The value of biomarker-guided antibiotic therapy

References

• Ferrer R, Martin-Loeches I, Phillips G, et al. Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: results from a guideline-based performance improvement program. Crit Care Med. 2014;42(8):p. p. 1749–55.
   Web of Science ®Google Scholar
• Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345(19):1368–1377.
   PubMed Web of Science ®Google Scholar
• Kumar A, Haery C, Paladugu B, et al. The duration of hypotension before the initiation of antibiotic treatment is a critical determinant of survival in a murine model of escherichia coli septic shock: association with serum lactate and inflammatory cytokine levels. J Infect Dis. 2006;193(2):p. p. 251–8.
   Web of Science ®Google Scholar
• Puskarich MA, Trzeciak S, Shapiro NI, et al. Association between timing of antibiotic administration and mortality from septic shock in patients treated with a quantitative resuscitation protocol. Crit Care Med. 2011;39(9):2066–2071.
   PubMed Web of Science ®Google Scholar
• Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39(2):165–228.
   PubMed Web of Science ®Google Scholar
• Gaieski DF, Edwards JM, Kallan MJ, et al. Benchmarking the incidence and mortality of severe sepsis in the United States. Crit Care Med. 2013;41(5):p. 1167–74.
   Web of Science ®Google Scholar
• Kaukonen KM, Bailey M, Suzuki S, et al. Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012. JAMA. 2014;311(13):p. 1308–16.
   PubMed Web of Science ®Google Scholar
• Hall MJ, Williams SN, DeFrances CJ, et al. Inpatient care for septicemia or sepsis: a challenge for patients and hospitals. NCHS Data Brief. 2011;62:p. 1–8.
   PubMedGoogle Scholar
• Hoyert DL, Xu J. Deaths: preliminary data for 2011. Natl Vital Stat Rep. 2012;61(6):1–51.
   PubMedGoogle Scholar
• Gobatto AL, Besen BA, Azevedo LC. How can we estimate sepsis incidence and mortality? Shock. 2017;47(1S Suppl 1):6–11.
   PubMed Web of Science ®Google Scholar
• Perner A, Gordon AC, De Backer D, et al. Sepsis: frontiers in diagnosis, resuscitation and antibiotic therapy. Intensive Care Med. 2016;42(12):1958–1969.
   PubMed Web of Science ®Google Scholar
• Chang DW, Tseng CH, Shapiro MF. Rehospitalizations following sepsis: common and costly. Crit Care Med. 2015;43(10):2085–2093.
   PubMed Web of Science ®Google Scholar
• Donnelly JP, Hohmann SF, Wang HE. Unplanned readmissions after hospitalization for severe sepsis at academic medical center-affiliated hospitals. Crit Care Med. 2015;43(9):1916–1927.
   PubMed Web of Science ®Google Scholar
• Muller B, Harbarth S, Stolz D, et al. Diagnostic and prognostic accuracy of clinical and laboratory parameters in community-acquired pneumonia. BMC Infect Dis. 2007;7:10.
   PubMed Web of Science ®Google Scholar
• Misch F, Messmer AS, Nickel CH, et al. Impact of observation on disposition of elderly patients presenting to emergency departments with non-specific complaints. PLoS One. 2014;9(5):e98097.
   PubMed Web of Science ®Google Scholar
• Gunsolus IL, Sweeney TE, Liesenfeld O, et al. Diagnosing and managing sepsis by probing the host response to infection: advances, opportunities, and challenges. J Clin Microbiol. 2019;57(7). DOI:10.1128/JCM.00425-19.
   PubMed Web of Science ®Google Scholar
• van Engelen TSR, Wiersinga WJ, Scicluna BP, et al. Biomarkers in sepsis. Crit Care Clin. 2018;34(1):139–152.
   PubMed Web of Science ®Google Scholar
• Perner A, Rhodes A, Venkatesh B, et al. Sepsis: frontiers in supportive care, organisation and research. Intensive Care Med. 2017;43(4):496–508.
   PubMed Web of Science ®Google Scholar
• Gibot S, Béné MC, Noel R, et al. Combination biomarkers to diagnose sepsis in the critically ill patient. Am J Respir Crit Care Med. 2012;186(1):65–71.
   PubMed Web of Science ®Google Scholar
• Casserly B, Read R, Levy MM. Multimarker panels in sepsis. Crit Care Clin. 2011;27(2):391–405.
   PubMed Web of Science ®Google Scholar
• Kofoed K, Andersen O, Kronborg G, et al. Use of plasma C-reactive protein, procalcitonin, neutrophils, macrophage migration inhibitory factor, soluble urokinase-type plasminogen activator receptor, and soluble triggering receptor expressed on myeloid cells-1 in combination to diagnose infections: a prospective study. Crit Care. 2007;11(2):R38.
   PubMed Web of Science ®Google Scholar
• Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):801–810.
