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Erschienen in: European Journal of Clinical Microbiology & Infectious Diseases 10/2014

01.10.2014 | Review

Developments for improved diagnosis of bacterial bloodstream infections

verfasst von: A. J. M. Loonen, P. F. G. Wolffs, C. A. Bruggeman, A. J. C. van den Brule

Erschienen in: European Journal of Clinical Microbiology & Infectious Diseases | Ausgabe 10/2014

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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.
Literatur
1.
Zurück zum Zitat Libman E (1897) Weitere Mitteilungen über die Streptokokken-enteritis bei Säuglingen. Zentralbl Bakteriol XXII:376 Libman E (1897) Weitere Mitteilungen über die Streptokokken-enteritis bei Säuglingen. Zentralbl Bakteriol XXII:376
2.
Zurück zum Zitat Institute CaLS (2007) Principles and procedures for blood cultures; approved guidline. CLSI Document M47-A (ISBN 1-56238-641-7) Institute CaLS (2007) Principles and procedures for blood cultures; approved guidline. CLSI Document M47-A (ISBN 1-56238-641-7)
3.
Zurück zum Zitat 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):1237–1248PubMed 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):1237–1248PubMed
4.
Zurück zum Zitat Lim SM, Webb SA (2005) Nosocomial bacterial infections in intensive care units. I: organisms and mechanisms of antibiotic resistance. Anaesthesia 60(9):887–902PubMed Lim SM, Webb SA (2005) Nosocomial bacterial infections in intensive care units. I: organisms and mechanisms of antibiotic resistance. Anaesthesia 60(9):887–902PubMed
5.
Zurück zum Zitat 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):3520–3523PubMedPubMedCentral 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):3520–3523PubMedPubMedCentral
6.
Zurück zum Zitat Spraycar M (1995) Stedman’s Medical Dictionary. Williams & Wilkins, Baltimore, MD Spraycar M (1995) Stedman’s Medical Dictionary. Williams & Wilkins, Baltimore, MD
7.
Zurück zum Zitat 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):584–602PubMed 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):584–602PubMed
8.
Zurück zum Zitat 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):1644–1655PubMed 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):1644–1655PubMed
9.
Zurück zum Zitat 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):1250–1256PubMed 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):1250–1256PubMed
11.
Zurück zum Zitat 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):76–83PubMed 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):76–83PubMed
12.
Zurück zum Zitat 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–R162PubMedPubMedCentral 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–R162PubMedPubMedCentral
13.
Zurück zum Zitat CDC (1992) Report of mortality statistics. Mon Vital Stat Rep 40(11):1–23 CDC (1992) Report of mortality statistics. Mon Vital Stat Rep 40(11):1–23
14.
Zurück zum Zitat 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):606–618PubMed 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):606–618PubMed
15.
Zurück zum Zitat 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):108–121PubMed 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):108–121PubMed
16.
Zurück zum Zitat Angus DC, Wax RS (2001) Epidemiology of sepsis: an update. Crit Care Med 29(7 Suppl):S109–S116PubMed Angus DC, Wax RS (2001) Epidemiology of sepsis: an update. Crit Care Med 29(7 Suppl):S109–S116PubMed
17.
Zurück zum Zitat 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):1118–1126PubMed 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):1118–1126PubMed
18.
Zurück zum Zitat 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):616–620PubMed 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):616–620PubMed
19.
Zurück zum Zitat 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):309–317PubMed 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):309–317PubMed
20.
Zurück zum Zitat Annane D, Bellissant E, Cavaillon JM (2005) Septic shock. Lancet 365(9453):63–78PubMed Annane D, Bellissant E, Cavaillon JM (2005) Septic shock. Lancet 365(9453):63–78PubMed
21.
Zurück zum Zitat Shoham S, Marwaha S (2010) Invasive fungal infections in the ICU. J Intensive Care Med 25(2):78–92PubMed Shoham S, Marwaha S (2010) Invasive fungal infections in the ICU. J Intensive Care Med 25(2):78–92PubMed
22.
Zurück zum Zitat 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):949–958PubMed 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):949–958PubMed
23.
Zurück zum Zitat Mermel LA, Maki DG (1993) Detection of bacteremia in adults: consequences of culturing an inadequate volume of blood. Ann Intern Med 119(4):270–272PubMed Mermel LA, Maki DG (1993) Detection of bacteremia in adults: consequences of culturing an inadequate volume of blood. Ann Intern Med 119(4):270–272PubMed
25.
Zurück zum Zitat 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):595–601PubMed 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):595–601PubMed
26.
Zurück zum Zitat 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):317–318PubMed 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):317–318PubMed
27.
Zurück zum Zitat 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):2765–2769PubMedPubMedCentral 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):2765–2769PubMedPubMedCentral
