Current Infectious Disease Reports

, Volume 12, Issue 5, pp 329–335

Early Identification of Sepsis



Early diagnosis is crucial to reduce morbidity and mortality from sepsis. Clinical suspicion is the first step to diagnosis, and necessitates meticulous history taking and complete clinical examination. Special attention should be paid to identifying foci of infection. Biomarkers of host response—including acute phase proteins, procalcitonin, and various cytokines—may be useful in the diagnosis and management of patients with sepsis. Rapid and reliable detection of pathogens and their antibiotic susceptibility patterns is also of utmost importance. Many new techniques have been developed to shorten the time required for pathogen detection, including nucleic acid-based technologies (eg, polymerase chain reaction, microarrays, and hybridization). The detection of pathogen-related antigens is another approach that is useful in the diagnosis of fungal infections, targeting fungal cell wall components such as galactomannan and (1→3)-β-D-glucan.


Sepsis Early diagnosis Procalcitonin Polymerase chain reaction Multiplex Microarrays Biomarkers Hybridization Cytokines 


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Martin GS, Mannino DM, Eaton S, et al.: The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 2003, 348:1546–1554.CrossRefPubMedGoogle Scholar
  2. 2.
    Vincent JL, Rello J, Marshall J, et al.: International study of the prevalence and outcomes of infection in intensive care units. JAMA 2009, 302:2323–2329.CrossRefPubMedGoogle Scholar
  3. 3.
    Dellinger RP, Carlet JM, Masur H, et al.: Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 2004, 32:858–873.CrossRefPubMedGoogle Scholar
  4. 4.
    Hyatt JM, McKinnon PS, Zimmer GS, et al.: The importance of pharmacokinetic/pharmacodynamic surrogate markers to outcome. Focus on antibacterial agents. Clin Pharmacokinet 1995, 28:143–160.CrossRefPubMedGoogle Scholar
  5. 5.
    American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis.Crit Care Med 1992, 20:864–874.Google Scholar
  6. 6.
    Levy MM, Fink MP, Marshall JC, et al.: 2001 SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conference. Crit Care Med 2003, 31:1250–1256.CrossRefPubMedGoogle Scholar
  7. 7.
    Calandra T, Cohen J: The international sepsis forum consensus conference on definitions of infection in the intensive care unit. Crit Care Med 2005, 33:1538–1548.CrossRefPubMedGoogle Scholar
  8. 8.
    •• Sakr Y, Reinhart K: Biomarkers of host response; diagnostic purposes. In Sepsis Handbook. Edited by Dellinger RP, Carlet JM. Paris: bioMérieux Editions; 2008:94–103. This chapter provides a concise review of biomarkers of host response that could be used in the diagnosis of sepsis.Google Scholar
  9. 9.
    •• Bouadma L, Luyt CE, 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, 375:463–474. The study presents the results of a multicenter trial on the use of PCT to guide antibiotic therapy. The authors also comprehensively summarize previous trials on the same subject.CrossRefPubMedGoogle Scholar
  10. 10.
    Christ-Crain M, Stolz D, Bingisser R, et al.: Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial. Am J Respir Crit Care Med 2006, 174:84–93.CrossRefPubMedGoogle Scholar
  11. 11.
    Westh H, Lisby G, Breysse F, et al.: Multiplex real-time PCR and blood culture for identification of bloodstream pathogens in patients with suspected sepsis. Clin Microbiol Infect 2009, 15:544–551.CrossRefPubMedGoogle Scholar
  12. 12.
    •• Mancini N, Carletti S, Ghidoli N, et al.: The era of molecular and other non-culture-based methods in diagnosis of sepsis. Clin Microbiol Rev 2010, 23:235–251. This article provides a detailed review of the molecular and nonculture-based methods used in diagnosis of sepsis. Recent and commercially available assays are summarized.CrossRefPubMedGoogle Scholar
  13. 13.
    • Rea-Neto A, Youssef NC, Tuche F, et al.: Diagnosis of ventilator-associated pneumonia: a systematic review of the literature. Crit Care 2008, 12:R56. This article reviews the current methods used in the diagnosis of ventilator-associated pneumonia. A clinically oriented approach is also described and may be helpful in the diagnosis of sepsis from other causes.CrossRefPubMedGoogle Scholar
  14. 14.
    Peters RP, van Agtmael MA, Danner SA, et al.: New developments in the diagnosis of bloodstream infections. Lancet Infect Dis 2004, 4:751–760.CrossRefPubMedGoogle Scholar
  15. 15.