   PubMed Web of Science ®Google Scholar
• Mueller C, Scholer A, Laule-Kilian K, et al. Use of B-type natriuretic peptide in the evaluation and management of acute dyspnea. N Engl J Med. 2004;350(7):647–654.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Schuetz P, Aujesky D, Mueller C, et al. Biomarker-guided personalised emergency medicine for all - hope for another hype? Swiss Med Wkly. 2015;145:w14079.
   PubMed Web of Science ®Google Scholar
• Wallgren UM, Castrén M, Svensson AEV, et al. Identification of adult septic patients in the prehospital setting: a comparison of two screening tools and clinical judgment. Eur J Emerg Med. 2014;21(4):260–265.
   PubMed Web of Science ®Google Scholar
• Heuer JF, Gruschka D, Crozier TA, et al. Accuracy of prehospital diagnoses by emergency physicians: comparison with discharge diagnosis. Eur J Emerg Med. 2012;19(5):292–296.
   PubMed Web of Science ®Google Scholar
• Nemec M, Koller MT, Nickel CH, et al. Patients presenting to the emergency department with non-specific complaints: the basel non-specific complaints (BANC) study. Acad Emerg Med. 2010;17(3):284–292.
   PubMed Web of Science ®Google Scholar
• Schuetz P, Koller M, Christ-Crain M, et al. Predicting mortality with pneumonia severity scores: importance of model recalibration to local settings. Epidemiol Infect. 2008;136(12):1628–1637.
   PubMed Web of Science ®Google Scholar
• Baehni C, Meier S, Spreiter P, et al. Which patients with lower respiratory tract infections need inpatient treatment? Perceptions of physicians, nurses, patients and relatives. BMC Pulm Med. 2010;10:12.
   PubMed Web of Science ®Google Scholar
• Hohn A, Balfer N, Heising B, et al. Adherence to a procalcitonin-guided antibiotic treatment protocol in patients with severe sepsis and septic shock. Ann Intensive Care. 2018;8(1):68.
   PubMedGoogle Scholar
• de Jong E, van Oers JA, Beishuizen A, et al. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. The Lancet Infectious Diseases. 2016;16(7):819–827.
   PubMed Web of Science ®Google Scholar
• Schuetz P, Wirz Y, Sager R, et al. Effect of procalcitonin-guided antibiotic treatment on mortality in acute respiratory infections: a patient level meta-analysis. The Lancet Infectious Diseases. 2018;18(1):95–107.
   PubMed Web of Science ®Google Scholar
• van der Poll T, van de Veerdonk FL, Scicluna BP, et al. The immunopathology of sepsis and potential therapeutic targets. Nat Rev Immunol. 2017;17(7):407–420.
   PubMed Web of Science ®Google Scholar
• Henriquez-Camacho C, Losa J. Biomarkers for sepsis. Biomed Res Int. 2014;2014:547818.
   PubMed Web of Science ®Google Scholar
• Rhodes B, Furnrohr BG, Vyse TJ. C-reactive protein in rheumatology: biology and genetics. Nat Rev Rheumatol. 2011;7(5):282–289.
   PubMed Web of Science ®Google Scholar
• Paynter NP, Chasman DI, Buring JE, et al. Cardiovascular disease risk prediction with and without knowledge of genetic variation at chromosome 9p21.3. Ann Intern Med. 2009;150(2):65–72.
   PubMed Web of Science ®Google Scholar
• Gonzales R, Aagaard EM, Camargo CA, et al. C-reactive protein testing does not decrease antibiotic use for acute cough illness when compared to a clinical algorithm. J Emerg Med. 2011;41(1):1–7.
   PubMed Web of Science ®Google Scholar
• Cals JW, Butler CC, Hopstaken RM, et al. Effect of point of care testing for C reactive protein and training in communication skills on antibiotic use in lower respiratory tract infections: cluster randomised trial. BMJ. 2009;338:b1374.
   PubMed Web of Science ®Google Scholar
• Cals JW, Schot MJC, de Jong SAM, et al. Point-of-care C-reactive protein testing and antibiotic prescribing for respiratory tract infections: a randomized controlled trial. Ann Fam Med. 2010;8(2):124–133.
   PubMed Web of Science ®Google Scholar
• Watson J, Salisbury C, Whiting P, et al. Added value and cascade effects of inflammatory marker tests in UK primary care: a cohort study from the clinical practice research datalink. Br J Gen Pract. 2019;69(684):e470–e478.
   PubMed Web of Science ®Google Scholar
• Schuetz P, Christ-Crain M, Muller B. Procalcitonin and other biomarkers to improve assessment and antibiotic stewardship in infections–hope for hype? Swiss Med Wkly. 2009;139(23–24):318–326.
   PubMed Web of Science ®Google Scholar
• Christ-Crain M, Muller B. Procalcitonin in bacterial infections–hype, hope, more or less? Swiss Med Wkly. 2005;135(31–32):451–460.
