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Developments for improved diagnosis of bacterial bloodstream infections

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Abstract

Bloodstream infections (BSIs) are associated with high mortality and increased healthcare costs. Optimal management of BSI depends on several factors including recognition of the disease, laboratory tests and treatment. Rapid and accurate identification of the etiologic agent is crucial to be able to initiate pathogen specific antibiotic therapy and decrease mortality rates. Furthermore, appropriate treatment might slow down the emergence of antibiotic resistant strains. Culture-based methods are still considered to be the “gold standard” for the detection and identification of pathogens causing BSI. Positive blood cultures are used for Gram-staining. Subsequently, positive blood culture material is subcultured on solid media, and (semi-automated) biochemical testing is performed for species identification. Finally, a complete antibiotic susceptibility profile can be provided based on cultured colonies, which allows the start of pathogen-tailored antibiotic therapy. This conventional workflow is extremely time-consuming and can take up to several days. Furthermore, fastidious and slow-growing microorganisms, as well as antibiotic pre-treated samples can lead to false-negative results. The main aim of this review is to present different strategies to improve the conventional laboratory diagnostic steps for BSI. These approaches include protein-based (MALDI-TOF mass spectrometry) and nucleic acid-based (polymerase chain reaction [PCR]) identification from subculture, blood cultures, and whole blood to decrease time to results. Pathogen enrichment and DNA isolation methods, to enable optimal pathogen DNA recovery from whole blood, are described. In addition, the use of biomarkers as patient pre-selection tools for molecular assays are discussed.

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References

  1. Libman E (1897) Weitere Mitteilungen über die Streptokokken-enteritis bei Säuglingen. Zentralbl Bakteriol XXII:376

    Google Scholar 

  2. Institute CaLS (2007) Principles and procedures for blood cultures; approved guidline. CLSI Document M47-A (ISBN 1-56238-641-7)

  3. Kumar A, Ellis P, Arabi Y, Roberts D, Light B, Parrillo JE, Dodek P, Wood G, Simon D, Peters C, Ahsan M, Chateau D (2009) Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest 136(5):1237–1248

    PubMed  Google Scholar 

  4. Lim SM, Webb SA (2005) Nosocomial bacterial infections in intensive care units. I: organisms and mechanisms of antibiotic resistance. Anaesthesia 60(9):887–902

    PubMed  CAS  Google Scholar 

  5. Kerremans JJ, van der Bij AK, Goessens W, Verbrugh HA, Vos MC (2009) Immediate incubation of blood cultures outside routine laboratory hours of operation accelerates antibiotic switching. J Clin Microbiol 47(11):3520–3523

    PubMed  CAS  PubMed Central  Google Scholar 

  6. Spraycar M (1995) Stedman’s Medical Dictionary. Williams & Wilkins, Baltimore, MD

  7. Weinstein MP, Towns ML, Quartey SM, Mirrett S, Reimer LG, Parmigiani G, Reller LB (1997) 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 24(4):584–602

    PubMed  CAS  Google Scholar 

  8. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ (1992) 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 101(6):1644–1655

    PubMed  CAS  Google Scholar 

  9. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G (2003) 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 31(4):1250–1256

    PubMed  Google Scholar 

  10. Lever A, Mackenzie I (2007) Sepsis: definition, epidemiology, and diagnosis. BMJ 335(7625):879–883

    PubMed  CAS  PubMed Central  Google Scholar 

  11. Valles J, Palomar M, Alvarez-Lerma F, Rello J, Blanco A, Garnacho-Montero J, Martin-Loeches I (2013) Evolution over a 15-year period of clinical characteristics and outcomes of critically ill patients with community-acquired bacteremia. Crit Care Med 41(1):76–83

    PubMed  Google Scholar 

  12. van Gestel A, Bakker J, Veraart CP, van Hout BA (2004) Prevalence and incidence of severe sepsis in Dutch intensive care units. Crit Care 8(4):R153–R162

    PubMed  PubMed Central  Google Scholar 

  13. CDC (1992) Report of mortality statistics. Mon Vital Stat Rep 40(11):1–23

    Google Scholar 

  14. Engel C, Brunkhorst FM, Bone HG, Brunkhorst R, Gerlach H, Grond S, Gruendling M, Huhle G, Jaschinski U, John S, Mayer K, Oppert M, Olthoff D, Quintel M, Ragaller M, Rossaint R, Stuber F, Weiler N, Welte T, Bogatsch H, Hartog C, Loeffler M, Reinhart K (2007) Epidemiology of sepsis in Germany: results from a national prospective multicenter study. Intensive Care Med 33(4):606–618

    PubMed  Google Scholar 

  15. Alberti C, Brun-Buisson C, Burchardi H, Martin C, Goodman S, Artigas A, Sicignano A, Palazzo M, Moreno R, Boulme R, Lepage E, Le Gall R (2002) Epidemiology of sepsis and infection in ICU patients from an international multicentre cohort study. Intensive Care Med 28(2):108–121

    PubMed  Google Scholar 

  16. Angus DC, Wax RS (2001) Epidemiology of sepsis: an update. Crit Care Med 29(7 Suppl):S109–S116

    PubMed  CAS  Google Scholar 

  17. Garrouste-Orgeas M, Timsit JF, Tafflet M, Misset B, Zahar JR, Soufir L, Lazard T, Jamali S, Mourvillier B, Cohen Y, De Lassence A, Azoulay E, Cheval C, Descorps-Declere A, Adrie C, Costa de Beauregard MA, Carlet J (2006) Excess risk of death from intensive care unit-acquired nosocomial bloodstream infections: a reappraisal. Clin Infect Dis 42(8):1118–1126

    PubMed  Google Scholar 

  18. Kim PW, Perl TM, Keelaghan EF, Langenberg P, Perencevich EN, Harris AD, Song X, Roghmann MC (2005) Risk of mortality with a bloodstream infection is higher in the less severely ill at admission. Am J Respir Crit Care Med 171(6):616–620

    PubMed  Google Scholar 

  19. Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB (2004) Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 39(3):309–317

    PubMed  Google Scholar 

  20. Annane D, Bellissant E, Cavaillon JM (2005) Septic shock. Lancet 365(9453):63–78

    PubMed  CAS  Google Scholar 

  21. Shoham S, Marwaha S (2010) Invasive fungal infections in the ICU. J Intensive Care Med 25(2):78–92

    PubMed  Google Scholar 

  22. Bos MM, Smeets LS, Dumay I, de Jonge E (2013) Bloodstream infections in patients with or without cancer in a large community hospital. Infection 41(5):949–958

    PubMed  CAS  Google Scholar 

  23. Mermel LA, Maki DG (1993) Detection of bacteremia in adults: consequences of culturing an inadequate volume of blood. Ann Intern Med 119(4):270–272

    PubMed  CAS  Google Scholar 

  24. Yagupsky P, Nolte FS (1990) Quantitative aspects of septicemia. Clin Microbiol Rev 3(3):269–279

    PubMed  CAS  PubMed Central  Google Scholar 

  25. Jonsson B, Nyberg A, Henning C (1993) Theoretical aspects of detection of bacteraemia as a function of the volume of blood cultured. APMIS 101(8):595–601