    Shang S, Chen Z, Yu X: Detection of bacterial DNA by PCR and reverse hybridization in the 16S rRNA gene with particular reference to neonatal septicemia. Acta Paediatr 2001, 90:179–183.CrossRefPubMedGoogle Scholar
  16. 16.
    Fenollar F, Raoult D: Molecular diagnosis of bloodstream infections caused by non-cultivable bacteria. Int J Antimicrob Agents 2007, 30(Suppl 1):S7–S15.CrossRefPubMedGoogle Scholar
  17. 17.
    Klingspor L, Loeffler J: Aspergillus PCR formidable challenges and progress. Med Mycol 2009, 47(Suppl 1):S241–S247.CrossRefPubMedGoogle Scholar
  18. 18.
    Ahmad S, Khan Z, Mustafa AS, et al.: Seminested PCR for diagnosis of candidemia: comparison with culture, antigen detection, and biochemical methods for species identification. J Clin Microbiol 2002, 40:2483–2489.CrossRefPubMedGoogle Scholar
  19. 19.
    Moreira-Oliveira MS, Mikami Y, Miyaji M, et al.: Diagnosis of candidemia by polymerase chain reaction and blood culture: prospective study in a high-risk population and identification of variables associated with development of candidemia. Eur J Clin Microbiol Infect Dis 2005, 24:721–726.CrossRefPubMedGoogle Scholar
  20. 20.
    Klingspor L, Jalal S: Molecular detection and identification of Candida and Aspergillus spp. from clinical samples using real-time PCR. Clin Microbiol Infect 2006, 12:745–753.PubMedGoogle Scholar
  21. 21.
    Hardak E, Yigla M, Avivi I, et al.: Impact of PCR-based diagnosis of invasive pulmonary aspergillosis on clinical outcome. Bone Marrow Transplant 2009, 44:595–599.CrossRefPubMedGoogle Scholar
  22. 22.
    Peters RP, van Agtmael MA, Gierveld S, et al.: Quantitative detection of Staphylococcus aureus and Enterococcus faecalis DNA in blood to diagnose bacteremia in patients in the intensive care unit. J Clin Microbiol 2007, 45:3641–3646.CrossRefPubMedGoogle Scholar
  23. 23.
    Sanchez-Jimenez MM, Cardona-Castro N: Validation of a PCR for diagnosis of typhoid fever and salmonellosis by amplification of the hilA gene in clinical samples from Colombian patients. J Med Microbiol 2004, 53:875–878.CrossRefPubMedGoogle Scholar
  24. 24.
    Rebollo MJ, San Juan GR, Folgueira D, et al.: Blood and urine samples as useful sources for the direct detection of tuberculosis by polymerase chain reaction. Diagn Microbiol Infect Dis 2006, 56:141–146.CrossRefPubMedGoogle Scholar
  25. 25.
    Song JH, Cho H, Park MY, et al.: Detection of Salmonella typhi in the blood of patients with typhoid fever by polymerase chain reaction. J Clin Microbiol 1993, 31:1439–1443.PubMedGoogle Scholar
  26. 26.
    Schabereiter-Gurtner C, Nehr M, Apfalter P, et al.: Evaluation of a protocol for molecular broad-range diagnosis of culture-negative bacterial infections in clinical routine diagnosis. J Appl Microbiol 2008, 104:1228–1237.CrossRefPubMedGoogle Scholar
  27. 27.
    Lehmann LE, Hunfeld KP, Emrich T, et al.: A multiplex real-time PCR assay for rapid detection and differentiation of 25 bacterial and fungal pathogens from whole blood samples. Med Microbiol Immunol 2008, 197:313–324.CrossRefPubMedGoogle Scholar
  28. 28.
    Marín M, Muñoz P, Sánchez M, et al.: Molecular diagnosis of infective endocarditis by real-time broad-range polymerase chain reaction (PCR) and sequencing directly from heart valve tissue. Medicine (Baltimore) 2007, 86:195–202.CrossRefGoogle Scholar
  29. 29.
    Rothman RE, Majmudar MD, Kelen GD, et al.: Detection of bacteremia in emergency department patients at risk for infective endocarditis using universal 16S rRNA primers in a decontaminated polymerase chain reaction assay. J Infect Dis 2002, 186:1677–1681.CrossRefPubMedGoogle Scholar
  30. 30.
    El Mahallawy HA, Shaker HH, Ali Helmy H, et al.: Evaluation of pan-fungal PCR assay and Aspergillus antigen detection in the diagnosis of invasive fungal infections in high risk paediatric cancer patients. Med Mycol 2006, 44:733–739.CrossRefPubMedGoogle Scholar
  31. 31.
    Vollmer T, Stormer M, Kleesiek K, et al.: Evaluation of novel broad-range real-time PCR assay for rapid detection of human pathogenic fungi in various clinical specimens. J Clin Microbiol 2008, 46:1919–1926.CrossRefPubMedGoogle Scholar
  32. 32.
    Van Burik JA, Myerson D, Schreckhise RW, et al.: Panfungal PCR assay for detection of fungal infection in human blood specimens. J Clin Microbiol 1998, 36:1169–1175.PubMedGoogle Scholar
  33. 33.
    Millar MR, Johnson G, Wilks M, et al.: Molecular diagnosis of vascular access device-associated infection in children being treated for cancer or leukaemia. Clin Microbiol Infect 2008, 14:213–220.CrossRefPubMedGoogle Scholar