   PubMed Web of Science ®Google Scholar
• Jeon K, Suh JK, Jang EJ, et al. Procalcitonin-guided treatment on duration of antibiotic therapy and cost in septic patients (PRODA): a multi-center randomized controlled trial. J Korean Med Sci. 2019;34(14):e110.
   PubMed Web of Science ®Google Scholar
• Wussler D, Kozhuharov N, Tavares Oliveira M, et al. Clinical utility of procalcitonin in the diagnosis of pneumonia. Clin Chem. 2019;65(12):1532–1542.
   PubMed Web of Science ®Google Scholar
• van der Does Y, Limper M, Jie KE, et al. Procalcitonin-guided antibiotic therapy in patients with fever in a general emergency department population: a multicentre non-inferiority randomized clinical trial (HiTEMP study). Clin Microbiol Infect. 2018;24(12):1282–1289.
   PubMed Web of Science ®Google Scholar
• Butler CC, Gillespie D, White P, et al. C-reactive protein testing to guide antibiotic prescribing for COPD exacerbations. N Engl J Med. 2019;381(2):111–120.
   PubMed Web of Science ®Google Scholar
• Groeneveld GH, van ’T Wout JW, Aarts NJ, et al. Prediction model for pneumonia in primary care patients with an acute respiratory tract infection: role of symptoms, signs, and biomarkers. BMC Infect Dis. 2019;19(1):976.
   PubMed Web of Science ®Google Scholar
• Prins HJ, Duijkers R, van der Valk P, et al. CRP-guided antibiotic treatment in acute exacerbations of COPD in hospital admissions. Eur Respir J. 2019;53(5):1802014.
   PubMed Web of Science ®Google Scholar
• Saeed K, Wilson DC, Bloos F, et al. The early identification of disease progression in patients with suspected infection presenting to the emergency department: a multi-centre derivation and validation study. Crit Care. 2019;23(1):40.
   PubMed Web of Science ®Google Scholar
• Graziadio S, O’Leary RA, Stocken DD, et al. Can mid-regional pro-adrenomedullin (MR-proADM) increase the prognostic accuracy of NEWS in predicting deterioration in patients admitted to hospital with mild to moderately severe illness? A prospective single-centre observational study. BMJ Open. 2019;8(11):e020337.
   PubMed Web of Science ®Google Scholar
• van Houten CB, Oved K, Eden E, et al. Observational multi-centre, prospective study to characterize novel pathogen-and host-related factors in hospitalized patients with lower respiratory tract infections and/or sepsis - the “TAILORED-Treatment” study. BMC Infect Dis. 2018;18(1):377.
   PubMedGoogle Scholar
• Schuetz P, Mueller B, Trampuz A. Serum procalcitonin for discrimination of blood contamination from bloodstream infection due to coagulase-negative staphylococci. Infection. 2007;35(5):352–355.
   PubMed Web of Science ®Google Scholar
• Muller F, Christ-Crain M, Bregenzer T, et al. Procalcitonin levels predict bacteremia in patients with community-acquired pneumonia: a prospective cohort trial. Chest. 2010;138(1):121–129.
   PubMed Web of Science ®Google Scholar
• van Nieuwkoop C, Bonten TN, Van’t Wout JW, et al. Procalcitonin reflects bacteremia and bacterial load in urosepsis syndrome: a prospective observational study. Crit Care. 2010;14(6):R206.
   PubMed Web of Science ®Google Scholar
• Schuetz P, Suter-Widmer I, Chaudri A, et al. Prognostic value of procalcitonin in community-acquired pneumonia. Eur Respir J. 2011;37(2):384–392.
   PubMed Web of Science ®Google Scholar
• Haeuptle J, Zaborsky R, Fiumefreddo R, et al. Prognostic value of procalcitonin in legionella pneumonia. Eur J Clin Microbiol Infect Dis. 2009;28(1):55–60.
   PubMed Web of Science ®Google Scholar
• Schuetz P, Amin DN, Greenwald JL. Role of procalcitonin in managing adult patients with respiratory tract infections. Chest. 2012;141(4):1063–1073.
   PubMed Web of Science ®Google Scholar
• Brunkhorst FM, Heinz U, Forycki ZF. Kinetics of procalcitonin in iatrogenic sepsis. Intensive Care Med. 1998;24(8):888–889.
   PubMed Web of Science ®Google Scholar
• 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(2):183–190.
   PubMed Web of Science ®Google Scholar
• Nijsten MW, Olinga P, The HT, et al. Procalcitonin behaves as a fast responding acute phase protein in vivo and in vitro. Crit Care Med. 2000;28(2):458–461.
   PubMed Web of Science ®Google Scholar
• Oberhoffer M, Stonans I, Russwurm S, et al. Procalcitonin expression in human peripheral blood mononuclear cells and its modulation by lipopolysaccharides and sepsis-related cytokines in vitro. J Lab Clin Med. 1999;134(1):49–55.