    PubMed  CAS  Google Scholar 

  26. Kennaugh JK, Gregory WW, Powell KR, Hendley JO (1984) The effect of dilution during culture on detection of low concentrations of bacteria in blood. Pediatr Infect Dis 3(4):317–318

    PubMed  CAS  Google Scholar 

  27. Bouza E, Sousa D, Rodriguez-Creixems M, Lechuz JG, Munoz P (2007) Is the volume of blood cultured still a significant factor in the diagnosis of bloodstream infections? J Clin Microbiol 45(9):2765–2769

    PubMed  PubMed Central  Google Scholar 

  28. Cockerill FR 3rd, Wilson JW, Vetter EA, Goodman KM, Torgerson CA, Harmsen WS, Schleck CD, Ilstrup DM, Washington JA 2nd, Wilson WR (2004) Optimal testing parameters for blood cultures. Clin Infect Dis 38(12):1724–1730

    PubMed  Google Scholar 

  29. Gonsalves WI, Cornish N, Moore M, Chen A, Varman M (2009) Effects of volume and site of blood draw on blood culture results. J Clin Microbiol 47(11):3482–3485

    PubMed  PubMed Central  Google Scholar 

  30. Hall MM, Ilstrup DM, Washington JA 2nd (1976) Effect of volume of blood cultured on detection of bacteremia. J Clin Microbiol 3(6):643–645

    PubMed  CAS  PubMed Central  Google Scholar 

  31. Tenney JH, Reller LB, Mirrett S, Wang WL, Weinstein MP (1982) Controlled evaluation of the volume of blood cultured in detection of bacteremia and fungemia. J Clin Microbiol 15(4):558–561

    PubMed  CAS  PubMed Central  Google Scholar 

  32. Valles J, Rello J, Ochagavia A, Garnacho J, Alcala MA (2003) Community-acquired bloodstream infection in critically ill adult patients: impact of shock and inappropriate antibiotic therapy on survival. Chest 123(5):1615–1624

    PubMed  Google Scholar 

  33. Harbarth S, Garbino J, Pugin J, Romand JA, Lew D, Pittet D (2003) Inappropriate initial antimicrobial therapy and its effect on survival in a clinical trial of immunomodulating therapy for severe sepsis. Am J Med 115(7):529–535

    PubMed  Google Scholar 

  34. Shorr AF, Micek ST, Welch EC, Doherty JA, Reichley RM, Kollef MH (2011) Inappropriate antibiotic therapy in Gram-negative sepsis increases hospital length of stay. Crit Care Med 39(1):46–51

    PubMed  CAS  Google Scholar 

  35. Ammerlaan HS, Harbarth S, Buiting AG, Crook DW, Fitzpatrick F, Hanberger H, Herwaldt LA, van Keulen PH, Kluytmans JA, Kola A, Kuchenbecker RS, Lingaas E, Meessen N, Morris-Downes MM, Pottinger JM, Rohner P, dos Santos RP, Seifert H, Wisplinghoff H, Ziesing S, Walker AS, Bonten MJ (2013) Secular trends in nosocomial bloodstream infections: antibiotic-resistant bacteria increase the total burden of infection. Clin Infect Dis 56(6):798–805

    PubMed  CAS  Google Scholar 

  36. de Kraker ME, Jarlier V, Monen JC, Heuer OE, van de Sande N, Grundmann H (2013) The changing epidemiology of bacteraemias in Europe: trends from the European Antimicrobial Resistance Surveillance System. Clin Microbiol Infect 19(9):860–868

    PubMed  Google Scholar 

  37. Kellogg JA, Manzella JP, Bankert DA (2000) Frequency of low-level bacteremia in children from birth to fifteen years of age. J Clin Microbiol 38(6):2181–2185

    PubMed  CAS  PubMed Central  Google Scholar 

  38. Engler HD, Fahle GA, Gill VJ (1996) Clinical evaluation of the BacT/Alert and isolator aerobic blood culture systems. Am J Clin Pathol 105(6):774–781

    PubMed  CAS  Google Scholar 

  39. McDonald LC, Fune J, Gaido LB, Weinstein MP, Reimer LG, Flynn TM, Wilson ML, Mirrett S, Reller LB (1996) Clinical importance of increased sensitivity of BacT/Alert FAN aerobic and anaerobic blood culture bottles. J Clin Microbiol 34(9):2180–2184

    PubMed  CAS  PubMed Central  Google Scholar 

  40. Weinstein MP, Mirrett S, Reimer LG, Wilson ML, Smith-Elekes S, Chuard CR, Joho KL, Reller LB (1995) Controlled evaluation of BacT/Alert standard aerobic and FAN aerobic blood culture bottles for detection of bacteremia and fungemia. J Clin Microbiol 33(4):978–981

    PubMed  CAS  PubMed Central  Google Scholar 

  41. Akan OA, Yildiz E (2006) Comparison of the effect of delayed entry into 2 different blood culture systems (BACTEC 9240 and BacT/ALERT 3D) on culture positivity. Diagn Microbiol Infect Dis 54(3):193–196

    PubMed  Google Scholar 

  42. Sautter RL, Bills AR, Lang DL, Ruschell G, Heiter BJ, Bourbeau PP (2006) Effects of delayed-entry conditions on the recovery and detection of microorganisms from BacT/ALERT and BACTEC blood culture bottles. J Clin Microbiol 44(4):1245–1249

    PubMed  CAS  PubMed Central  Google Scholar 

  43. Schwetz I, Hinrichs G, Reisinger EC, Krejs GJ, Olschewski H, Krause R (2007) Delayed processing of blood samples influences time to positivity of blood cultures and results of Gram stain-acridine orange leukocyte Cytospin test. J Clin Microbiol 45(8):2691–2694

    PubMed  CAS  PubMed Central  Google Scholar 

  44. Piette A, Verschraegen G (2009) Role of coagulase-negative staphylococci in human disease. Vet Microbiol 134(1–2):45–54

    PubMed  CAS  Google Scholar 

  45. Bates DW, Lee TH (1992) Rapid classification of positive blood cultures. Prospective validation of a multivariate algorithm. JAMA 267(14):1962–1966

    PubMed  CAS  Google Scholar 

  46. Hall KK, Lyman JA (2006) Updated review of blood culture contamination. Clin Microbiol Rev 19(4):788–802

    PubMed  PubMed Central  Google Scholar 

  47. Surdulescu S, Utamsingh D, Shekar R (1998) Phlebotomy teams reduce blood-culture contamination rate and save money. Clin Perform Qual Healthc 6(2):60–62

    CAS  Google Scholar 

  48. Weinbaum FI, Lavie S, Danek M, Sixsmith D, Heinrich GF, Mills SS (1997) Doing it right the first time: quality improvement and the contaminant blood culture. J Clin Microbiol 35(3):563–565

