Title: Procalcitonin (PCT) As A Promising Marker For Diagnosis and Differentiation of Bacterial Infections
Authors: Eman Elsayed, Heba Elshahawy,Mohamed Mossad, Maha Mahmoud Elshafei
DOI: http://dx.doi.org/10.18535/jmscr/v4i5.36
Background: Bacteremia is a life-threatening infection whose prognosis is highly dependent on early recognition and treatment with appropriate antibiotics. Early identification of bacterial infection in patients with fever is important for prompt treatment. However, the available parameters such as C-reactive protein (CRP) and leukocyte counts are not very specific. This study was aimed to assess the diagnostic value of procalcitonin (PCT) and cholesterol for bacterial infection in febrile patients. Procalcitonin levels have been shown to distinguish between bacteremia and noninfectious inflammatory states accurately and quickly in critically ill patients. Also a decrease in plasma lipids occurs during severe sepsis and has prognostic implications in critical illness. Methods: Review of the medical records of every patient treated between May, 2014 and May, 2015 who had bacteremia caused by either Gram positive (GP) or Gram negative (GN) bacteria, and whose PCT, WBCs, CRP and cholesterol levels were measured at the onset of infection Results: 88 episodes of either GN bacteremia (n = 56) or GP bacteremia (n = 32) were included. Procalcitonin levels were found to be markedly higher in patients with GN bacteremia than in those with GP bacteremia. TLC, CRP, PCT were significantly increased, while cholesterol was significantly decreased in cases when compared to control group. Conclusion: In a critically ill patient with clinical sepsis, GN bacteremia could be associated with higher PCT values than those found in GP bacteremia, regardless of the severity of the disease. Low lipid levels, Keywords: Sepsis, Procalcitonin, C-reactive, protein, Bacteremia, cholesterol, WBCs. 1. Pierre Emmanuel Charles, Sylvain Ladoire, Serge Aho, Jean Pierre Quenot, Jean-Marc Doise, Sébastien Prin, Niels-Olivier Olsson and Bernard Blettery ;Serum procalcitonin elevation in critically ill patients at the onset of bacteremia caused by either gram negative or gram positive bacteria BMC Infectious Diseases 2008, 8:38 doi:10.1186/1471-2334-8-38 2. Dillinger RP, Levy MM, Rhodes A, et al; Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup. Surviving sepsis campaign: international guideline for management of severe sepsis and sepsis shock, 2012. Crit Care Med 2013;41:580–637. 3. Schuetz P, Albrich W, Mueller B. Procalcitonin for diagnosis of infection and guide to antibiotic decisions past, present and future. BMC Med 2011;9:107. 4. 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. 5. Hyuck Lee Korean J Procalcitonin as a biomarker of infectious diseases Intern Med 2013;28:285-291 6. Schuetz P, Briel M, Christ-Crain M, et al. Procalcitonin to guide initiation and duration of antibiotic treatment in acute respiratory infections: an individual patient data meta-analysis. Clin Infect Dis 2012;55:651-662. 7. Matthaiou DK, Ntani G, Kontogiorgi M, Poulakou G, Armaganidis A, Dimopoulos G. An ESICM systematic review and meta-analysis of procalcitonin-guided antibiotic therapy algorithms in adult critically ill patients. Intensive Care Med 2012;38:940-949. 8. Schuetz P, Albrich W, Mueller B. Procalcitonin for diagnosis of infection and guide to antibiotic decisions: past, present and future. BMC Med 2011;9:107 9. Helena Brodska´ • Karin Malı´cˇkova´ • Va´clava Ada´mkova´ •Hana Bena´kova´ • Marke´ta Markova´ Sˇtˇastna´ • Toma´sˇ ZimaSignificantly higher procalcitonin levels could differentiate Gramnegative sepsis from Gram-positive and fungal sepsis Clin Exp Med-012-0191-8 2012 10. Gilbert DN. Use of plasma procalcitonin levels as anadjunct to clinical microbiology. J Clin Microbio 2010;48:2325-2329. 