovsky Research Institute of Emergency Medicine, Moscow, Russia
N.V. Sklifosovsky Research Institute of Emergency Medicine, Moscow, Russia
Institute of Antimicrobial Chemotherapy, Smolensk, Russia
Institute of Antimicrobial Chemotherapy, Smolensk, Russia
Smolensk State Medical University, Smolensk, Russia
-
1.
World Health Organization. WHO’s first global report on antibiotic resistance reveals serious, worldwide threat to public health. April 30 2014. Available at: www.who.int/mediacentre/news/releases/2014/amr-report/en/. Accessed April 12, 2020.
-
2.
Michael C.A., Dominey-Howes D., Labbate M. The antimicrobial resistance crisis: causes, consequences, and management. Front Public Health. 2014;2:145.
DOI: 10.3389/fpubh.2014.00145
-
3.
Kozlov R.S., Stetsiouk O.U., Andreeva I.V. Current trends in antibiotic resistance of nosocomial infection pathogens in the Russian ICU: what's coming next? Intensivnaja terapija. 2007;4:217-227. Russian.
-
4.
Srinivasan А. Antibiotic stewardship: Why we must, how we can. Cleve Clin J Med. 2017;84(9):673-679.
DOI: 10.3949/ccjm.84gr.17003
-
5.
Stetsiouk O.U., Andreeva I.V. Modern principles of antibacterial therapy of severe and life-threatening bacterial infections. Farmateka. 2008;4:12-17. Russian.
-
6.
Dupuy A.M., Philippart F., Péan Y., Lasocki S., Charles P.E., Chalumeau M., et al. Role of biomarkers in the management of antibiotic therapy: an expert panel review: I – currently available biomarkers for clinical use in acute infections. Ann Intensive Care. 2013;3:22.
DOI: 10.1186/2110-5820-3-22
-
7.
Póvoa P., Salluh J.I.F. Biomarker-guided antibiotic therapy in adult critically ill patients: a critical review. Ann Intensive Care. 2012;2:32.
DOI: 10.1186/2110-5820-2-32
-
8.
Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69(3):89-95.
DOI: 10.1067/mcp.2001.113989
-
9.
Póvoa P., Salluh J.I.F. Use of biomarkers in sepsis: many questions, few answers. Rev Bras Ter Intensiva. 2013;25:1-2.
DOI: 10.1590/s0103-507x2013000100001
-
10.
Heilmann E., Gregoriano C., Schuetz P. Biomarkers of infection: are they useful in the ICU? Semin Respir Crit Care Med. 2019;40(4):465-475.
DOI: 10.1055/s-0039-1696689
-
11.
Nora D., Salluh J., Martin-Loeches I., Póvoa P. Biomarker-guided antibiotic therapy-strengths and limitations. Ann Transl Med. 2017;5(10):208.
DOI: 10.21037/atm.2017.04.04
-
12.
Cho S.Y., Choi J.H. Biomarkers of sepsis. Infect Chemother. 2014;46(1):1-12.
DOI: 10.3947/ic.2014.46.1.1
-
13.
Quenot J.P., Luyt C.E., Roche N., Chalumeau M., Charles P.E., Claessens Y.E., et al. Role of biomarkers in the management of antibiotic therapy: an expert panel review II: clinical use of biomarkers for initiation or discontinuation of antibiotic therapy. Ann Intensive Care. 2013;3:21.
DOI: 10.1186/2110-5820-3-21
-
14.
Memar M.Y., Baghi H.B. Presepsin: a promising biomarker for the detection of bacterial infections. Biomed Pharmacother. 2019;111:649-656.
DOI: 10.1016/j.biopha.2018.12.124
-
15.
Tillet W.S., Francis T. Serological reactions in pneumonia with a non-protein somatic fraction of pneumococcus. J Exp Med. 1930;52(4):561-571.
DOI: 10.1084/jem.52.4.561
-
16.
Markanday A. Acute phase reactants in infections: evidencebased review and a guide for clinicians. Open Forum Infect Dis. 2015;2(3):ofv098.
DOI: 10.1093/ofid/ofv098
-
17.
Ridker P.M. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation. 2003;107(3):363-369.
DOI: 10.1161/01.cir.0000053730.47739.3c
-
18.
Sproston N.R., Ashworth J.J. Role of C-reactive protein at sites of inflammation and infection. Front Immunol. 2018;9:754.
DOI: 10.3389/fimmu.2018.00754
-
19.
Hage F.G., Szalai A.J. C-reactive protein gene polymorphisms, C-reactive protein blood levels, and cardiovascular disease risk. J Am Coll Cardiol. 2007;50(12):1115-1122.