    PubMed  CAS  PubMed Central  Google Scholar 

  49. Trubiano JA, Holmes NE, Williams DS, Ng J, Chua K, Howden BP (2012) Coxiella burnetii endocarditis after Q fever vaccination. J Med Microbiol 61(Pt 12):1775–1779

    PubMed  Google Scholar 

  50. Glerant JC, Hellmuth D, Schmit JL, Ducroix JP, Jounieaux V (1999) Utility of blood cultures in community-acquired pneumonia requiring hospitalization: influence of antibiotic treatment before admission. Respir Med 93(3):208–212

    PubMed  CAS  Google Scholar 

  51. Grace CJ, Lieberman J, Pierce K, Littenberg B (2001) Usefulness of blood culture for hospitalized patients who are receiving antibiotic therapy. Clin Infect Dis 32(11):1651–1655

    PubMed  CAS  Google Scholar 

  52. McKenzie R, Reimer LG (1987) Effect of antimicrobials on blood cultures in endocarditis. Diagn Microbiol Infect Dis 8(3):165–172

    PubMed  CAS  Google Scholar 

  53. Zadoks RN, Watts JL (2009) Species identification of coagulase-negative staphylococci: genotyping is superior to phenotyping. Vet Microbiol 134(1–2):20–28

    PubMed  CAS  Google Scholar 

  54. van Veen SQ, Claas EC, Kuijper EJ (2010) High-throughput identification of bacteria and yeast by matrix-assisted laser desorption ionization-time of flight mass spectrometry in conventional medical microbiology laboratories. J Clin Microbiol 48(3):900–907

    PubMed  PubMed Central  Google Scholar 

  55. Anhalt JP, Fenselau C (1975) Identification of bacteria using mass spectrometry. Anal Chem 47:219–225

    CAS  Google Scholar 

  56. Dubois D, Leyssene D, Chacornac JP, Kostrzewa M, Schmit PO, Talon R, Bonnet R, Delmas J (2010) Identification of a variety of Staphylococcus species by MALDI-TOF mass spectrometry. J Clin Microbiol 48:941–945

    PubMed  CAS  PubMed Central  Google Scholar 

  57. Ferreira L, Vega S, Sanchez-Juanes F, Gonzalez M, Herrero A, Muniz MC, Gonzalez-Buitrago JM, Munoz JL (2010) Identifying bacteria using a matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometer. Comparison with routine methods used in clinical microbiology laboratories. Enferm Infecc Microbiol Clin 28(8):492–497

    PubMed  Google Scholar 

  58. Bernardo K, Pakulat N, Macht M, Krut O, Seifert H, Fleer S, Hunger F, Kronke M (2002) Identification and discrimination of Staphylococcus aureus strains using matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Proteomics 2(6):747–753

    PubMed  CAS  Google Scholar 

  59. Friedrichs C, Rodloff AC, Chhatwal GS, Schellenberger W, Eschrich K (2007) Rapid identification of viridans streptococci by mass spectrometric discrimination. J Clin Microbiol 45(8):2392–2397

    PubMed  CAS  PubMed Central  Google Scholar 

  60. Degand N, Carbonnelle E, Dauphin B, Beretti JL, Le Bourgeois M, Sermet-Gaudelus I, Segonds C, Berche P, Nassif X, Ferroni A (2008) Matrix-assisted laser desorption ionization-time of flight mass spectrometry for identification of nonfermenting gram-negative bacilli isolated from cystic fibrosis patients. J Clin Microbiol 46(10):3361–3367

    PubMed  CAS  PubMed Central  Google Scholar 

  61. Nagy E, Becker S, Kostrzewa M, Barta N, Urban E (2012) The value of MALDI-TOF MS for the identification of clinically relevant anaerobic bacteria in routine laboratories. J Med Microbiol 61(Pt 10):1393–1400

    PubMed  CAS  Google Scholar 

  62. Knoester M, van Veen SQ, Claas EC, Kuijper EJ (2012) Routine identification of clinical isolates of anaerobic bacteria: matrix-assisted laser desorption ionization-time of flight mass spectrometry performs better than conventional identification methods. J Clin Microbiol 50(4):1504

    PubMed  CAS  PubMed Central  Google Scholar 

  63. Marklein G, Josten M, Klanke U, Muller E, Horre R, Maier T, Wenzel T, Kostrzewa M, Bierbaum G, Hoerauf A, Sahl HG (2009) Matrix-assisted laser desorption ionization-time of flight mass-spectrometry for fast and reliable identification of clinical yeast isolates. J Clin Microbiol 47(9):2912–2917

  64. Christner M, Rohde H, Wolters M, Sobottka I, Wegscheider K, Aepfelbacher M (2010) Rapid identification of bacteria from positive blood culture bottles by use of matrix-assisted laser desorption-ionization time of flight mass spectrometry fingerprinting. J Clin Microbiol 48(5):1584–1591

    PubMed  CAS  PubMed Central  Google Scholar 

  65. La Scola B, Raoult D (2009) Direct identification of bacteria in positive blood culture bottles by matrix-assisted laser desorption ionisation time-of-flight mass spectrometry. PLoS One 4(11):e8041

    PubMed  PubMed Central  Google Scholar 

  66. Prod’hom G, Bizzini A, Durussel C, Bille J, Greub G (2010) Matrix-assisted laser desorption ionization-time of flight mass spectrometry for direct bacterial identification from positive blood culture pellets. J Clin Microbiol 48(4):1481–1483

    PubMed  PubMed Central  Google Scholar 

  67. Ferreira L, Sanchez-Juanes F, Guerra IP, Garcia Garcia MI, Sanchez JE, Gonzalez-Buitrago JM, Bellido JL (2011) Microorganisms direct identification from blood culture by MALDI-TOF mass spectrometry. Clin Microbiol Infect 17(4):546–551

    PubMed  CAS  Google Scholar 

  68. Stevenson LG, Drake SK, Murray PR (2010) Rapid Identification of bacteria in positive blood culture broths by MALDI-TOF mass spectrometry. J Clin Microbiol 48(2):444–447

    PubMed  CAS  PubMed Central  Google Scholar 

  69. Loonen AJ, Jansz AR, Kreeftenberg H, Bruggeman CA, Wolffs PF, van den Brule AJ (2011) Acceleration of the direct identification of Staphylococcus aureus versus coagulase-negative staphylococci from blood culture material: a comparison of six bacterial DNA extraction methods. Eur J Clin Microbiol Infect Dis 30(3):337–342

    PubMed  CAS  PubMed Central  Google Scholar 

  70. Szabados F, Michels M, Kaase M, Gatermann S (2011) The sensitivity of direct identification from positive BacT/ALERT (bioMerieux) blood culture bottles by matrix-assisted laser desorption ionization time-of-flight mass spectrometry is low. Clin Microbiol Infect 17(2):192–195

