Value of soluble TREM-1, procalcitonin, and C-reactive protein serum levels as biomarkers for detecting bacteremia among sepsis patients with new fever in intensive care units: a prospective cohort study

BMC Infectious Diseases

Lixin Xie³  Dan Feng¹  Yanhong Jia³  Peng Yan⁴  Jie Deng³  Zhaoxu Jiang³  Liling Liang³  Changting Liu²  Bingchao Han³  Longxiang Su² 

[1] Department of Medical Statistics, Chinese PLA General Hospital, 28 Fuxing Rd, Beijing, 100853, China;Department of Respiratory Diseases of South-building, Chinese PLA General Hospital, 28 Fuxing Rd, Beijing, 100853, China;Department of Respiratory Diseases, Chinese PLA General Hospital, Beijing, 100853, China;Department of Respiratory Medicine, Hainan Branch of Chinese PLA General Hospital, Sanya, Hainan Province, 572013, China

关键词: Prognosis;    Diagnosis;    Bacteremia;    Sepsis;    Fever;    Soluble triggering receptor expressed on myeloid cells 1 (sTREM-1);   

Others  :  1175334
DOI  :  10.1186/1471-2334-12-157

 received in 2011-08-07, accepted in 2012-07-18,  发布年份 2012

【 摘 要 】

Background

The purpose of this study was to explore the diagnostic value of soluble triggering receptor expressed on myeloid cells 1 (sTREM-1), procalcitonin (PCT), and C-reactive protein (CRP) serum levels for differentiating sepsis from SIRS, identifying new fever caused by bacteremia, and assessing prognosis when new fever occurred.

Methods

We enrolled 144 intensive care unit (ICU) patients: 60 with systemic inflammatory response syndrome (SIRS) and 84 with sepsis complicated by new fever at more than 48 h after ICU admission. Serum sTREM-1, PCT, and CRP levels were measured on the day of admission and at the occurrence of new fever (>38.3°C) during hospitalization. Based on the blood culture results, the patients were divided into a blood culture-positive bacteremia group (33 patients) and blood culture-negative group (51 patients). Based on 28-day survival, all patients, both blood culture-positive and -negative, were further divided into survivor and nonsurvivor groups.

Results

On ICU day 1, the sepsis group had higher serum sTREM-1, PCT, and CRP levels compared with the SIRS group (P <0.05). The areas under the curve (AUC) for these indicators were 0.868 (95% CI, 0.798–0.938), 0.729 (95% CI, 0.637–0.821), and 0.679 (95% CI, 0.578–0.771), respectively. With 108.9 pg/ml as the cut-off point for serum sTREM-1, sensitivity was 0.83 and specificity was 0.81. There was no statistically significant difference in serum sTREM-1 or PCT levels between the blood culture-positive and -negative bacteremia groups with ICU-acquired new fever. However, the nonsurvivors in the blood culture-positive bacteremia group had higher levels of serum sTREM-1 and PCT (P <0.05), with a prognostic AUC for serum sTREM-1 of 0.868 (95% CI, 0.740–0.997).

Conclusions

Serum sTREM-1, PCT, and CRP levels each have a role in the early diagnosis of sepsis. Serum sTREM-1, with the highest sensitivity and specificity of all indicators studied, is especially notable. sTREM-1, PCT, and CRP levels are of no use in determining new fever caused by bacteremia in ICU patients, but sTREM-1 levels reflect the prognosis of bacteremia.