   PubMed Web of Science ®Google Scholar
• Muller B, White JC, Nylén ES, et al. Ubiquitous expression of the calcitonin-i gene in multiple tissues in response to sepsis. J Clin Endocrinol Metab. 2001;86(1):396–404.
   PubMed Web of Science ®Google Scholar
• Linscheid P, Seboek D, Nylen ES, et al. In vitro and in vivo calcitonin I gene expression in parenchymal cells: a novel product of human adipose tissue. Endocrinology. 2003;144(12):5578–5584.
   PubMed Web of Science ®Google Scholar
• Linscheid P, Seboek D, Schaer DJ, et al. Expression and secretion of procalcitonin and calcitonin gene-related peptide by adherent monocytes and by macrophage-activated adipocytes. Crit Care Med. 2004;32(8):1715–1721.
   PubMed Web of Science ®Google Scholar
• Linscheid P, Seboek D, Zulewski H, et al. Autocrine/paracrine role of inflammation-mediated calcitonin gene-related peptide and adrenomedullin expression in human adipose tissue. Endocrinology. 2005;146(6):2699–2708.
   PubMed Web of Science ®Google Scholar
• Dandona P, Nix D, Wilson MF, et al. Procalcitonin increase after endotoxin injection in normal subjects. J Clin Endocrinol Metab. 1994;79(6):1605–1608.
   PubMed Web of Science ®Google Scholar
• Sexton PM, Christopoulos G, Christopoulos A, et al. Procalcitonin has bioactivity at calcitonin receptor family complexes: potential mediator implications in sepsis. Crit Care Med. 2008;36(5):1637–1640.
   PubMed Web of Science ®Google Scholar
• Muller B, Peri G, Doni A, et al. High circulating levels of the IL-1 type II decoy receptor in critically ill patients with sepsis: association of high decoy receptor levels with glucocorticoid administration. J Leukoc Biol. 2002;72(4):643–649.
   PubMed Web of Science ®Google Scholar
• Blum CA, Nigro N, Briel M, et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 2015;385(9977):1511–1518.
   PubMed Web of Science ®Google Scholar
• Uzzan B, Cohen R, Nicolas P, et al. Procalcitonin as a diagnostic test for sepsis in critically ill adults and after surgery or trauma: a systematic review and meta-analysis. Crit Care Med. 2006;34(7):1996–2003.
   PubMed Web of Science ®Google Scholar
• Hunziker S, Hügle T, Schuchardt K, et al. The value of serum procalcitonin level for differentiation of infectious from noninfectious causes of fever after orthopaedic surgery. J Bone Joint Surg Am. 2010;92(1):138–148.
   PubMed Web of Science ®Google Scholar
• Sponholz C, Sakr Y, Reinhart K, et al. Diagnostic value and prognostic implications of serum procalcitonin after cardiac surgery: a systematic review of the literature. Crit Care. 2006;10(5):R145.
   PubMed Web of Science ®Google Scholar
• Schuetz P, Affolter B, Hunziker S, et al. Serum procalcitonin, C-reactive protein and white blood cell levels following hypothermia after cardiac arrest: a retrospective cohort study. Eur J Clin Invest. 2010;40(4):376–381.
   PubMed Web of Science ®Google Scholar
• Wang H. [Predictive value of serum procalcitonin and hypersensitive C-reactive protein levels in patients with acute cerebral infarction complicated with infection]. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2019;31(8):962–966.
   PubMedGoogle Scholar
• Ahn JH, Cho YS, Cho GC. Elevated procalcitonin levels in patients with acetaminophen intoxication: two case reports: a CARE-compliant article. Medicine (Baltimore). 2020;99(7):e18882.
   PubMed Web of Science ®Google Scholar
• Mallet M, Haq M, Tripon S, et al. Elevated procalcitonin is associated with bacterial infection during acute liver failure only when unrelated to acetaminophen intoxication. Eur J Gastroenterol Hepatol. 2017;29(7):811–816.
   PubMed Web of Science ®Google Scholar
• Christ-Crain M, Jaccard-Stolz D, Bingisser R, et al. Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial. Lancet. 2004;363(9409):600–607.
   PubMed Web of Science ®Google Scholar
• Schuetz P, Christ-Crain M, Thomann R, et al. Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. JAMA. 2009;302(10):1059–1066.
   PubMed Web of Science ®Google Scholar
• Johansen ME, Jensen JU, Lundgren JD. Antibiotics in intensive care: too little or too much? Crit Care Med. 2011;39(7):1849–1851.
   PubMed Web of Science ®Google Scholar
• Bouadma L, Luyt C-E, Tubach F, et al. Use of procalcitonin to reduce patients‘ exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet. 2010;375(9713):463–474.
   PubMed Web of Science ®Google Scholar
• Schuetz P, Beishuizen A, Broyles M, et al. Procalcitonin (PCT)-guided antibiotic stewardship: an international experts consensus on optimized clinical use. Clin Chem Lab Med. 2019;57(9):1308–1318.