    PubMed  CAS  Google Scholar 

  71. Drancourt M (2010) Detection of microorganisms in blood specimens using matrix-assisted laser desorption ionization time-of-flight mass spectrometry: a review. Clin Microbiol Infect 16(11):1620–1625

    PubMed  CAS  Google Scholar 

  72. Moussaoui W, Jaulhac B, Hoffmann AM, Ludes B, Kostrzewa M, Riegel P, Prevost G (2010) Matrix-assisted laser desorption ionization time-of-flight mass spectrometry identifies 90% of bacteria directly from blood culture vials. Clin Microbiol Infect 16(11):1631–1638

    PubMed  CAS  Google Scholar 

  73. Hrabak J, Studentova V, Walkova R, Zemlickova H, Jakubu V, Chudackova E, Gniadkowski M, Pfeifer Y, Perry JD, Wilkinson K, Bergerova T (2012) Detection of NDM-1, VIM-1, KPC, OXA-48, and OXA-162 carbapenemases by matrix-assisted laser desorption ionization-time of flight mass spectrometry. J Clin Microbiol 50(7):2441–2443

    PubMed  CAS  PubMed Central  Google Scholar 

  74. Sparbier K, Schubert S, Weller U, Boogen C, Kostrzewa M (2012) Matrix-assisted laser desorption ionization-time of flight mass spectrometry-based functional assay for rapid detection of resistance against beta-lactam antibiotics. J Clin Microbiol 50(3):927–937

    PubMed  CAS  PubMed Central  Google Scholar 

  75. Burckhardt I, Zimmermann S (2011) Using matrix-assisted laser desorption ionization-time of flight mass spectrometry to detect carbapenem resistance within 1 to 2.5 hours. J Clin Microbiol 49(9):3321–3324

    PubMed  CAS  PubMed Central  Google Scholar 

  76. Hrabak J, Chudackova E, Walkova R (2013) Matrix-assisted laser desorption ionization-time of flight (maldi-tof) mass spectrometry for detection of antibiotic resistance mechanisms: from research to routine diagnosis. Clin Microbiol Rev 26(1):103–114

    PubMed  CAS  PubMed Central  Google Scholar 

  77. Hartmann H, Stender H, Schafer A, Autenrieth IB, Kempf VA (2005) Rapid identification of Staphylococcus aureus in blood cultures by a combination of fluorescence in situ hybridization using peptide nucleic acid probes and flow cytometry. J Clin Microbiol 43(9):4855–4857

    PubMed  CAS  PubMed Central  Google Scholar 

  78. Wang P (2010) Simultaneous detection and differentiation of Staphylococcus species in blood cultures using fluorescence in situ hybridization. Med Princ Pract 19(3):218–221

    PubMed  Google Scholar 

  79. Gescher DM, Kovacevic D, Schmiedel D, Siemoneit S, Mallmann C, Halle E, Gobel UB, Moter A (2008) Fluorescence in situ hybridisation (FISH) accelerates identification of Gram-positive cocci in positive blood cultures. Int J Antimicrob Agents 32 Suppl 1:S51–9

  80. Jansen GJ, Mooibroek M, Idema J, Harmsen HJ, Welling GW, Degener JE (2000) Rapid identification of bacteria in blood cultures by using fluorescently labeled oligonucleotide probes. J Clin Microbiol 38(2):814–817

    PubMed  CAS  PubMed Central  Google Scholar 

  81. Sogaard M, Stender H, Schonheyder HC (2005) Direct identification of major blood culture pathogens, including Pseudomonas aeruginosa and Escherichia coli, by a panel of fluorescence in situ hybridization assays using peptide nucleic acid probes. J Clin Microbiol 43(4):1947–1949

    PubMed  CAS  PubMed Central  Google Scholar 

  82. Wellinghausen N, Nockler K, Sigge A, Bartel M, Essig A, Poppert S (2006) Rapid detection of Brucella spp. in blood cultures by fluorescence in situ hybridization. J Clin Microbiol 44(5):1828–1830

    PubMed  CAS  PubMed Central  Google Scholar 

  83. Kempf VA, Trebesius K, Autenrieth IB (2000) Fluorescent in situ hybridization allows rapid identification of microorganisms in blood cultures. J Clin Microbiol 38(2):830–838

    PubMed  CAS  PubMed Central  Google Scholar 

  84. Peters RP, van Agtmael MA, Simoons-Smit AM, Danner SA, Vandenbroucke-Grauls CM, Savelkoul PH (2006) Rapid identification of pathogens in blood cultures with a modified fluorescence in situ hybridization assay. J Clin Microbiol 44(11):4186–4188

    PubMed  CAS  PubMed Central  Google Scholar 

  85. Mullis KB, Faloona FA (1987) Specific synthesis of DNA in vitro via a polymerase-catalyzed chain reaction. Methods Enzymol 155:335–350

    PubMed  CAS  Google Scholar 

  86. Tissari P, Zumla A, Tarkka E, Mero S, Savolainen L, Vaara M, Aittakorpi A, Laakso S, Lindfors M, Piiparinen H, Maki M, Carder C, Huggett J, Gant V (2010) Accurate and rapid identification of bacterial species from positive blood cultures with a DNA-based microarray platform: an observational study. Lancet 375(9710):224–230

    PubMed  CAS  Google Scholar 

  87. Espy MJ, Uhl JR, Sloan LM, Buckwalter SP, Jones MF, Vetter EA, Yao JD, Wengenack NL, Rosenblatt JE, Cockerill FR 3rd, Smith TF (2006) Real-time PCR in clinical microbiology: applications for routine laboratory testing. Clin Microbiol Rev 19(1):165–256

    PubMed  CAS  PubMed Central  Google Scholar 

  88. Ieven M, Goossens H (1997) Relevance of nucleic acid amplification techniques for diagnosis of respiratory tract infections in the clinical laboratory. Clin Microbiol Rev 10(2):242–256

    PubMed  CAS  PubMed Central  Google Scholar 

  89. Persing DH (1993) Diagnostic molecular microbiology. Current challenges and future directions. Diagn Microbiol Infect Dis 16(2):159–163

    PubMed  CAS  Google Scholar 

  90. Greisen K, Loeffelholz M, Purohit A, Leong D (1994) PCR primers and probes for the 16S rRNA gene of most species of pathogenic bacteria, including bacteria found in cerebrospinal fluid. J Clin Microbiol 32(2):335–351

    PubMed  CAS  PubMed Central  Google Scholar 

  91. Jou NT, Yoshimori RB, Mason GR, Louie JS, Liebling MR (1997) Single-tube, nested, reverse transcriptase PCR for detection of viable Mycobacterium tuberculosis. J Clin Microbiol 35(5):1161–1165

    PubMed  CAS  PubMed Central  Google Scholar 

  92. Klausegger A, Hell M, Berger A, Zinober K, Baier S, Jones N, Sperl W, Kofler B (1999) Gram type-specific broad-range PCR amplification for rapid detection of 62 pathogenic bacteria. J Clin Microbiol 37(2):464–466