DOI: 10.1016/j.jacc.2007.06.012
-
20.
van der Does Y., Limper M., Schuit S.C., Poley M.J., van Rosmalen J., Ramakers C., et al. Higher diagnostic accuracy and cost-effectiveness using procalcitonin in the treatment of emergency medicine patients with fever (The HiTEMP study): a multicenter randomized study. BMC Emerg Med. 2016;16:17.
DOI: 10.1186/s12873-016-0081-6
-
21.
Harbarth S., Holeckova K., Froidevaux C., Pittet D., Ricou B., Grau G.E., et al. Diagnostic value of procalcitonin, interleukin-6, and interleukin-8 in critically ill patients admitted with suspected sepsis. Am J Respir Crit Care Med. 2001;164(3):396-402.
DOI: 10.1164/ajrccm.164.3.2009052
-
22.
Meisner M. Procalcitonin (PCT) – A new, innovative infection parameter. Biochemical and clinical aspects. Thieme Stuttgart, New York 2000, ISBN: 3-13-105503-0.
-
23.
Schuetz P., Beishuizen A., Broyles M., Ferrer R., Gavazzi G., Gluck E., et al. Procalcitonin (PCT)-guided antibiotic stewardship: an international experts consensus on optimized clinical use. Clin Chem Lab Med. 2019;57(9):1308-1318.
DOI: 10.1515/cclm2018-1181
-
24.
Schuetz P., Wirz Y., Sager R., Christ-Crain M., Stolz D., Tamm M., et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev. 2017; 10:CD007498.
DOI: 10.1002/14651858.CD007498.pub3
-
25.
Schuetz P., Wirz Y., Sager R., Christ-Crain M., Stolz D., Tamm M., et al. Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level metaanalysis. Lancet Infect Dis. 2018;18:95-107.
DOI: 10.1016/S1473-3099(17)30592-3
-
26.
Covington E.W., Roberts M.Z., Dong J. Procalcitonin monitoring as a guide for antimicrobial therapy: a review of current literature. Pharmacotherapy. 2018;38(5):569-581.
DOI: 10.1002/phar.2112
-
27.
Second WHO Model List of Essential In Vitro Diagnostics. [Internet]. 2th List (May 2019). Available at: www.who.int/docs/default-source/nutritionlibrary/complementary-feeding/secondwho-model-list-v8-2019.pdf?sfvrsn=6fe86adf_1.
-
28.
Yaegashi Y., Shirakawa K., Sato N., Suzuki Y., Kojika M., Imai S., et al. Evaluation of a newly identified soluble CD14 subtype as a marker for sepsis. J Infect Chemother. 2005;11(5):234-238.
DOI: 10.1007/s10156-005-0400-4
-
29.
Shozushima T., Takahashi G., Matsumoto N., Kojika M., Okamura Y., Endo S. Usefulness of presepsin (sCD14-ST) measurements as a marker for the diagnosis and severity of sepsis that satisfied diagnostic criteria of systemic inflammatory response syndrome. J Infect Chemother. 2011;17(6):764-769.
DOI: 10.1007/s10156-011-0254-x
-
30.
Velkov V.V. Presepsin – effectiveness of the biological markers for the diagnosis of sepsis and monitoring of systemic infection. Zdorov'e. Medicinskaja jekologija. Nauka. 2016;1(64):4-21. Russian.
-
31.
Zhu Y., Li X., Guo P., Chen Y., Li J., Tao T. The accuracy assessment of presepsin (sCD14-ST) for mortality prediction in adult patients with sepsis and a head-to-head comparison to PCT: a meta-analysis. Ther Clin Risk Manag. 2019;15:741-753.
DOI: 10.2147/TCRM.S198735
-
32.
Lelubre C., Anselin S., Zouaoui Boudjeltia K., Biston P., Piagnerelli M. Interpretation of C-reactive protein concentrations in critically ill patients. Biomed Res Int. 2013;2013:124021.
DOI: 10.1155/2013/124021.
-
33.
LSI Medience Corporation. PATHFAST Presepsin. Available at: www.pathfast.eu/presepsin. Accessed April 12, 2020.
-
34.
Diazyme Laboratories. Procalcitonin: a specific marker for diagnosis of bacterial infection and sepsis. Available at: www.diazyme.com/websites/diazyme/images/products/pdf/data_sheets/MK169%20-%20Procalcitonin%20PCT%20Brochure.pdf. Accessed April 12, 2020.
-
35.
Vincent J.L., Donadello K., Schmit X. Biomarkers in the critically ill patient: C-reactive protein. Crit Care Clin. 2011;27:241-251.
DOI: 10.1016/j.ccc.2010.12.010
-
36.