11. Limper M, de Kruif MD, Duits AJ, Brandjes DP, van Gorp EC. The diagnostic role of procalcitonin and other biomarkers in discriminating infectious from noninfectious fever. J Infect 2010;60:409-416 12. Manian FA. Use of procalcitonin to guide duration of antimicrobial therapy in intensive care units: proceed with caution. Clin Infect Dis 2012;54:578. 13. Tang BM, Eslick GD, Craig JC, McLean AS. Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis. Lancet Infect Dis 2007;7:210-217 14. Aabenhus R, Jensen JU. Procalcitonin-guided antibiotic treatment of respiratory tract infections in a primary care setting: are we there yet? Prim Care Respir J2011;20:360-367. 15. Ibrahim EH, Sherman G, Ward S, Fraser VJ, Kollef MH: The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting. Chest 2000,118:146-155. 16. Christ-Crain M, Muller B: Procalcitonin in bacterial infections hype, hope, more or less? Swiss Med Wkly 2005, 135:451-460. 17. Uzzan B, Cohen R, Nicolas P, Cucherat M, Perret GY: Procalcitonin as a diagnostic test for sepsis in critically ill adults and aftersurgery or trauma: A systematic review and meta-analysis. Crit Care Med 2006, 34:1996-2003. 18. Shun Yuan Guo, MD, Yin Zhou, MD, Qing Feng Hu, PhD, Jiong Yao, PhD and Hong Wang, MD 19. Wacker C, Prkno A, Brunkhorst FM, et al. Procalcitonin as a diagnostic marker for sepsis: a system review and meta-analysis. Lancet Infect Dis 2013;12:70323–7. 20. Prkno A, Wacker C, Brunkhorst FM, Schlattmann P. Procalcitonin-guided therapy in intensive care unit patients with severe sepsis and septic shock – a systematic review and meta-analysis. Crit Care. 2013;17:R291. 21. Biller K, Fae P, Germann R, Drexel H, Walli AK, Fraunberger P. Cholesterol rather than procalcitonin or C-reactive protein predicts mortality in patients with infection. Shock. 2014;42:129-32. 22. E. Ewalds, P. Pickkers. Cholesterol as an inflammatory marker: cheap but valuable? NETH J CRIT CARE - VOLUME 20 - NO 2 - APRIL 2015 23. Stevenson EK, Rubenstein AR, Radin GT, Wiener RS, Walkey AJ. Two decades of mortality trends among patients with severe sepsis: a comparative meta-analysis. Crit Care Med. 2014;42:625-31. 24. Niven DJ, Stelfox HT, Shahpori R, Laupland KB. Fever in Adult ICUs: an interrupted 25. Meisner M. Current status of procalcitonin in the ICU. Neth J Crit Care. 2013;17:4-12. 26. Jahangiri A. High-density lipoprotein and the acute-phase response. Curr Opin Endocrinol Diabetes Obes. 2010;17:156-60. 27. Lekkou A, Moukzaki A, Siagris D, et al. Serum lipid profile, cytokineproduction, and clinical outcome in patients with severe sepsis. J Crit Care 2014;29:723-7 28. Biller K, Fae P, Germann R, Drexel H, Walli AK, Fraunberger P. Cholesterolrather than procalcitonin or C-reactive protein predicts mortality in patients with infection. Shock. 2014;42:129-32. 29. Heper Y, Akalin EH, Mistik R, et al. Evaluation of C-reactive protein, procalcitonin, tumor necrosis factor alpha, and interleukin-10 levels as diagnostic and prognostic parameters in patients with community-acquired sepsis, severe sepsis, and septic shock. Eur J Clin Microbiol Infect Dis. 2006;25:481-491. 30. Riedel S, Bourbeau P, Schwartz B, et al. Timing of specimen collection for blood cultures from febrile patients with bacteremia. J Clin Microbiol. 2008;46:1381-1385. 31. Lee CC, Chen SY, Tsai CL, et al. Prognostic valueof mortality in emergency department sepsis score,procalcitonin, and C-reactive protein in patients with sepsis at the emergency department. Shock. 2008;29:322-327 32. Karlsson H, Larsson P, Wold AE, Rudin A: Pattern of cytokine responses to gram-positive and gram-negative commensal bacteria is profoundly changed when monocytes differentiate into dendritic cells. Infect Immun 2004, 72:2671-2678. 33. Abe R, Oda S, Sadahiro T, Nakamura M, Hirayama Y, Tateishi Y(2010) Gram-negative bacteremia induces greater magnitude ofinflammatory response than gram-positive bacteremia. Crit Care14:R27 34. Charles PE, Ladoire S, Aho S, Quenot JP, Doise JM, Prin S (2008) Serum procalcitonin elevation in critically ill patients at the onset of bacteremia caused by either gram negative or gram positive bacteria. BMC Infect Dis 8:38 35. Montagna MT, Coretti C, Caggiano P (2011) Procalcitonin: a possible marker of invasive fungal infection in high risk patients? 