    PubMed  CAS  PubMed Central  Google Scholar 

  93. Van Burik JA, Myerson D, Schreckhise RW, Bowden RA (1998) Panfungal PCR assay for detection of fungal infection in human blood specimens. J Clin Microbiol 36(5):1169–1175

    PubMed  PubMed Central  Google Scholar 

  94. Brakstad OG, Aasbakk K, Maeland JA (1992) Detection of Staphylococcus aureus by polymerase chain reaction amplification of the nuc gene. J Clin Microbiol 30(7):1654–1660

    PubMed  CAS  PubMed Central  Google Scholar 

  95. Costa AM, Kay I, Palladino S (2005) Rapid detection of mecA and nuc genes in staphylococci by real-time multiplex polymerase chain reaction. Diagn Microbiol Infect Dis 51(1):13–17

    PubMed  CAS  Google Scholar 

  96. Iwase T, Hoshina S, Seki K, Shinji H, Masuda S, Mizunoe Y (2008) Rapid identification and specific quantification of Staphylococcus epidermidis by 5′ nuclease real-time polymerase chain reaction with a minor groove binder probe. Diagn Microbiol Infect Dis 60(2):217–219

    PubMed  CAS  Google Scholar 

  97. Martineau F, Picard FJ, Ke D, Paradis S, Roy PH, Ouellette M, Bergeron MG (2001) Development of a PCR assay for identification of staphylococci at genus and species levels. J Clin Microbiol 39(7):2541–2547

    PubMed  CAS  PubMed Central  Google Scholar 

  98. Prere MF, Baron O, Cohen Bacrie S, Fayet O (2006) Genotype MRSA, a new genetic test for the rapid identification of staphylococci and detection of mecA gene. Pathol Biol (Paris) 54(8–9):502–505

    CAS  Google Scholar 

  99. Wellinghausen N, Siegel D, Gebert S, Winter J (2009) Rapid detection of Staphylococcus aureus bacteremia and methicillin resistance by real-time PCR in whole blood samples. Eur J Clin Microbiol Infect Dis 28(8):1001–1005

    PubMed  CAS  Google Scholar 

  100. Hassan-King M, Baldeh I, Secka O, Falade A, Greenwood B (1994) Detection of Streptococcus pneumoniae DNA in blood cultures by PCR. J Clin Microbiol 32(7):1721–1724

    PubMed  CAS  PubMed Central  Google Scholar 

  101. Corless CE, Guiver M, Borrow R, Edwards-Jones V, Fox AJ, Kaczmarski EB (2001) Simultaneous detection of Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae in suspected cases of meningitis and septicemia using real-time PCR. J Clin Microbiol 39(4):1553–1558

    PubMed  CAS  PubMed Central  Google Scholar 

  102. Peters RP, van Agtmael MA, Gierveld S, Danner SA, Groeneveld AB, Vandenbroucke-Grauls CM, Savelkoul PH (2007) Quantitative detection of Staphylococcus aureus and Enterococcus faecalis DNA in blood to diagnose bacteremia in patients in the intensive care unit. J Clin Microbiol 45(11):3641–3646

    PubMed  CAS  PubMed Central  Google Scholar 

  103. Loeffler J, Hebart H, Cox P, Flues N, Schumacher U, Einsele H (2001) Nucleic acid sequence-based amplification of Aspergillus RNA in blood samples. J Clin Microbiol 39(4):1626–1629

    PubMed  CAS  PubMed Central  Google Scholar 

  104. Wellinghausen N, Siegel D, Winter J, Gebert S (2009) Rapid diagnosis of candidaemia by real-time PCR detection of Candida DNA in blood samples. J Med Microbiol 58(Pt 8):1106–1111

    PubMed  CAS  Google Scholar 

  105. Mancini N, Carletti S, Ghidoli N, Cichero P, Burioni R, Clementi M (2010) The era of molecular and other non-culture-based methods in diagnosis of sepsis. Clin Microbiol Rev 23(1):235–251

    PubMed  CAS  PubMed Central  Google Scholar 

  106. Dierkes C, Ehrenstein B, Siebig S, Linde HJ, Reischl U, Salzberger B (2009) Clinical impact of a commercially available multiplex PCR system for rapid detection of pathogens in patients with presumed sepsis. BMC Infect Dis 9:126

    PubMed  PubMed Central  Google Scholar 

  107. Hansen WL, Beuving J, Bruggeman CA, Wolffs PF (2010) Molecular probes for diagnosis of clinically relevant bacterial infections in blood cultures. J Clin Microbiol 48(12):4432–4438

    PubMed  CAS  PubMed Central  Google Scholar 

  108. Barken KB, Haagensen JA, Tolker-Nielsen T (2007) Advances in nucleic acid-based diagnostics of bacterial infections. Clin Chim Acta 384(1–2):1–11

    PubMed  CAS  Google Scholar 

  109. Fredricks DN, Relman DA (1998) Improved amplification of microbial DNA from blood cultures by removal of the PCR inhibitor sodium polyanetholesulfonate. J Clin Microbiol 36(10):2810–2816

    PubMed  CAS  PubMed Central  Google Scholar 

  110. Klouche M, Schroder U (2008) Rapid methods for diagnosis of bloodstream infections. Clin Chem Lab Med 46(7):888–908

    PubMed  CAS  Google Scholar 

  111. Song JH, Cho H, Park MY, Na DS, Moon HB, Pai CH (1993) Detection of Salmonella typhi in the blood of patients with typhoid fever by polymerase chain reaction. J Clin Microbiol 31(6):1439–1443

    PubMed  CAS  PubMed Central  Google Scholar 

  112. Iralu JV, Sritharan VK, Pieciak WS, Wirth DF, Maguire JH, Barker RH Jr (1993) Diagnosis of Mycobacterium avium bacteremia by polymerase chain reaction. J Clin Microbiol 31(7):1811–1814

    PubMed  CAS  PubMed Central  Google Scholar 

  113. Rantakokko-Jalava K, Jalava J (2002) Optimal DNA isolation method for detection of bacteria in clinical specimens by broad-range PCR. J Clin Microbiol 40(11):4211–4217

    PubMed  CAS  PubMed Central  Google Scholar 

  114. Handschur M, Karlic H, Hertel C, Pfeilstocker M, Haslberger AG (2008) Preanalytic removal of human DNA eliminates false signals in general 16S rDNA PCR monitoring of bacterial pathogens in blood. Comp Immunol Microbiol Infect Dis 32(3):207–219

  115. Al-Soud WA, Radstrom P (2001) Purification and characterization of PCR-inhibitory components in blood cells. J Clin Microbiol 39(2):485–493

    PubMed  CAS  PubMed Central  Google Scholar 

  116. Muhl H, Kochem AJ, Disque C, Sakka SG (2010) Activity and DNA contamination of commercial polymerase chain reaction reagents for the universal 16S rDNA real-time polymerase chain reaction detection of bacterial pathogens in blood. Diagn Microbiol Infect Dis 66(1):41–49