   PubMed Web of Science ®Google Scholar
• Wirz Y, Meier MA, Bouadma L, et al. Effect of procalcitonin-guided antibiotic treatment on clinical outcomes in intensive care unit patients with infection and sepsis patients: a patient-level meta-analysis of randomized trials. Crit Care. 2000;28(2):191.
   Google Scholar
• Li Z, Yuan X, Yu L, et al. Procalcitonin-guided antibiotic therapy in acute exacerbation of chronic obstructive pulmonary disease: an updated meta-analysis. Medicine (Baltimore). 2019;98(32):e16775.
   PubMed Web of Science ®Google Scholar
• Peng F, Chang W, Xie J-F, et al. Ineffectiveness of procalcitonin-guided antibiotic therapy in severely critically ill patients: a meta-analysis. Int J Infect Dis. 2019;85:158–166.
   PubMed Web of Science ®Google Scholar
• Kamat IS, Ramachandran V, Eswaran H, et al., Procalcitonin to distinguish viral from bacterial pneumonia: a systematic review and meta-analysis. Clin Infect Dis. 70(3): 538–542. 2020.
   PubMed Web of Science ®Google Scholar
• Montassier E, Javaudin F, Moustafa F, et al., Guideline-based clinical assessment versus procalcitonin-guided antibiotic use in pneumonia: a pragmatic randomized trial. Ann Emerg Med. 74(4): 580–591. 2019.
   PubMed Web of Science ®Google Scholar
• Langford BJ, Beriault D, Schwartz KL, et al. A real-world assessment of procalcitonin combined with antimicrobial stewardship in a community ICU. J Crit Care. 2020;57:130–133.
   PubMed Web of Science ®Google Scholar
• Huang DT, Yealy DM, Filbin MR, et al. Procalcitonin-guided use of antibiotics for lower respiratory tract infection. N Engl J Med. 2018;379(3):236–249.
   PubMed Web of Science ®Google Scholar
• Schuetz P, Balk R, Briel M, et al. Economic evaluation of procalcitonin-guided antibiotic therapy in acute respiratory infections: a US health system perspective. Clin Chem Lab Med. 2015;53(4):583–592.
   PubMed Web of Science ®Google Scholar
• Lee CC, Kwa AL, Apisarnthanarak A, et al. Procalcitonin (PCT)-guided antibiotic stewardship in Asia-Pacific countries: adaptation based on an expert consensus meeting. Clin Chem Lab Med. 2020. DOI:10.1515/cclm-2019-1122.
   Web of Science ®Google Scholar
• Schuetz P, Muller B, Christ‐Crain M, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev. 2017;10(10):Cd007498.
   PubMedGoogle Scholar
• Kitamura K, Kangawa K, Kawamoto M, et al. Adrenomedullin: a novel hypotensive peptide isolated from human pheochromocytoma. Biochem Biophys Res Commun. 1993;192(2):553–560.
   PubMed Web of Science ®Google Scholar
• Hinson JP, Kapas S, Smith DM. Adrenomedullin, a multifunctional regulatory peptide. Endocr Rev. 2000;21(2):138–167.
   PubMed Web of Science ®Google Scholar
• Eto T. A review of the biological properties and clinical implications of adrenomedullin and proadrenomedullin N-terminal 20 peptide (PAMP), hypotensive and vasodilating peptides. Peptides. 2001;22(11):1693–1711.
   PubMed Web of Science ®Google Scholar
• Pio R, Martı́nez A, Unsworth EJ, et al. Complement factor H is a serum-binding protein for adrenomedullin, and the resulting complex modulates the bioactivities of both partners. J Biol Chem. 2001;276(15):12292–12300.
   PubMed Web of Science ®Google Scholar
• Meeran K, O’Shea D, Upton PD, et al. Circulating adrenomedullin does not regulate systemic blood pressure but increases plasma prolactin after intravenous infusion in humans: a pharmacokinetic study. J Clin Endocrinol Metab. 1997;82(1):95–100.
   PubMed Web of Science ®Google Scholar
• Lewis LK, Smith MW, Yandle TG, et al. Adrenomedullin(1-52) measured in human plasma by radioimmunoassay: plasma concentration, adsorption, and storage. Clin Chem. 1998;44(3):571–577.
   PubMed Web of Science ®Google Scholar
• Struck J, Tao C, Morgenthaler NG, et al. Identification of an adrenomedullin precursor fragment in plasma of sepsis patients. Peptides. 2004;25(8):1369–1372.
   PubMed Web of Science ®Google Scholar
• Gille J, Ostermann H, Dragu A, et al. MR-proADM: a new biomarker for early diagnosis of sepsis in burned patients. J Burn Care Res. 2017;38(5):290–298.