  34. 34.
    Peters RP, Mohammadi T, Vandenbroucke-Grauls CM, et al.: Detection of bacterial DNA in blood samples from febrile patients: underestimated infection or emerging contamination? FEMS Immunol Med Microbiol 2004, 42:249–253.CrossRefPubMedGoogle Scholar
  35. 35.
    Yang S, Ramachandran P, Hardick A, et al.: Rapid PCR-based diagnosis of septic arthritis by early Gram-type classification and pathogen identification. J Clin Microbiol 2008, 46:1386–1390.CrossRefPubMedGoogle Scholar
  36. 36.
    Mancini N, Clerici D, Diotti R, et al.: Molecular diagnosis of sepsis in neutropenic patients with haematological malignancies. J Med Microbiol 2008, 57:601–604.CrossRefPubMedGoogle Scholar
  37. 37.
    Louie RF, Tang Z, Albertson TE, et al.: Multiplex polymerase chain reaction detection enhancement of bacteremia and fungemia. Crit Care Med 2008, 36:1487–1492.CrossRefPubMedGoogle Scholar
  38. 38.
    Corless CE, Guiver M, Borrow R, et al.: Simultaneous detection of Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae in suspected cases of meningitis and septicemia using real-time PCR. J Clin Microbiol 2001, 39:1553–1558.CrossRefPubMedGoogle Scholar
  39. 39.
    Volokhov D, Rasooly A, Chumakov K, et al.: Identification of Listeria species by microarray-based assay. J Clin Microbiol 2002, 40:4720–4728.CrossRefPubMedGoogle Scholar
  40. 40.
    Leinberger DM, Schumacher U, Autenrieth IB, et al.: Development of a DNA microarray for detection and identification of fungal pathogens involved in invasive mycoses. J Clin Microbiol 2005, 43:4943–4953.CrossRefPubMedGoogle Scholar
  41. 41.
    Shang S, Chen G, Wu Y, et al.: Rapid diagnosis of bacterial sepsis with PCR amplification and microarray hybridization in 16S rRNA gene. Pediatr Res 2005, 58:143–148.CrossRefPubMedGoogle Scholar
  42. 42.
    Uchida K, Yayama T, Kokubo Y, et al.: Direct detection of pathogens in osteoarticular infections by polymerase chain reaction amplification and microarray hybridization. J Orthop Sci 2009, 14:471–483.CrossRefPubMedGoogle Scholar
  43. 43.
    Yoo SM, Lee SY, Chang KH, et al.: High-throughput identification of clinically important bacterial pathogens using DNA microarray. Mol Cell Probes 2009, 23:171–177.CrossRefPubMedGoogle Scholar
  44. 44.
    Liu Y, Han JX, Huang HY, et al.: Development and evaluation of 16S rDNA microarray for detecting bacterial pathogens in cerebrospinal fluid. Exp Biol Med (Maywood ) 2005, 230:587–591.Google Scholar
  45. 45.
    Marlowe EM, Hogan JJ, Hindler JF, et al.: Application of an rRNA probe matrix for rapid identification of bacteria and fungi from routine blood cultures. J Clin Microbiol 2003, 41:5127–5133.CrossRefPubMedGoogle Scholar
  46. 46.
    Poppert S, Essig A, Stoehr B, et al.: Rapid diagnosis of bacterial meningitis by real-time PCR and fluorescence in situ hybridization. J Clin Microbiol 2005, 43:3390–3397.CrossRefPubMedGoogle Scholar
  47. 47.
    Hogardt M, Trebesius K, Geiger AM, et al.: Specific and rapid detection by fluorescent in situ hybridization of bacteria in clinical samples obtained from cystic fibrosis patients. J Clin Microbiol 2000, 38:818–825.PubMedGoogle Scholar
  48. 48.
    Trebesius K, Leitritz L, Adler K, et al.: Culture independent and rapid identification of bacterial pathogens in necrotising fasciitis and streptococcal toxic shock syndrome by fluorescence in situ hybridisation. Med Microbiol Immunol 2000, 188:169–175.CrossRefPubMedGoogle Scholar
  49. 49.
    Pfeiffer CD, Fine JP, Safdar N: Diagnosis of invasive aspergillosis using a galactomannan assay: a meta-analysis. Clin Infect Dis 2006, 42:1417–1427.CrossRefPubMedGoogle Scholar
  50. 50.
    Odabasi Z, Mattiuzzi G, Estey E, et al.: Beta-D-glucan as a diagnostic adjunct for invasive fungal infections: validation, cutoff development, and performance in patients with acute myelogenous leukemia and myelodysplastic syndrome. Clin Infect Dis 2004, 39:199–205.CrossRefPubMedGoogle Scholar
  51. 51.
    Pazos C, Ponton J, Del Palacio A: Contribution of (1->3)-beta-D-glucan chromogenic assay to diagnosis and therapeutic monitoring of invasive aspergillosis in neutropenic adult patients: a comparison with serial screening for circulating galactomannan. J Clin Microbiol 2005, 43:299–305.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Anesthesiology and Intensive CareFriedrich Schiller University HospitalJenaGermany

Personalised recommendations