The Clinical Challenge of Sepsis Identification and Monitoring

1. Vincent JL, Opal S, Marshall JC, Tracey KJ. Sepsis definitions: Time for change. Lancet. 2013;381: 774–775. doi: 10.1016/S0140-6736(12)61815-7 23472921

2. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315: 801–810. doi: 10.1001/jama.2016.0287 26903338

3. Vincent JL, Mira JP, Antonelli M. Sepsis: older and newer concepts. Lancet Respir Med. 2016;4(3): 237–40. doi: 10.1016/S2213-2600(15)00522-6 26917436

4. Vincent JL, Marshall JC, Namendys-Silva SA, Francois B, Martin-Loeches I, Lipman J et al. Assessment of the worldwide burden of critical illness: the intensive care over nations (ICON) audit. Lancet Respir Med. 2014;2: 380–386. doi: 10.1016/S2213-2600(14)70061-X 24740011

5. Jawad I, Luksic I, Rafnsson SB. Assessing available information on the burden of sepsis: global estimates of incidence, prevalence and mortality. J Glob Health. 2012;2: 010404. doi: 10.7189/jogh.02.010404 23198133

6. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41: 580–637. doi: 10.1097/CCM.0b013e31827e83af 23353941

7. Bai X, Yu W, Ji W, Lin Z, Tan S, Duan K et al. Early versus delayed administration of norepinephrine in patients with septic shock. Crit Care. 2014;18: 532. doi: 10.1186/s13054-014-0532-y 25277635

8. Ferrer R, Martin-Loeches I, Phillips G, Osborn TM, Townsend S, Dellinger RP 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: 1749–1755. doi: 10.1097/CCM.0000000000000330 24717459

9. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med. 2003;31: 1250–1256. 12682500

10. Laupland KB, Zahar JR, Adrie C, Schwebel C, Goldgran-Toledano D, Azoulay E et al. Determinants of temperature abnormalities and influence on outcome of critical illness. Crit Care Med. 2012;40: 145–151. doi: 10.1097/CCM.0b013e31822f061d 21926588

11. Oncu S. A clinical outline to fever in intensive care patients. Minerva Anestesiol. 2013;79: 408–418. 23370123

12. Kushimoto S, Gando S, Saitoh D, Mayumi T, Ogura H, Fujishima S et al. The impact of body temperature abnormalities on the disease severity and outcome in patients with severe sepsis: an analysis from a multicenter, prospective survey of severe sepsis. Crit Care. 2013;17: R271. doi: 10.1186/cc13106 24220071

13. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA et al. 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: 1644–1655. 1303622

14. Vincent JL, Rello J, Marshall J, Silva E, Anzueto A, Martin CD et al. International study of the prevalence and outcomes of infection in intensive care units. J A M A. 2009;302: 2323–2329. doi: 10.1001/jama.2009.1754 19952319

15. Heenen S, Jacobs F, Vincent JL. Antibiotic strategies in severe nosocomial sepsis: why do we not de-escalate more often? Crit Care Med. 2012;40: 1404–1409. doi: 10.1097/CCM.0b013e3182416ecf 22430235

16. Phua J, Ngerng W, See K, Tay C, Kiong T, Lim H et al. Characteristics and outcomes of culture-negative versus culture-positive severe sepsis. Crit Care. 2013;17: R202. doi: 10.1186/cc12896 24028771

17. Vincent JL, Brealey D, Libert N, Abidi NE, O'Dwyer M, Zacharowski K et al. Rapid Diagnosis of Infection in the Critically Ill (RADICAL), a multicenter study of molecular detection in bloodstream infections, pneumonia and sterile site infections. Crit Care Med. 2015;43: 2283–2291. doi: 10.1097/CCM.0000000000001249 26327198

18. Ljungstrom L, Enroth H, Claesson BE, Ovemyr I, Karlsson J, Froberg B et al. Clinical evaluation of commercial nucleic acid amplification tests in patients with suspected sepsis. BMC Infect Dis. 2015;15: 199. doi: 10.1186/s12879-015-0938-4 25928122

19. Su G, Fu Z, Hu L, Wang Y, Zhao Z, Yang W. 16S ribosomal ribonucleic acid gene polymerase chain reaction in the diagnosis of bloodstream infections: A systematic review and meta-analysis. PLoS ONE. 2015;10: e0127195. doi: 10.1371/journal.pone.0127195 25996771

20. Poeze M, Ramsay G, Gerlach H, Rubulotta F, Levy M. An international sepsis survey: a study of doctors' knowledge and perception about sepsis. Crit Care. 2004;8: R409–R413. 15566585