    PubMed  Google Scholar 

  117. Corless CE, Guiver M, Borrow R, Edwards-Jones V, Kaczmarski EB, Fox AJ (2000) Contamination and sensitivity issues with a real-time universal 16S rRNA PCR. J Clin Microbiol 38(5):1747–1752

    PubMed  CAS  PubMed Central  Google Scholar 

  118. Horz HP, Scheer S, Huenger F, Vianna ME, Conrads G (2008) Selective isolation of bacterial DNA from human clinical specimens. J Microbiol Methods 72(1):98–102

    PubMed  CAS  Google Scholar 

  119. Horz HP, Scheer S, Vianna ME, Conrads G (2010) New methods for selective isolation of bacterial DNA from human clinical specimens. Anaerobe 16(1):47–53

    PubMed  CAS  Google Scholar 

  120. Loonen AJ, Bos MP, van Meerbergen B, Neerken S, Catsburg A, Dobbelaer I, Penterman R, Maertens G, van de Wiel P, Savelkoul P, van den Brule AJ (2013) Comparison of pathogen DNA isolation methods from large volumes of whole blood to improve molecular diagnosis of bloodstream infections. PLoS One 8(8):e72349

    PubMed  CAS  PubMed Central  Google Scholar 

  121. Hansen WL, Bruggeman CA, Wolffs PF (2009) Evaluation of new preanalysis sample treatment tools and DNA isolation protocols to improve bacterial pathogen detection in whole blood. J Clin Microbiol 47(8):2629–2631

    PubMed  PubMed Central  Google Scholar 

  122. Wiesinger-Mayr H, Jordana-Lluch E, Martro E, Schoenthaler S, Noehammer C (2011) Establishment of a semi-automated pathogen DNA isolation from whole blood and comparison with commercially available kits. J Microbiol Methods 85(3):206–213

    PubMed  CAS  Google Scholar 

  123. Gebert S, Siegel D, Wellinghausen N (2008) Rapid detection of pathogens in blood culture bottles by real-time PCR in conjunction with the pre-analytic tool MolYsis. J Infect 57:307–316

    PubMed  Google Scholar 

  124. Casalta JP, Gouriet F, Roux V, Thuny F, Habib G, Raoult D (2009) Evaluation of the LightCycler(R) SeptiFast test in the rapid etiologic diagnostic of infectious endocarditis. Eur J Clin Microbiol Infect Dis 28(6):569–573

    PubMed  CAS  Google Scholar 

  125. Mauro MV, Cavalcanti P, Perugini D, Noto A, Sperli D, Giraldi C (2012) Diagnostic utility of LightCycler SeptiFast and procalcitonin assays in the diagnosis of bloodstream infection in immunocompromised patients. Diagn Microbiol Infect Dis 73(4):308–311

    PubMed  CAS  Google Scholar 

  126. Kuhn C, Disque C, Muhl H, Orszag P, Stiesch M, Haverich A (2011) Evaluation of commercial universal rRNA gene PCR plus sequencing tests for identification of bacteria and fungi associated with infectious endocarditis. J Clin Microbiol 49(8):2919–2923

    PubMed  PubMed Central  Google Scholar 

  127. Wellinghausen N, Kochem AJ, Disque C, Muhl H, Gebert S, Winter J, Matten J, Sakka SG (2009) Diagnosis of bacteremia in whole-blood samples by use of a commercial universal 16S rRNA gene-based PCR and sequence analysis. J Clin Microbiol 47(9):2759–2765

    PubMed  CAS  PubMed Central  Google Scholar 

  128. Fitting C, Parlato M, Adib-Conquy M, Memain N, Philippart F, Misset B, Monchi M, Cavaillon JM, Adrie C (2012) DNAemia detection by multiplex PCR and biomarkers for infection in systemic inflammatory response syndrome patients. PLoS One 7(6):e38916

    PubMed  CAS  PubMed Central  Google Scholar 

  129. Serra J, Rosello E, Figueras C, Pujol M, Peña M, Céspedes P, Dapena JL, Díaz-Heredia C, Codina MG, Andreu A (2012) Clinical evaluation of the Magicplex Sepsis Real-time Test (Seegene) to detect Candida DNA in pediatric patients. Crit Care 16:21

    Google Scholar 

  130. Schreiber J, Nierhaus A, Braune SA, de Heer G, Kluge S (2013) Comparison of three different commercial PCR assays for the detection of pathogens in critically ill sepsis patients. Med Klin Intensivmed Notfallmed 108(4):311–318

    CAS  Google Scholar 

  131. Loonen AJ, de Jager CP, Tosserams J, Kusters R, Hilbink M, Wever PC, van den Brule AJ (2014) Biomarkers and molecular analysis to improve bloodstream infection diagnostics in an emergency care unit. PLoS One 9(1):e87315

    PubMed  PubMed Central  Google Scholar 

  132. Oliver JD (2005) The viable but nonculturable state in bacteria. J Microbiol 43:93–100

    PubMed  Google Scholar 

  133. Birch L, Dawson CE, Cornett JH, Keer JT (2001) A comparison of nucleic acid amplification techniques for the assessment of bacterial viability. Lett Appl Microbiol 33(4):296–301

    PubMed  CAS  Google Scholar 

  134. Aellen S, Que YA, Guignard B, Haenni M, Moreillon P (2006) Detection of live and antibiotic-killed bacteria by quantitative real-time PCR of specific fragments of rRNA. Antimicrob Agents Chemother 50(6):1913–1920

    PubMed  CAS  PubMed Central  Google Scholar 

  135. Morre SA, Sillekens PT, Jacobs MV, de Blok S, Ossewaarde JM, van Aarle P, van Gemen B, Walboomers JM, Meijer CJ, van den Brule AJ (1998) Monitoring of Chlamydia trachomatis infections after antibiotic treatment using RNA detection by nucleic acid sequence based amplification. Mol Pathol 51(3):149–154

    PubMed  CAS  PubMed Central  Google Scholar 

  136. Lindahl T (1993) Instability and decay of the primary structure of DNA. Nature 362(6422):709–715

    PubMed  CAS  Google Scholar 

  137. Chuang YC, Chang SC, Wang WK (2012) Using the rate of bacterial clearance determined by real-time polymerase chain reaction as a timely surrogate marker to evaluate the appropriateness of antibiotic usage in critical patients with Acinetobacter baumannii bacteremia. Crit Care Med 40(8):2273–2280

    PubMed  CAS  Google Scholar 

  138. Sakka SG, Kochem AJ, Disque C, Wellinghausen N (2009) Blood infection diagnosis by 16S rDNA broad-spectrum polymerase chain reaction: the relationship between antibiotic treatment and bacterial DNA load. Anesth Analg 109(5):1707–1708

    PubMed  Google Scholar 

  139. Peters RP, de Boer RF, Schuurman T, Gierveld S, Kooistra-Smid M, van Agtmael MA, Vandenbroucke-Grauls CM, Persoons MC, Savelkoul PH (2009) Streptococcus pneumoniae DNA load in blood as a marker of infection in patients with community-acquired pneumonia. J Clin Microbiol 47(10):3308–3312