Christ-Crain M., Muller B. Procalcitonin in bacterial infections – hype, hope, more or less? Swiss Med Wkly. 2005;135:451460.
DOI: 10.4414/smw.2005.11169
-
37.
Káňová M., Dobiáš R., Liszková K., Frelich M., Ječmínková R., Kula R. Presepsin in the diagnostics of sepsis. Presepsin v diagnostice sepse. Vnitr Lek. 2019;65(7-8):497-505. PMID: 31487993
-
38.
Yoon S.H., Kim E.H., Kim H.Y., Ahn J.G. Presepsin as a diagnostic marker of sepsis in children and adolescents: a systemic review and meta-analysis. BMC Infect Dis. 2019;19(1):760.
DOI: 10.1186/s12879-019-4397-1
-
39.
Jereb M., Mavric M., Skvarc M., Drobnic A., Dolenc S., Planinc Strunjas N., et al. Usefulness of presepsin as diagnostic and prognostic marker of sepsis in daily clinical practice. J Infect Dev Ctries. 2019;13(11):1038-1044.
DOI: 10.3855/jidc.11764
-
40.
Bełtowski J., Jamroz A. Adrenomedullin – what do we know 10 years since its discovery? Pol J Pharmacol. 2004;56(1):5-27.
-
41.
Hinson J.P., Kapas S., Smith D.M. Adrenomedullin, a multifunctional regulatory peptide. Endocr Rev. 2000;21(2):138167.
DOI: 10.1210/edrv.21.2.0396
-
42.
Bello S., Lasierra A.B., Mincholé E., Fandos S., Ruiz M.A., Vera E., et al. Prognostic power of proadrenomedullin in community-acquired pneumonia is independent of aetiology. Eur Respir J. 2012;39(5):1144-1155.
DOI: 10.1183/09031936.00080411
-
43.
Christ-Crain M., Morgenthaler N. G., Stolz D., Müller C., Bingisser R., Harbarth S., et al. Pro-adrenomedullin to predict severity and outcome in community-acquired pneumonia [ISRCTN04176397]. Crit Care. 2006;10(3):R96.
DOI: 10.1186/cc4955
-
44.
Albrich W.C., Dusemund F., Rüegger K., Christ-Crain M., Zimmerli W., Bregenzer T., et al. Enhancement of CURB65 score with proadrenomedullin (CURB65-A) for outcome prediction in lower respiratory tract infections: derivation of a clinical algorithm. BMC Infect Dis. 2011;11:112.
DOI: 10.1186/1471-2334-11-112
-
45.
Lewis L.K., Smith M.W., Yandle T.G., Richards A.M., Nicholls M.G. Adrenomedullin(1-52) measured in human plasma by radioimmunoassay: plasma concentration, adsorption, and storage. Clin Chem. 1998;44(3):571-577. PMID: 9510864
-
46.
Rudnov V.A., Moldovanov A.V., AstafIeva M.N., Perevalova E.Yu. The clinical significance of proadrenomedulin level in blood in sepsis patients. Vestnik anesteziologii i reanimatologii. 2019;16(5):3642. Russian.
DOI: 10.21292/2078-5658-2019-16-5-36-42
-
47.
Albrich W.C., Rüegger K., Dusemund F., Bossart R., Regez K., Schild U., et al. Optimised patient transfer using an innovative multidisciplinary assessment in Kanton Aargau (OPTIMA I): an observational survey in lower respiratory tract infections. Swiss Med Wkly. 2011;141:w13237.
DOI: 10.4414/smw.2011.13237
-
48.
Krüger S., Ewig S., Giersdorf S., Hartmann O., Suttorp N., Welte T., et al. Cardiovascular and inflammatory biomarkers to predict short- and long-term survival in community-acquired pneumonia: Results from the German Competence Network, CAPNETZ. Am J Respir Crit Care Med. 2010;182(11):14261434.
DOI: 10.1164/rccm.201003-0415OC
-
49.
Guertler C., Wirz B., Christ-Crain M., Zimmerli W., Mueller B., Schuetz P. Inflammatory responses predict long-term mortality risk in community-acquired pneumonia. Eur Respir J. 2011;37(6):14391446.
DOI: 10.1183/09031936.00121510
-
50.
Huang D.T., Angus D.C., Kellum J.A., Pugh N.A., Weissfeld L.A., Struck J., et al. Midregional proadrenomedullin as a prognostic tool in community-acquired pneumonia. Chest. 2009;136(3):823831.
DOI: 10.1378/chest.08-1981
-
51.