21. Zhao H, Heard SO, Mullen MT, Crawford S, Goldberg RJ, Frendl G et al. An evaluation of the diagnostic accuracy of the 1991 American College of Chest Physicians/Society of Critical Care Medicine and the 2001 Society of Critical Care Medicine/European Society of Intensive Care Medicine/American College of Chest Physicians/American Thoracic Society/Surgical Infection Society sepsis definition. Crit Care Med. 2012;40: 1700–1706. doi: 10.1097/CCM.0b013e318246b83a 22610176

22. Gaieski DF, Edwards JM, Kallan MJ, Carr BG. Benchmarking the incidence and mortality of severe sepsis in the United States. Crit Care Med. 2013;41: 1167–1174. doi: 10.1097/CCM.0b013e31827c09f8 23442987

23. Pierrakos C, Vincent JL. Sepsis biomarkers: a review. Crit Care. 2010;14: R15. doi: 10.1186/cc8872 20144219

24. Cho SY, Choi JH. Biomarkers of sepsis. Infect Chemother. 2014;46: 1–12. doi: 10.3947/ic.2014.46.1.1 24693464

25. Vincent JL, Beumier M. Diagnostic and prognostic markers in sepsis. Expert Rev Anti Infect Ther. 2013;11: 265–275. doi: 10.1586/eri.13.9 23458767

26. Reinhart K, Bauer M, Riedemann NC, Hartog CS. New approaches to sepsis: molecular diagnostics and biomarkers. Clin Microbiol Rev. 2012;25: 609–634. doi: 10.1128/CMR.00016-12 23034322

27. Tillett WS, Francis T. Serological reactions in pneumonia with a non-protein somatic fraction of pneumococcus. J Exp Med. 1930;52: 561–571. 19869788

28. Santonocito C, De L, I, Donadello K, Moussa MD, Markowicz S, Gullo A et al. C-reactive protein kinetics after major surgery. Anesth Analg. 2014;119: 624–629. doi: 10.1213/ANE.0000000000000263 24878684

29. Assicot M, Gendrel D, Carsin H, Raymond J, Guilbaud J, Bohuon C. High serum procalcitonin concentrations in patients with sepsis and infection. Lancet. 1993;341: 515–518. 8094770

30. Luzzani A, Polati E, Dorizzi R, Rungatscher A, Pavan R, Merlini A. Comparison of procalcitonin and C-reactive protein as markers of sepsis. Crit Care Med. 2003;31: 1737–1741. 12794413

31. Uzzan B, Cohen R, Nicolas P, Cucherat M, Perret GY. 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: 1996–2003. 16715031

32. Simon L, Gauvin F, Amre DK, Saint-Louis P, Lacroix J. Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. Clin Infect Dis. 2004;39: 206–217. 15307030

33. Castelli GP, Pognani C, Cita M, Paladini R. Procalcitonin as a prognostic and diagnostic tool for septic complications after major trauma. Crit Care Med. 2009;37: 1845–1849. doi: 10.1097/CCM.0b013e31819ffd5b 19384224

34. Ugarte H, Silva E, Mercan D, De Mendonca A, Vincent JL. Procalcitonin used as a marker of infection in the intensive care unit. Crit Care Med. 1999;27: 498–504. 10199528

35. Mofidi R, Suttie SA, Patil PV, Ogston S, Parks RW. The value of procalcitonin at predicting the severity of acute pancreatitis and development of infected pancreatic necrosis: systematic review. Surgery. 2009;146: 72–81. doi: 10.1016/j.surg.2009.02.013 19541012

36. Meisner M, Adina H, Schmidt J. Correlation of procalcitonin and C-reactive protein to inflammation, complications, and outcome during the intensive care unit course of multiple-trauma patients. Crit Care. 2006;10: R1. 16356205

37. Meisner M, Rauschmayer C, Schmidt J, Feyrer R, Cesnjevar R, Bredle D et al. Early increase of procalcitonin after cardiovascular surgery in patients with postoperative complications. Intensive Care Med. 2002;28: 1094–1102. 12185431

38. Christ-Crain M, Jaccard-Stolz D, Bingisser R, Gencay MM, Huber PR, Tamm M 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: 600–607. 14987884

39. Giamarellos-Bourboulis EJ, Tsangaris I, Kanni T, Mouktaroudi M, Pantelidou I, Adamis G et al. Procalcitonin as an early indicator of outcome in sepsis: a prospective observational study. J Hosp Infect. 2011;77: 58–63. doi: 10.1016/j.jhin.2010.07.026 21131099

40. Karlsson S, Heikkinen M, Pettila V, Alila S, Vaisanen S, Pulkki K et al. Predictive value of procalcitonin decrease in patients with severe sepsis: a prospective observational study. Crit Care. 2010;14: R205. doi: 10.1186/cc9327 21078153