    PubMed  CAS  PubMed Central  Google Scholar 

  140. Nocker A, Sossa-Fernandez P, Burr MD, Camper AK (2007) Use of propidium monoazide for live/dead distinction in microbial ecology. Appl Environ Microbiol 73(16):5111–5117

    PubMed  CAS  PubMed Central  Google Scholar 

  141. Josephson KL, Gerba CP, Pepper IL (1993) Polymerase chain reaction detection of nonviable bacterial pathogens. Appl Environ Microbiol 59(10):3513–3515

    PubMed  CAS  PubMed Central  Google Scholar 

  142. Sheridan GE, Masters CI, Shallcross JA, MacKey BM (1998) Detection of mRNA by reverse transcription-PCR as an indicator of viability in Escherichia coli cells. Appl Environ Microbiol 64(4):1313–1318

    PubMed  CAS  PubMed Central  Google Scholar 

  143. Hellyer TJ, DesJardin LE, Teixeira L, Perkins MD, Cave MD, Eisenach KD (1999) Detection of viable Mycobacterium tuberculosis by reverse transcriptase-strand displacement amplification of mRNA. J Clin Microbiol 37(3):518–523

    PubMed  CAS  PubMed Central  Google Scholar 

  144. Cenciarini C, Courtois S, Raoult D, La Scola B (2008) Influence of long time storage in mineral water on RNA stability of Pseudomonas aeruginosa and Escherichia coli after heat inactivation. PLoS One 3(10):e3443

    PubMed  PubMed Central  Google Scholar 

  145. Kaleta EJ, Clark AE, Johnson DR, Gamage DC, Wysocki VH, Cherkaoui A, Schrenzel J, Wolk DM (2011) Use of PCR coupled with electrospray ionization mass spectrometry for rapid identification of bacterial and yeast bloodstream pathogens from blood culture bottles. J Clin Microbiol 49(1):345–353

    PubMed  CAS  PubMed Central  Google Scholar 

  146. Kaleta EJ, Clark AE, Cherkaoui A, Wysocki VH, Ingram EL, Schrenzel J, Wolk DM (2011) Comparative analysis of PCR-electrospray ionization/mass spectrometry (MS) and MALDI-TOF/MS for the identification of bacteria and yeast from positive blood culture bottles. Clin Chem 57(7):1057–1067

    PubMed  CAS  Google Scholar 

  147. Gharizadeh B, Norberg E, Loffler J, Jalal S, Tollemar J, Einsele H, Klingspor L, Nyren P (2004) Identification of medically important fungi by the Pyrosequencing technology. Mycoses 47(1–2):29–33

    PubMed  CAS  Google Scholar 

  148. Jordan JA, Butchko AR, Durso MB (2005) Use of pyrosequencing of 16S rRNA fragments to differentiate between bacteria responsible for neonatal sepsis. J Mol Diagn 7(1):105–110

    PubMed  CAS  PubMed Central  Google Scholar 

  149. Jordan JA, Jones-Laughner J, Durso MB (2009) Utility of pyrosequencing in identifying bacteria directly from positive blood culture bottles. J Clin Microbiol 47(2):368–372

    PubMed  CAS  PubMed Central  Google Scholar 

  150. van Vliet AH (2010) Next generation sequencing of microbial transcriptomes: challenges and opportunities. FEMS Microbiol Lett 302(1):1–7

    PubMed  Google Scholar 

  151. Koser CU, Holden MT, Ellington MJ, Cartwright EJ, Brown NM, Ogilvy-Stuart AL, Hsu LY, Chewapreecha C, Croucher NJ, Harris SR, Sanders M, Enright MC, Dougan G, Bentley SD, Parkhill J, Fraser LJ, Betley JR, Schulz-Trieglaff OB, Smith GP, Peacock SJ (2012) Rapid whole-genome sequencing for investigation of a neonatal MRSA outbreak. N Engl J Med 366(24):2267–2275

    PubMed  CAS  PubMed Central  Google Scholar 

  152. Salipante SJ, Sengupta DJ, Rosenthal C, Costa G, Spangler J, Sims EH, Jacobs MA, Miller SI, Hoogestraat DR, Cookson BT, McCoy C, Matsen FA, Shendure J, Lee CC, Harkins TT, Hoffman NG (2013) Rapid 16S rRNA next-generation sequencing of polymicrobial clinical samples for diagnosis of complex bacterial infections. PLoS One 8(5):e65226

    PubMed  CAS  PubMed Central  Google Scholar 

  153. Cheval J, Sauvage V, Frangeul L, Dacheux L, Guigon G, Dumey N, Pariente K, Rousseaux C, Dorange F, Berthet N, Brisse S, Moszer I, Bourhy H, Manuguerra CJ, Lecuit M, Burguiere A, Caro V, Eloit M (2011) Evaluation of high-throughput sequencing for identifying known and unknown viruses in biological samples. J Clin Microbiol 49(9):3268–3275

    PubMed  CAS  PubMed Central  Google Scholar 

  154. Frey KG, Herrera-Galeano JE, Redden CL, Luu TV, Servetas SL, Mateczun AJ, Mokashi VP, Bishop-Lilly KA (2014) Comparison of three next-generation sequencing platforms for metagenomic sequencing and identification of pathogens in blood. BMC Genomics 15:96

    PubMed  PubMed Central  Google Scholar 

  155. Dalton WS, Friend SH (2006) Cancer biomarkers—an invitation to the table. Science 312(5777):1165–1168

    PubMed  CAS  Google Scholar 

  156. Petrikkos GL, Christofilopoulou SA, Tentolouris NK, Charvalos EA, Kosmidis CJ, Daikos GL (2005) Value of measuring serum procalcitonin, C-reactive protein, and mannan antigens to distinguish fungal from bacterial infections. Eur J Clin Microbiol Infect Dis 24(4):272–275

    PubMed  CAS  Google Scholar 

  157. Standage SW, Wong HR (2011) Biomarkers for pediatric sepsis and septic shock. Expert Rev Anti-Infect Ther 9(1):71–79

    PubMed  CAS  PubMed Central  Google Scholar 

  158. Uusitalo-Seppala R, Koskinen P, Leino A, Peuravuori H, Vahlberg T, Rintala EM (2011) Early detection of severe sepsis in the emergency room: diagnostic value of plasma C-reactive protein, procalcitonin, and interleukin-6. Scand J Infect Dis 43(11–12):883–890

    PubMed  Google Scholar 

  159. Mencacci A, Leli C, Cardaccia A, Meucci M, Moretti A, D’Alo F, Farinelli S, Pagliochini R, Barcaccia M, Bistoni F (2012) Procalcitonin predicts real-time PCR results in blood samples from patients with suspected sepsis. PLoS One 7(12):e53279