36. J Prev Hyg 52:38–39Reinhart K, Meisner M (2011) Biomarkers in the critically ill patient: procalcitonin. Crit Care Clin 27:253–263 37. Vorwerk C, Loryman B, Coats TJ, et al. Prediction of mortality in adult emergency department patients with sepsis. Emerg Med J. 2009;26: 254-258. 38. Elson G, Dunn-Siegrist I, Daubeuf B, Pugin J: Contribution of tolllike receptors to the innate immune response to gram-negative and gram-positive bacteria. Blood 2007, 109:1574-1583. 39. Tavares E, Maldonado R, Ojeda ML, Minano FJ: Circulating inflammatory mediators during start of fever in differential diagnosis of gram-negative and gram-positive infections in leukopenic rats. Clin Diagn Lab Immunol 2005, 12:1085-1093. 40. Lee CC, Hong MY, Lee NY, Chen PL, Chang CM, Ko 23. WC. Pitfalls in using serum C-reactive protein to predict bacteremia in febrile adults in the ED. Am J Emerg Med 2012; 30 : 562-9 41. de Kruif MD, Limper M, Gerritsen H, Spek CA, Brandjes 8. DP, ten Cate H, et al. Additional value of procalcitonin for diagnosis of infection in patients with fever at the emergency department. Crit Care Med 2010; 38 : 457-63. 42. von Lilienfeld-Toal M, Dietrich MP, Glasmacher A, Lehmann 25. L, Breig P, Hahn C, et al. Markers of bacteremia in febrile neutropenic patients with hematological malignancies: procalcitonin and IL-6 are more reliable than C-reactive protein. Eur J Clin Microbiol Infect Dis 2004; 23 : 539-44.. 43. Limper M, de Kruif MD, Duits AJ, Brandjes DP, van Gorp 7. EC. The diagnostic role of procalcitonin and other biomarkers in discriminating infectious from non-infectious fever. J Infect 2010; 60 : 409-16. 44. Prat C, Sancho JM, Dominguez J, Xicoy B, Gimenez M, Ferra 31. C, et al. Evaluation of procalcitonin, neopterin, C-reactive protein, IL-6 and IL-8 as a diagnostic marker of infection in patients with febrile neutropenia. Leuk Lymphoma 2008; 49 : 1752-61. 45. Biller K, Fae P, Germann R, Drexel H, Walli AK, Fraunberger P. Cholesterol rather than procalcitonin or C-reactive protein predicts mortality in patients with infection. Shock. 2014;42:129-32. 46. Chen Y, Zhao L, Chen Y, et al. Inflammatory stress exacerbates hepatic cholesterol accumulation via disrupting cellular cholesterol export. J Gastroenterol Hepatol. 2012;27:974-84. 47. Cholesterol in the ICU: a cheap and reliable marker for illness severity? H.G. Kreeftenberg 1, A.N. Roos 1, A.J.G.H. Bindels 1, V. Scharnhorst 2 NETH J CRIT CARE - VOLUME 20 - NO 2 - APRIL 2015 48. Chiarla C, Giovannini I, Giuliante F, Zadak Z, Vellone M, Ardito F, Clemente G, Murazio M, Nuzzo G: Severe hypocholesterolemia in surgical patients, sepsis, and critical illness. J Crit Care 25:361, 2010. 49. Berbe´e JF, Havekes LM, Rensen PC: Apolipoproteins modulate the inflammatory response to lipopolysaccharide. J Endotoxin Res 11:97Y103, 2005. 50. Maja Grubera, Mirjam Christ-Craina, Daiana Stolzc, Ulrich Kellera, Christian Müllerb, Roland Bingisserb, Michael Tammc, Beat Muellera, d, Philipp Schuetza SWiSS Med Wkly Prognostic impact of plasma lipids in patients with lower respiratory tract infections – an observational study 2 0 0 9; 13 9 (11 – 12): 16 6 – 17 2 51. Murch O, Collin M, Hinds CJ, Thiemermann C. Lipoproteins in inflammation and sepsis. I. Basic science. Intensive Care Med.2007; 33:13–24Abstract
particularly low Cholesterol, pointed to bacterial infection Reflecting the severity of disease, plasma lipid levels may be a complementary tool in the diagnostic workup of patients with septicemia.References
in Patients With Sepsis Procalcitonin Is a Marker of Gram-Negative Bacteremia The American Journal of the Medical Sciences Volume 349, Number 6, June 2015
Time Series Analysis. Crit Care Med. 2013;41:1863-69.