41. Povoa P, Teixeira-Pinto AM, Carneiro AH. C-reactive protein, an early marker of community-acquired sepsis resolution: a multi-center prospective observational study. Crit Care. 2011;15: R169. doi: 10.1186/cc10313 21762483

42. Oliveira CF, Botoni FA, Oliveira CR, Silva CB, Pereira HA, Serufo JC et al. Procalcitonin versus C-reactive protein for guiding antibiotic therapy in sepsis: a randomized trial. Crit Care Med. 2013;41: 2336–2343. doi: 10.1097/CCM.0b013e31828e969f 23921272

43. Schmit X, Vincent JL. The time course of blood C-reactive protein concentrations in relation to the response to initial antimicrobial therapy in patients with sepsis. Infection. 2008;36: 213–219. doi: 10.1007/s15010-007-7077-9 18463788

44. Schuetz P, Christ-Crain M, Thomann R, Falconnier C, Wolbers M, Widmer I et al. Effect of procalcitonin-based guidelines vs standard guidelines on antibiotic use in lower respiratory tract infections: the ProHOSP randomized controlled trial. J A M A. 2009;302: 1059–1066. doi: 10.1001/jama.2009.1297 19738090

45. Heyland DK, Johnson AP, Reynolds SC, Muscedere J. Procalcitonin for reduced antibiotic exposure in the critical care setting: a systematic review and an economic evaluation. Crit Care Med. 2011;39: 1792–1799. doi: 10.1097/CCM.0b013e31821201a5 21358400

46. Jensen JU, Hein L, Lundgren B, Bestle MH, Mohr TT, Andersen MH et al. Procalcitonin-guided interventions against infections to increase early appropriate antibiotics and improve survival in the intensive care unit: a randomized trial. Crit Care Med. 2011;39: 2048–2058. doi: 10.1097/CCM.0b013e31821e8791 21572328

47. Carrico CJ, Meakins JL, Marshall JC, Fry D, Maier RV. Multiple-organ-failure syndrome. Arch Surg. 1986;121: 196–208. 3484944

48. Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W et al. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature. 2010;464: 104–107. doi: 10.1038/nature08780 20203610

49. Lord JM, Midwinter MJ, Chen YF, Belli A, Brohi K, Kovacs EJ et al. The systemic immune response to trauma: an overview of pathophysiology and treatment. Lancet. 2014;384: 1455–1465. doi: 10.1016/S0140-6736(14)60687-5 25390327

50. Kofoed K, Andersen O, Kronborg G, Tvede M, Petersen J, Eugen-Olsen J 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: R38. 17362525

51. Gibot S, Bene MC, Noel R, Massin F, Guy J, Cravoisy A et al. Combination biomarkers to diagnose sepsis in the critically ill patient. Am J Respir Crit Care Med. 2012;186: 65–71. doi: 10.1164/rccm.201201-0037OC 22538802

52. Sutherland A, Thomas M, Brandon RA, Brandon RB, Lipman J, Tang B et al. Development and validation of a novel molecular biomarker diagnostic test for the early detection of sepsis. Crit Care. 2011;15: R149. doi: 10.1186/cc10274 21682927

53. Tang BM, McLean AS, Dawes IW, Huang SJ, Lin RC. Gene-expression profiling of peripheral blood mononuclear cells in sepsis. Crit Care Med. 2009;37: 882–888. doi: 10.1097/CCM.0b013e31819b52fd 19237892

54. Pena OM, Hancock DG, Lyle NH, Linder A, Russell JA, Xia J et al. An endotoxin tolerance signature predicts sepsis and organ dysfunction at initial clinical presentation. EBioMedicine. 2014;1: 64–71. 25685830

55. Sweeney TE, Shidham A, Wong HR, Khatri P. A comprehensive time-course-based multicohort analysis of sepsis and sterile inflammation reveals a robust diagnostic gene set. Sci Transl Med. 2015;7: 287ra71. doi: 10.1126/scitranslmed.aaa5993 25972003

56. Langley RJ, Tipper JL, Bruse S, Baron RM, Tsalik EL, Huntley J et al. Integrative "omic" analysis of experimental bacteremia identifies a metabolic signature that distinguishes human sepsis from systemic inflammatory response syndromes. Am J Respir Crit Care Med. 2014;190: 445–455. doi: 10.1164/rccm.201404-0624OC 25054455

57. McHugh L, Seldon TA, Brandon RA, Kirk JT, Rapisarda A, Sutherland AJ et al. A molecular host response assay to discriminate between sepsis and infection-negative systemic inflammation in critically ill patients: Discovery and validation in independent cohorts. PLoS Med. 2015;12: e1001916. doi: 10.1371/journal.pmed.1001916 26645559