28.
Zurück zum Zitat 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):1724–1730PubMed 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):1724–1730PubMed
29.
Zurück zum Zitat 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):3482–3485PubMedPubMedCentral 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):3482–3485PubMedPubMedCentral
30.
Zurück zum Zitat Hall MM, Ilstrup DM, Washington JA 2nd (1976) Effect of volume of blood cultured on detection of bacteremia. J Clin Microbiol 3(6):643–645PubMedPubMedCentral Hall MM, Ilstrup DM, Washington JA 2nd (1976) Effect of volume of blood cultured on detection of bacteremia. J Clin Microbiol 3(6):643–645PubMedPubMedCentral
31.
Zurück zum Zitat 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):558–561PubMedPubMedCentral 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):558–561PubMedPubMedCentral
32.
Zurück zum Zitat 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):1615–1624PubMed 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):1615–1624PubMed
33.
Zurück zum Zitat 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):529–535PubMed 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):529–535PubMed
34.
Zurück zum Zitat 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):46–51PubMed 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):46–51PubMed
35.
Zurück zum Zitat 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):798–805PubMed 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):798–805PubMed
36.
Zurück zum Zitat 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):860–868PubMed 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):860–868PubMed
37.
Zurück zum Zitat 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):2181–2185PubMedPubMedCentral 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):2181–2185PubMedPubMedCentral
38.
Zurück zum Zitat 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):774–781PubMed 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):774–781PubMed
39.
Zurück zum Zitat 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):2180–2184PubMedPubMedCentral 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):2180–2184PubMedPubMedCentral
40.
Zurück zum Zitat 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):978–981PubMedPubMedCentral 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):978–981PubMedPubMedCentral
41.
Zurück zum Zitat 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):193–196PubMed 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):193–196PubMed
42.
Zurück zum Zitat 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):1245–1249PubMedPubMedCentral 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):1245–1249PubMedPubMedCentral
43.
Zurück zum Zitat 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):2691–2694PubMedPubMedCentral 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):2691–2694PubMedPubMedCentral
44.
Zurück zum Zitat Piette A, Verschraegen G (2009) Role of coagulase-negative staphylococci in human disease. Vet Microbiol 134(1–2):45–54PubMed Piette A, Verschraegen G (2009) Role of coagulase-negative staphylococci in human disease. Vet Microbiol 134(1–2):45–54PubMed
45.
Zurück zum Zitat Bates DW, Lee TH (1992) Rapid classification of positive blood cultures. Prospective validation of a multivariate algorithm. JAMA 267(14):1962–1966PubMed Bates DW, Lee TH (1992) Rapid classification of positive blood cultures. Prospective validation of a multivariate algorithm. JAMA 267(14):1962–1966PubMed
46.
47.
Zurück zum Zitat 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 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
48.
Zurück zum Zitat 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):563–565PubMedPubMedCentral 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):563–565PubMedPubMedCentral
49.
Zurück zum Zitat 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):1775–1779PubMed 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):1775–1779PubMed
50.
Zurück zum Zitat 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):208–212PubMed 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):208–212PubMed
51.
Zurück zum Zitat 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):1651–1655PubMed 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):1651–1655PubMed
52.
Zurück zum Zitat McKenzie R, Reimer LG (1987) Effect of antimicrobials on blood cultures in endocarditis. Diagn Microbiol Infect Dis 8(3):165–172PubMed McKenzie R, Reimer LG (1987) Effect of antimicrobials on blood cultures in endocarditis. Diagn Microbiol Infect Dis 8(3):165–172PubMed
53.
Zurück zum Zitat Zadoks RN, Watts JL (2009) Species identification of coagulase-negative staphylococci: genotyping is superior to phenotyping. Vet Microbiol 134(1–2):20–28PubMed Zadoks RN, Watts JL (2009) Species identification of coagulase-negative staphylococci: genotyping is superior to phenotyping. Vet Microbiol 134(1–2):20–28PubMed
54.
Zurück zum Zitat 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):900–907PubMedPubMedCentral 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):900–907PubMedPubMedCentral
55.
Zurück zum Zitat Anhalt JP, Fenselau C (1975) Identification of bacteria using mass spectrometry. Anal Chem 47:219–225 Anhalt JP, Fenselau C (1975) Identification of bacteria using mass spectrometry. Anal Chem 47:219–225