Trial registration

ClinicalTrial.gov identifier NCT01410578

【 授权许可】

   
2012 Su et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

【 参考文献 】

• [1]Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR: Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001, 29(7):1303-1310.
• [2]Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB: Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 2004, 39(3):309-317.
• [3]Bates DW, Sands K, Miller E, Lanken PN, Hibberd PL, Graman PS, Schwartz JS, Kahn K, Snydman DR, Parsonnet J, et al.: Predicting bacteremia in patients with sepsis syndrome. Academic Medical Center Consortium Sepsis Project Working Group. J Infect Dis 1997, 176(6):1538-1551.
• [4]Bossink AW, Groeneveld J, Hack CE, Thijs LG: Prediction of mortality in febrile medical patients: How useful are systemic inflammatory response syndrome and sepsis criteria? Chest 1998, 113(6):1533-1541.
• [5]Weinstein MP, Towns ML, Quartey SM, Mirrett S, Reimer LG, Parmigiani G, Reller LB: The clinical significance of positive blood cultures in the 1990s: a prospective comprehensive evaluation of the microbiology, epidemiology, and outcome of bacteremia and fungemia in adults. Clin Infect Dis 1997, 24(4):584-602.
• [6]Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M: Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001, 345(19):1368-1377.
• [7]Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM, et al.: Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 2004, 32(3):858-873.
• [8]Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 1992, 101(6):1644-1655.
• [9]Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G: 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003, 31(4):1250-1256.
• [10]Livermore DM JD, Reacher M, et al.: CDC definitions of nosocomial infections. APIC infection control and applied epidemiology:principles and practice. , ; 1996:A-1-A-20.
• [11]Horan TC, Andrus M, Dudeck MA: CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control 2008, 36(5):309-332.
• [12]De La Rosa GD, Valencia ML, Arango CM, Gomez CI, Garcia A, Ospina S, Osorno S, Henao A, Jaimes FA: Toward an operative diagnosis in sepsis: a latent class approach. BMC Infect Dis 2008, 8:18. BioMed Central Full Text
• [13]Jaimes F, Arango C, Ruiz G, Cuervo J, Botero J, Velez G, Upegui N, Machado F: Predicting bacteremia at the bedside. Clin Infect Dis 2004, 38(3):357-362.
• [14]Marik PE: Fever in the ICU. Chest 2000, 117(3):855-869.
• [15]O'Grady NP, Barie PS, Bartlett J, Bleck T, Garvey G, Jacobi J, Linden P, Maki DG, Nam M, Pasculle W, et al.: Practice parameters for evaluating new fever in critically ill adult patients. Crit Care Med 1998, 26(2):392-408.
• [16]O'Grady NP, Barie PS, Bartlett JG, Bleck T, Carroll K, Kalil AC, Linden P, Maki DG, Nierman D, Pasculle W, et al.: Guidelines for evaluation of new fever in critically ill adult patients: 2008 update from the American College of Critical Care Medicine and the Infectious Diseases Society of America. Crit Care Med 2008, 36(4):1330-1349.
• [17]Dimopoulos G, Falagas ME: Approach to the febrile patient in the ICU. Infect Dis Clin North Am 2009, 23(3):471-484.
• [18]Towns ML, Jarvis WR, Hsueh PR: Guidelines on blood cultures. J Microbiol Immunol Infect 2010, 43(4):347-349.
• [19]Richter SS, Beekmann SE, Croco JL, Diekema DJ, Koontz FP, Pfaller MA, Doern GV: Minimizing the workup of blood culture contaminants: implementation and evaluation of a laboratory-based algorithm. J Clin Microbiol 2002, 40(7):2437-2444.
• [20]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.