    PubMed  CAS  PubMed Central  Google Scholar 

  160. de Jager CP, van Wijk PT, Mathoera RB, de Jongh-Leuvenink J, van der Poll T, Wever PC (2010) Lymphocytopenia and neutrophil-lymphocyte count ratio predict bacteremia better than conventional infection markers in an emergency care unit. Crit Care 14(5):R192

    PubMed  PubMed Central  Google Scholar 

  161. Backes Y, van der Sluijs KF, Mackie DP, Tacke F, Koch A, Tenhunen JJ, Schultz MJ (2012) Usefulness of suPAR as a biological marker in patients with systemic inflammation or infection: a systematic review. Intensive Care Med 38(9):1418–1428

    PubMed  CAS  PubMed Central  Google Scholar 

  162. Donadello K, Scolletta S, Covajes C, Vincent JL (2012) suPAR as a prognostic biomarker in sepsis. BMC Med 10:2

    PubMed  CAS  PubMed Central  Google Scholar 

  163. Haupt TH, Petersen J, Ellekilde G, Klausen HH, Thorball CW, Eugen-Olsen J, Andersen O (2012) Plasma suPAR levels are associated with mortality, admission time, and Charlson Comorbidity Index in the acutely admitted medical patient: a prospective observational study. Crit Care 16(4):R130

    PubMed  PubMed Central  Google Scholar 

  164. Hoenigl M, Raggam RB, Wagner J, Valentin T, Leitner E, Seeber K, Zollner-Schwetz I, Krammer W, Pruller F, Grisold AJ, Krause R (2013) Diagnostic accuracy of soluble urokinase plasminogen activator receptor (suPAR) for prediction of bacteremia in patients with systemic inflammatory response syndrome. Clin Biochem 46(3):225–229

    PubMed  CAS  Google Scholar 

  165. Koch A, Voigt S, Kruschinski C, Sanson E, Duckers H, Horn A, Yagmur E, Zimmermann H, Trautwein C, Tacke F (2011) Circulating soluble urokinase plasminogen activator receptor is stably elevated during the first week of treatment in the intensive care unit and predicts mortality in critically ill patients. Crit Care 15(1):R63

    PubMed  PubMed Central  Google Scholar 

  166. Meisner M, Tschaikowsky K, Palmaers T, Schmidt J (1999) Comparison of procalcitonin (PCT) and C-reactive protein (CRP) plasma concentrations at different SOFA scores during the course of sepsis and MODS. Crit Care 3(1):45–50

    PubMed  PubMed Central  Google Scholar 

  167. Silvestre J, Coelho L, Povoa P (2010) Should C-reactive protein concentration at ICU discharge be used as a prognostic marker? BMC Anesthesiol 10:17

    PubMed  PubMed Central  Google Scholar 

  168. Gogos CA, Drosou E, Bassaris HP, Skoutelis A (2000) Pro- versus anti-inflammatory cytokine profile in patients with severe sepsis: a marker for prognosis and future therapeutic options. J Infect Dis 181(1):176–180

    PubMed  CAS  Google Scholar 

  169. Simon L, Gauvin F, Amre DK, Saint-Louis P, Lacroix J (2004) Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis. Clin Infect Dis 39(2):206–217

    PubMed  CAS  Google Scholar 

  170. Tang BM, Eslick GD, Craig JC, McLean AS (2007) Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis. Lancet Infect Dis 7(3):210–217

    PubMed  CAS  Google Scholar 

  171. Uzzan B, Cohen R, Nicolas P, Cucherat M, Perret GY (2006) 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 34(7):1996–2003

    PubMed  CAS  Google Scholar 

  172. Reinhart K, Bauer M, Riedemann NC, Hartog CS (2012) New approaches to sepsis: molecular diagnostics and biomarkers. Clin Microbiol Rev 25(4):609–634

    PubMed  CAS  PubMed Central  Google Scholar 

  173. Zahorec R (2001) Ratio of neutrophil to lymphocyte counts—rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl Lek Listy 102(1):5–14

    PubMed  CAS  Google Scholar 

  174. Roldan AL, Cubellis MV, Masucci MT, Behrendt N, Lund LR, Dano K, Appella E, Blasi F (1990) Cloning and expression of the receptor for human urokinase plasminogen activator, a central molecule in cell surface, plasmin dependent proteolysis. EMBO J 9(2):467–474

    PubMed  CAS  PubMed Central  Google Scholar 

  175. Ploug M, Ronne E, Behrendt N, Jensen AL, Blasi F, Dano K (1991) Cellular receptor for urokinase plasminogen activator. Carboxyl-terminal processing and membrane anchoring by glycosyl-phosphatidylinositol. J Biol Chem 266(3):1926–1933

    PubMed  CAS  Google Scholar 

  176. Eugen-Olsen J (2011) suPAR—a future risk marker in bacteremia. J Intern Med 270(1):29–31

    PubMed  CAS  Google Scholar 

  177. Thuno M, Macho B, Eugen-Olsen J (2009) suPAR: the molecular crystal ball. Dis Markers 27(3):157–172

    PubMed  PubMed Central  Google Scholar 

  178. Mizukami IF, Faulkner NE, Gyetko MR, Sitrin RG, Todd RF 3rd (1995) Enzyme-linked immunoabsorbent assay detection of a soluble form of urokinase plasminogen activator receptor in vivo. Blood 86(1):203–211

    PubMed  CAS  Google Scholar 

  179. Koch A, Tacke F (2012) Risk stratification and triage in the emergency department: has this become ‘suPAR’ easy? J Intern Med 272(3):243–246

    PubMed  CAS  Google Scholar 

  180. Call DR, Bakko MK, Krug MJ, Roberts MC (2003) Identifying antimicrobial resistance genes with DNA microarrays. Antimicrob Agents Chemother 47(10):3290–3295

    PubMed  CAS  PubMed Central  Google Scholar 

  181. Perreten V, Vorlet-Fawer L, Slickers P, Ehricht R, Kuhnert P, Frey J (2005) Microarray-based detection of 90 antibiotic resistance genes of gram-positive bacteria. J Clin Microbiol 43(5):2291–2302

    PubMed  CAS  PubMed Central  Google Scholar 

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  1. Laboratory for Molecular Diagnostics, Department of Medical Microbiology and Pathology, Jeroen Bosch Hospital, ‘s-Hertogenbosch, The Netherlands

    A. J. M. Loonen & A. J. C. van den Brule

  2. Department of Medical Microbiology, Maastricht University Medical Centre, CAPHRI, Maastricht, The Netherlands

    A. J. M. Loonen, P. F. G. Wolffs & C. A. Bruggeman

  3. Department of Medical Molecular Diagnostics, Fontys University of Applied Sciences, Eindhoven, The Netherlands

    A. J. M. Loonen & A. J. C. van den Brule

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Loonen, A.J.M., Wolffs, P.F.G., Bruggeman, C.A. et al. Developments for improved diagnosis of bacterial bloodstream infections. Eur J Clin Microbiol Infect Dis 33, 1687–1702 (2014). https://doi.org/10.1007/s10096-014-2153-4

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