   PubMed Web of Science ®Google Scholar
• de Kruif MD, Lemaire LC, Giebelen IA, et al. The influence of corticosteroids on the release of novel biomarkers in human endotoxemia. Intensive Care Med. 2008;34(3):518–522.
   PubMed Web of Science ®Google Scholar
• Katan M, Fluri F, Schuetz P, et al. Midregional pro-atrial natriuretic peptide and outcome in patients with acute ischemic stroke. J Am Coll Cardiol. 2010;56(13):1045–1053.
   PubMed Web of Science ®Google Scholar
• Schultz M, Rasmussen LJH, Andersen MH, et al. Use of the prognostic biomarker suPAR in the emergency department improves risk stratification but has no effect on mortality: a cluster-randomized clinical trial (TRIAGE III). Scand J Trauma Resusc Emerg Med. 2018;26(1):69.
   PubMedGoogle Scholar
• Gonzalez Del Castillo J, Wilson DC, Clemente-Callejo C, et al. Biomarkers and clinical scores to identify patient populations at risk of delayed antibiotic administration or intensive care admission. Crit Care. 2019;23(1):335.
   PubMed Web of Science ®Google Scholar
• Temmesfeld-Wollbruck B, Hocke AC, Suttorp N, et al. Adrenomedullin and endothelial barrier function. Thromb Haemost. 2001;276(15):12292–12300.
   Google Scholar
• Pittard AJ, Hawkins WJ, Webster NR. The role of the microcirculation in the multi-organ dysfunction syndrome. Clin Intensive Care. 1994;5(4):186–190.
   PubMedGoogle Scholar
• Vigue B, Leblanc P-E, Moati F, et al. Mid-regional pro-adrenomedullin (MR-proADM), a marker of positive fluid balance in critically ill patients: results of the ENVOL study. Crit Care. 2016;20(1):363.
   PubMedGoogle Scholar
• Adlbrecht C, Hülsmann M, Strunk G, et al. Prognostic value of plasma midregional pro-adrenomedullin and C-terminal-pro-endothelin-1 in chronic heart failure outpatients. Eur J Heart Fail. 2009;11(4):361–366.
   PubMed Web of Science ®Google Scholar
• Maisel A, Mueller C, Nowak RM, et al. Midregion prohormone adrenomedullin and prognosis in patients presenting with acute dyspnea: results from the BACH (biomarkers in acute heart failure) trial. J Am Coll Cardiol. 2011;58(10):1057–1067.
   PubMed Web of Science ®Google Scholar
• Courtais C, Kuster N, Dupuy A-M, et al. Proadrenomedullin, a useful tool for risk stratification in high pneumonia severity index score community acquired pneumonia. Am J Emerg Med. 2013;31(1):215–221.
   PubMed Web of Science ®Google Scholar
• Huang DT, Angus DC, Kellum JA, et al. Midregional proadrenomedullin as a prognostic tool in community-acquired pneumonia. Chest. 2009;136(3):823–831.
   PubMed Web of Science ®Google Scholar
• Espana PP, Capelastegui A, Mar C, et al. Performance of pro-adrenomedullin for identifying adverse outcomes in community-acquired pneumonia. J Infect. 2015;70(5):457–466.
   PubMed Web of Science ®Google Scholar
• Julian-Jimenez A, Yañez MC, González-Del Castillo J, et al. Prognostic power of biomarkers for short-term mortality in the elderly patients seen in emergency departments due to infections. Enferm Infecc Microbiol Clin. 2019;37(1):11–18.
   PubMed Web of Science ®Google Scholar
• Cavallazzi R, El-Kersh K, Abu-Atherah E, et al. Midregional proadrenomedullin for prognosis in community-acquired pneumonia: a systematic review. Respir Med. 2014;108(11):1569–1580.
   PubMed Web of Science ®Google Scholar
• Renaud B, Schuetz P, Claessens Y-E, et al. Proadrenomedullin improves risk of early admission to ICU score for predicting early severe community-acquired pneumonia. Chest. 2012;142(6):1447–1454.
   PubMed Web of Science ®Google Scholar
• Elke G, Bloos F, Wilson DC, et al. The use of mid-regional proadrenomedullin to identify disease severity and treatment response to sepsis - a secondary analysis of a large randomised controlled trial. Crit Care. 2018;22(1):79.
   PubMedGoogle Scholar
• Hartmann O, Schuetz P, Albrich WC, et al. Time-dependent Cox regression: serial measurement of the cardiovascular biomarker proadrenomedullin improves survival prediction in patients with lower respiratory tract infection. Int J Cardiol. 2012;161(3):166–173.
   PubMed Web of Science ®Google Scholar
• Angeletti S, Battistoni F, Fioravanti M, et al. Procalcitonin and mid-regional pro-adrenomedullin test combination in sepsis diagnosis. Clin Chem Lab Med. 2013;51(5):1059–1067.