• [21]Gibot S, Kolopp-Sarda MN, Bene MC, Cravoisy A, Levy B, Faure GC, Bollaert PE: Plasma level of a triggering receptor expressed on myeloid cells-1: its diagnostic accuracy in patients with suspected sepsis. Ann Intern Med 2004, 141(1):9-15.
• [22]Gibot S, Cravoisy A, Levy B, Bene MC, Faure G, Bollaert PE: Soluble triggering receptor expressed on myeloid cells and the diagnosis of pneumonia. N Engl J Med 2004, 350(5):451-458.
• [23]Liu CL, Hsieh WY, Wu CL, Kuo HT, Lu YT: Triggering receptor expressed on myeloid cells-1 in pleural effusions: a marker of inflammatory disease. Respir Med 2007, 101(5):903-909.
• [24]Collins CE, La DT, Yang HT, Massin F, Gibot S, Faure G, Stohl W: Elevated synovial expression of triggering receptor expressed on myeloid cells 1 in patients with septic arthritis or rheumatoid arthritis. Ann Rheum Dis 2009, 68(11):1768-1774.
• [25]Determann RM, Weisfelt M, de Gans J, van der Ende A, Schultz MJ, van de Beek D: Soluble triggering receptor expressed on myeloid cells 1: a biomarker for bacterial meningitis. Intensive Care Med 2006, 32(8):1243-1247.
• [26]Kusanovic JP, Romero R, Chaiworapongsa T, Mittal P, Mazaki-Tovi S, Vaisbuch E, Erez O, Gotsch F, Than NG, Edwin SS, et al.: Amniotic fluid sTREM-1 in normal pregnancy, spontaneous parturition at term and preterm, and intra-amniotic infection/inflammation. J Matern Fetal Neonatal Med 2010, 23(1):34-47.
• [27]Determann RM, van Till JW, van Ruler O, van Veen SQ, Schultz MJ, Boermeester MA: sTREM-1 is a potential useful biomarker for exclusion of ongoing infection in patients with secondary peritonitis. Cytokine 2009, 46(1):36-42.
• [28]Su LX, Feng L, Zhang J, Xiao YJ, Jia YH, Yan P, Feng D, Xie LX: Diagnostic value of urine sTREM-1 for sepsis and relevant acute kidney injuries: a prospective study. Crit Care 2011, 15(5):R250. BioMed Central Full Text
• [29]Zhang J, She D, Feng D, Jia Y, Xie L: Dynamic changes of serum soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) reflect sepsis severity and can predict prognosis: a prospective study. BMC Infect Dis 2011, 11:53. BioMed Central Full Text
• [30]Gibot S, Cravoisy A, Kolopp-Sarda MN, Bene MC, Faure G, Bollaert PE, Levy B: Time-course of sTREM (soluble triggering receptor expressed on myeloid cells)-1, procalcitonin, and C-reactive protein plasma concentrations during sepsis. Crit Care Med 2005, 33(4):792-796.
• [31]Oczenski W, Fitzgerald RD, Schwarz S: Procalcitonin: a new parameter for the diagnosis of bacterial infection in the peri-operative period. Eur J Anaesthesiol 1998, 15(2):202-209.
• [32]Christ-Crain M, Muller B: Procalcitonin in bacterial infections–hype, hope, more or less? Swiss Med Wkly 2005, 135(31–32):451-460.
• [33]Bloos F, Marshall JC, Dellinger RP, Vincent JL, Gutierrez G, Rivers E, Balk RA, Laterre PF, Angus DC, Reinhart K, et al.: Multinational, observational study of procalcitonin in ICU patients with pneumonia requiring mechanical ventilation: a multicenter observational study. Crit Care 2011, 15(2):R88. BioMed Central Full Text
• [34]Giamarellos-Bourboulis EJ, Tsangaris I, Kanni T, Mouktaroudi M, Pantelidou I, Adamis G, Atmatzidis S, Chrisofos M, Evangelopoulou V, Frantzeskaki F, et al.: Procalcitonin as an early indicator of outcome in sepsis: a prospective observational study. J Hosp Infect 2011, 77(1):58-63.
• [35]Ruiz-Laiglesia FJ, Torrubia-Perez C, Amiguet-Garcia JA, Fiteni-Mera I: Value of C-reactive protein for detecting bacteremia in febrile patients. Presse Med 1996, 25(24):1105-1108.
• [36]Povoa P: C-reactive protein: a valuable marker of sepsis. Intensive Care Med 2002, 28(3):235-243.
• [37]Wyllie DH, Bowler IC, Peto TE: Bacteraemia prediction in emergency medical admissions: role of C reactive protein. J Clin Pathol 2005, 58(4):352-356.