Aliberti S., Ramirez J., Cosentini R., Brambilla A.M., Zanaboni A.M., Rossetti V., et al. Low CURB-65 is of limited value in deciding discharge of patients with community-acquired pneumonia. Respir Med. 2011;105(11):1732-1738.
DOI: 10.1016/j.rmed.2011.07.006
-
52.
Eccles S., Pincus C., Higgins B., Woodhead M., Guideline Development Group. Diagnosis and management of community and hospital acquired pneumonia in adults: summary of NICE guidance. BMJ. 2014;349:g6722.
DOI: 10.1136/bmj.g6722
-
53.
Ward C. Point-of-care C-reactive protein testing to optimise antibiotic use in a primary care urgent care centre setting. BMJ Open Qual. 2018;7(4):e000391.
DOI: 10.1136/bmjoq-2018-000391
-
54.
Metlay J.P., Waterer G.W., Long A.C., Anzueto A., Brozek J., Crothers K., et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019;200(7):e45-e67.
DOI: 10.1164/rccm.201908-1581ST
-
55.
Community-acquired pneumonia (clinical guidelines, draft version), 2018. Available at: www.antibiotic.ru/files/docs/vpproject-20181028.docx. Accessed April 12, 2020. Russian.
-
56.
Kalil A.C., Metersky M.L., Klompas M., Muscedere J., Sweeney D.A., Palmer L.B., et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016;63(5):e61-e111.
DOI: 10.1093/cid/ciw353
-
57.
Torres A., Niederman M.S., Chastre J., Ewig S., FernandezVandellos P., Hanberger H., et al. Summary of the international clinical guidelines for the management of hospital-acquired and ventilator-acquired pneumonia. ERJ Open Res. 2018;4(2). pii:00028-2018.
DOI: 10.1183/23120541.00028-2018
-
58.
Schuetz P., Chiappa V., Briel M., Greenwald J.L. Procalcitonin algorithms for antibiotic therapy decisions: a systematic review of randomized controlled trials and recommendations for clinical algorithms. Arch Intern Med. 2011;171(15):1322-1331.
DOI: 10.1001/archinternmed.2011.318
-
59.
Rhodes A., Evans L.E., Alhazzani W., Levy M.M., Antonelli M., Ferrer R., et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017;43(3):304-377.
DOI: 10.1007/s00134-017-4683-6
-
60.
Schuetz P., Bolliger R., Merker M., Christ-Crain M., Stolz D., Tamm M., et al. Procalcitonin-guided antibiotic therapy algorithms for different types of acute respiratory infections based on previous trials. Expert Rev Anti Infect Ther. 2018;16(7):555564.
DOI: 10.1080/14787210.2018.1496331
-
61.
IFCC Information Guide on COVID-19 – Monday 25 May updates. Published: Monday, May 25, 2020. Available at: www.ifcc.org/ifcc-news/2020-03-26-ifcc-information-guide-oncovid-19/.
-
62.
Algorithms of managing patients with a new coronavirus infection COVID-19 in the hospital. Clinical guidelines. M.: Burdenko main military clinical hospital, 2020, 16 p. Russian. Available at: www.gvkg.ru/files/recom-covid19.pdf. Accessed 2020. Russian.
-
63.
Canovi M., Lucchetti J., Stravalaci M., Valentino S., Bottazzi B., Salmona M., et al. A new surface plasmon resonance-based immunoassay for rapid, reproducible and sensitive quantification of pentraxin-3 in human plasma. Sensors (Basel). 2014;14:1086410875.
DOI: 10.3390/s140610864
-
64.
Hansen M.B., Rasmussen L.S., Garred P., Bidstrup D., Madsen M.B., Hyldegaard O. Pentraxin-3 as a marker of disease severity and risk of death in patients with necrotizing soft tissue infections: a nationwide, prospective, observational study. Crit Care. 2016;20:40.
DOI: 10.1186/s13054-016-1210-z
-
65.
Suberviola B., Castellanos-Ortega A., Ruiz Ruiz A., LopezHoyos M., Santibañez M. Hospital mortality prognostication in sepsis using the new biomarkers suPAR and pro-ADM in a single determination on ICU admission. Intensive Care Med. 2013;39:1945-1952.
DOI: 10.1007/s00134-013-3056-z
-
66.
Póvoa P., Coelho L., Bos L.D.J. New biomarkers for respiratory infections. Curr Opin Pulm Med. 2020;26(3):232-240.
DOI: 10.1097/MCP.0000000000000669
-
67.
Póvoa P., Salluh J.I.F., Nobre V., Martín-loeches I. Biomarker guided antibiotic therapy. What’s new? ICU Manag Pract. 2016;(1):24-28.
DOI: 10.21037/atm.2017.04.04