   PubMed Web of Science ®Google Scholar
• Angeletti S, Spoto S, Fogolari M, et al. Diagnostic and prognostic role of procalcitonin (PCT) and MR-pro-Adrenomedullin (MR-proADM) in bacterial infections. APMIS. 2015;123(9):740–748.
   PubMed Web of Science ®Google Scholar
• Spoto S, Cella E, de Cesaris M, et al. Procalcitonin and MR-proadrenomedullin combination with SOFA and qSOFA scores for sepsis diagnosis and prognosis: a diagnostic algorithm. Shock. 2018;50(1):44–52.
   PubMed Web of Science ®Google Scholar
• Albrich WC, Rüegger K, Dusemund F, et al. Biomarker-enhanced triage in respiratory infections: a proof-of-concept feasibility trial. Eur Respir J. 2013;42(4):1064–1075.
   PubMed Web of Science ®Google Scholar
• Labarere J, Schuetz P, Renaud B, et al. Validation of a clinical prediction model for early admission to the intensive care unit of patients with pneumonia. Acad Emerg Med. 2012;19(9):993–1003.
   PubMed Web of Science ®Google Scholar
• Schuetz P, Batschwaroff M, Dusemund F, et al. Effectiveness of a procalcitonin algorithm to guide antibiotic therapy in respiratory tract infections outside of study conditions: a post-study survey. Eur J Clin Microbiol Infect Dis. 2010;29(3):269–277.
   PubMed Web of Science ®Google Scholar
• Karlsson R, Thorsell A, Gomila M, et al. Discovery of Species-unique Peptide Biomarkers of Bacterial Pathogens by Tandem Mass Spectrometry-based Proteotyping. Mol Cell Proteomics. 2020;19(3):518–528.
   Google Scholar
• Chen B, Zhang D, Wang X, et al. Proteomics progresses in microbial physiology and clinical antimicrobial therapy. Eur J Clin Microbiol Infect Dis. 2017;36(3):403–413.
   PubMed Web of Science ®Google Scholar
• Pierce CG, Lopez-Ribot JL. Candidiasis drug discovery and development: new approaches targeting virulence for discovering and identifying new drugs. Expert Opin Drug Discov. 2013;8(9):1117–1126.
   PubMed Web of Science ®Google Scholar
• Oved K, Cohen A, Boico O, et al. A novel host-proteome signature for distinguishing between acute bacterial and viral infections. PLoS One. 2015;10(3):e0120012.
   PubMed Web of Science ®Google Scholar
• van Houten CB, de Groot JAH, Klein A, et al. A host-protein based assay to differentiate between bacterial and viral infections in preschool children (OPPORTUNITY): a double-blind, multicentre, validation study. Lancet Infect Dis. 2017;17(4):431–440.
   Google Scholar
• Schmerler D, Neugebauer S, Ludewig K, et al. Targeted metabolomics for discrimination of systemic inflammatory disorders in critically ill patients. J Lipid Res. 2012;53(7):1369–1375.
   Google Scholar
• Rogers AJ, McGeachie M, Baron RM, et al. Metabolomic derangements are associated with mortality in critically ill adult patients. PLoS One. 2014;9(1):e87538.
   Google Scholar
• Mayhew MB, Buturovic L, Luethy R, et al., A generalizable 29-mRNA neural-network classifier for acute bacterial and viral infections. Nat Commun. 11(1): 1177. 2020.
   PubMed Web of Science ®Google Scholar
• Boots M, Hudson PJ, Sasaki A. Large shifts in pathogen virulence relate to host population structure. Science. 2004;303(5659):842–844.
   PubMed Web of Science ®Google Scholar
• Memar MY, Baghi HB. Presepsin: a promising biomarker for the detection of bacterial infections. Biomed Pharmacother. 2019;111:649–656.
   PubMed Web of Science ®Google Scholar
• Chenevier-Gobeaux C, Borderie D, Weiss N, et al. Presepsin (sCD14-ST), an innate immune response marker in sepsis. Clin Chim Acta. 2015;450:97–103.
   Google Scholar
• Urbonas V, Eidukaitė A, Tamulienė I. The predictive value of soluble biomarkers (CD14 subtype, interleukin-2 receptor, human leucocyte antigen-G) and procalcitonin in the detection of bacteremia and sepsis in pediatric oncology patients with chemotherapy-induced febrile neutropenia. Cytokine. 2013;62(1):34–37.
   PubMed Web of Science ®Google Scholar
• Zou Q, Wen W, Zhang XC. Presepsin as a novel sepsis biomarker. World J Emerg Med. 2014;5(1):16–19.
   PubMedGoogle Scholar
• Masson S, Caironi P, Fanizza C, et al. Circulating presepsin (soluble CD14 subtype) as a marker of host response in patients with severe sepsis or septic shock: data from the multicenter, randomized ALBIOS trial. Intensive Care Med. 2015;41(1):12–20.