• [38]Lee CC, Hong MY, Lee NY, Chen PL, Chang CM, Ko WC: Pitfalls in using serum C-reactive protein to predict bacteremia in febrile adults in the ED. Am J Emerg Med 2012, 30(4):562-569.
• [39]Rivera-Chavez FA, Minei JP: Soluble triggering receptor expressed on myeloid cells-1 is an early marker of infection in the surgical intensive care unit. Surg Infect (Larchmt) 2009, 10(5):435-439.
• [40]Porfyridis I, Plachouras D, Karagianni V, Kotanidou A, Papiris SA, Giamarellou H, Giamarellos-Bourboulis EJ: Diagnostic value of triggering receptor expressed on myeloid cells-1 and C-reactive protein for patients with lung infiltrates: an observational study. BMC Infect Dis 2010, 10:286. BioMed Central Full Text
• [41]Jiyong J, Tiancha H, Wei C, Huahao S: Diagnostic value of the soluble triggering receptor expressed on myeloid cells-1 in bacterial infection: a meta-analysis. Intensive Care Med 2009, 35(4):587-595.
• [42]Latour-Perez J, Alcala-Lopez A, Garcia-Garcia MA, Sanchez-Hernandez JF, Abad-Terrado C, Viedma-Contreras JA, Masia M, Gonzalez-Tejera M, Arizo-Leon D, Porcar MJ, et al.: Diagnostic accuracy of sTREM-1 to identify infection in critically ill patients with systemic inflammatory response syndrome. Clin Biochem 2010, 43(9):720-724.
• [43]Bopp C, Hofer S, Bouchon A, Zimmermann JB, Martin E, Weigand MA: Soluble TREM-1 is not suitable for distinguishing between systemic inflammatory response syndrome and sepsis survivors and nonsurvivors in the early stage of acute inflammation. Eur J Anaesthesiol 2009, 26(6):504-507.
• [44]Adib-Conquy M, Monchi M, Goulenok C, Laurent I, Thuong M, Cavaillon JM, Adrie C: Increased plasma levels of soluble triggering receptor expressed on myeloid cells 1 and procalcitonin after cardiac surgery and cardiac arrest without infection. Shock 2007, 28(4):406-410.
• [45]Barati M, Bashar FR, Shahrami R, Zadeh MH, Taher MT, Nojomi M: Soluble triggering receptor expressed on myeloid cells 1 and the diagnosis of sepsis. J Crit Care 2010, 25(2):362 e361-366.
• [46]Kofoed K, Andersen O, Kronborg G, Tvede M, Petersen J, Eugen-Olsen J, Larsen K: 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. BioMed Central Full Text
• [47]Riedel S, Melendez JH, An AT, Rosenbaum JE, Zenilman JM: Procalcitonin as a marker for the detection of bacteremia and sepsis in the emergency department. Am J Clin Pathol 2011, 135(2):182-189.
• [48]Kim MH, Lim G, Kang SY, Lee WI, Suh JT, Lee HJ: Utility of procalcitonin as an early diagnostic marker of bacteremia in patients with acute fever. Yonsei Med J 2011, 52(2):276-281.
• [49]Lai CC, Tan CK, Chen SY, Wang CY, Liu WL, Hou CC, Hsueh PR: Diagnostic performance of procalcitonin for bacteremia in patients with bacterial infection at the emergency department. J Infect 2010, 61(6):512-515.
• [50]Blijlevens NM, Donnelly JP, Meis JF, De Keizer MH, De Pauw BE: Procalcitonin does not discriminate infection from inflammation after allogeneic bone marrow transplantation. Clin Diagn Lab Immunol 2000, 7(6):889-892.
• [51]Ruiz-Gonzalez A, Esquerda A, Falguera M, Abdulghani N, Cabezas P, Bielsa S, Porcel JM: Triggering receptor (TREM-1) expressed on myeloid cells predicts bacteremia better than clinical variables in community-acquired pneumonia. Respirology , 16(2):321-325.
• [52]Rangel-Frausto MS, Pittet D, Costigan M, Hwang T, Davis CS, Wenzel RP: The natural history of the systemic inflammatory response syndrome (SIRS). A prospective study. JAMA : the journal of the American Medical Association 1995, 273(2):117-123.
• [53]Sands KE, Bates DW, Lanken PN, Graman PS, Hibberd PL, Kahn KL, Parsonnet J, Panzer R, Orav EJ, Snydman DR, et al.: Epidemiology of sepsis syndrome in 8 academic medical centers. JAMA 1997, 278(3):234-240.