   PubMed Web of Science ®Google Scholar
• Kweon OJ, Choi J-H, Park SK, et al. Usefulness of presepsin (sCD14 subtype) measurements as a new marker for the diagnosis and prediction of disease severity of sepsis in the Korean population. J Crit Care. 2014;29(6):965–970.
   PubMed Web of Science ®Google Scholar
• Karlsson R, Thorsell A, Gomila M, et al. Discovery of species-unique peptide biomarkers of bacterial pathogens by tandem mass spectrometry-based proteotyping. Mol Cell Proteomics. 2020;19(3):518–528.
   PubMed Web of Science ®Google Scholar
• Basile K, Kok J, Dwyer DE. Point-of-care diagnostics for respiratory viral infections. Expert Rev Mol Diagn. 2018;18(1):75–83.
   PubMed Web of Science ®Google Scholar
• Zumla A, Al-Tawfiq JA, Enne VI, et al. Rapid point of care diagnostic tests for viral and bacterial respiratory tract infections–needs, advances, and future prospects. Lancet Infect Dis. 2014;14(11):1123–1135.
   PubMed Web of Science ®Google Scholar
• Flenker KS, Burghardt EL, Dutta N, et al. Rapid detection of urinary tract infections via bacterial nuclease activity. Mol Ther. 2017;25(6):1353–1362.
   PubMed Web of Science ®Google Scholar
• Burghardt EL, Flenker KS, Clark KC, et al. Rapid, culture-free detection of staphylococcus aureus bacteremia. PLoS One. 2016;11(6):e0157234.
   PubMed Web of Science ®Google Scholar
• Peker N, Couto N, Sinha B, et al. Diagnosis of bloodstream infections from positive blood cultures and directly from blood samples: recent developments in molecular approaches. Clin Microbiol Infect. 2018;24(9):944–955.
   PubMed Web of Science ®Google Scholar
• Oviaño M, Sparbier K, Barba MJ, et al. Universal protocol for the rapid automated detection of carbapenem-resistant Gram-negative bacilli directly from blood cultures by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF/MS). Int J Antimicrob Agents. 2016;48(6):655–660.
   PubMed Web of Science ®Google Scholar
• Candel FJ, Sá MB, Belda S, et al. Current aspects in sepsis approach. Turning things around. Rev Esp Quimioter. 2018;31(4):298–315.
   PubMed Web of Science ®Google Scholar
• Opota O, Jaton K, Greub G. Microbial diagnosis of bloodstream infection: towards molecular diagnosis directly from blood. Clin Microbiol Infect. 2015;21(4):323–331.
   PubMed Web of Science ®Google Scholar
• Akane A, Matsubara K, Nakamura H, et al. Identification of the heme compound copurified with deoxyribonucleic acid (DNA) from bloodstains, a major inhibitor of polymerase chain reaction (PCR) amplification. J Forensic Sci. 1994;39(2):362–372.
   PubMed Web of Science ®Google Scholar
• Al-Soud WA, Rådström P. Purification and characterization of PCR-inhibitory components in blood cells. J Clin Microbiol. 2001;39(2):485–493.
   PubMed Web of Science ®Google Scholar
• Stojanovic I, Schneider JE, Wei L, et al. Economic evaluation of procalcitonin-guided antibiotic therapy in acute respiratory infections: a Chinese hospital system perspective. Clin Chem Lab Med. 2017;55(4):561–570.
   PubMed Web of Science ®Google Scholar
• Lima SS, Nobre V, de Castro Romanelli RM, et al. Procalcitonin-guided protocol is not useful to manage antibiotic therapy in febrile neutropenia: a randomized controlled trial. Ann Hematol. 2016;95(7):1169–1176.
   PubMed Web of Science ®Google Scholar
• Schuetz P, Bretscher C, Bernasconi L, et al. Overview of procalcitonin assays and procalcitonin-guided protocols for the management of patients with infections and sepsis. Expert Rev Mol Diagn. 2017;17(6):593–601.
   PubMed Web of Science ®Google Scholar
• Zhydkov A, Christ-Crain M, Thomann R, et al. Utility of procalcitonin, C-reactive protein and white blood cells alone and in combination for the prediction of clinical outcomes in community-acquired pneumonia. Clin Chem Lab Med. 2015;53(4):559–566.
   PubMed Web of Science ®Google Scholar
• Oliveira CF, Oliveira CA, Botoni FA, et al. C-reactive protein (Crp) is as useful as procalcitonin (Pct) to reduce antibiotic exposure in critically-Ill patients with sepsis: a randomized clinical trial. Intensive Care Med. 2012;38:S98–S98.
   Web of Science ®Google Scholar
• Oliveira CF, Bouferrache K, Caille V, et al. The usefulness of c-reactive protein (CRP) compared to procalcitonin (PCT) to reduce antibiotic exposure in critically ill patients with sepsis: A pilot study. Intensive Care Med. 2011;37:S200.
   Web of Science ®Google Scholar