56.
Zurück zum Zitat 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 48:941–945PubMedPubMedCentral 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 48:941–945PubMedPubMedCentral
57.
Zurück zum Zitat 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):492–497PubMed 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):492–497PubMed
58.
Zurück zum Zitat 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):747–753PubMed 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):747–753PubMed
59.
Zurück zum Zitat 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):2392–2397PubMedPubMedCentral 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):2392–2397PubMedPubMedCentral
60.
Zurück zum Zitat 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):3361–3367PubMedPubMedCentral 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):3361–3367PubMedPubMedCentral
61.
Zurück zum Zitat 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):1393–1400PubMed 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):1393–1400PubMed
62.
Zurück zum Zitat 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):1504PubMedPubMedCentral 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):1504PubMedPubMedCentral
63.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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):1584–1591PubMedPubMedCentral 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):1584–1591PubMedPubMedCentral
65.
Zurück zum Zitat 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):e8041PubMedPubMedCentral 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):e8041PubMedPubMedCentral
66.
Zurück zum Zitat 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):1481–1483PubMedPubMedCentral 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):1481–1483PubMedPubMedCentral
67.
Zurück zum Zitat 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):546–551PubMed 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):546–551PubMed
68.
Zurück zum Zitat 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):444–447PubMedPubMedCentral 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):444–447PubMedPubMedCentral
69.
Zurück zum Zitat 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):337–342PubMedPubMedCentral 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):337–342PubMedPubMedCentral
70.
Zurück zum Zitat 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):192–195PubMed 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):192–195PubMed
71.
Zurück zum Zitat 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):1620–1625PubMed 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):1620–1625PubMed
72.
Zurück zum Zitat 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):1631–1638PubMed 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):1631–1638PubMed
73.
Zurück zum Zitat 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):2441–2443PubMedPubMedCentral 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):2441–2443PubMedPubMedCentral
74.
Zurück zum Zitat 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):927–937PubMedPubMedCentral 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):927–937PubMedPubMedCentral
75.
Zurück zum Zitat 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):3321–3324PubMedPubMedCentral 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):3321–3324PubMedPubMedCentral
76.
Zurück zum Zitat 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):103–114PubMedPubMedCentral 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):103–114PubMedPubMedCentral
77.
Zurück zum Zitat 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):4855–4857PubMedPubMedCentral 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):4855–4857PubMedPubMedCentral
78.
Zurück zum Zitat Wang P (2010) Simultaneous detection and differentiation of Staphylococcus species in blood cultures using fluorescence in situ hybridization. Med Princ Pract 19(3):218–221PubMed Wang P (2010) Simultaneous detection and differentiation of Staphylococcus species in blood cultures using fluorescence in situ hybridization. Med Princ Pract 19(3):218–221PubMed
79.
Zurück zum Zitat 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 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.
Zurück zum Zitat 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):814–817PubMedPubMedCentral 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):814–817PubMedPubMedCentral
81.
Zurück zum Zitat 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):1947–1949PubMedPubMedCentral 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):1947–1949PubMedPubMedCentral
82.
Zurück zum Zitat 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):1828–1830PubMedPubMedCentral 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):1828–1830PubMedPubMedCentral
83.
Zurück zum Zitat Kempf VA, Trebesius K, Autenrieth IB (2000) Fluorescent in situ hybridization allows rapid identification of microorganisms in blood cultures. J Clin Microbiol 38(2):830–838PubMedPubMedCentral Kempf VA, Trebesius K, Autenrieth IB (2000) Fluorescent in situ hybridization allows rapid identification of microorganisms in blood cultures. J Clin Microbiol 38(2):830–838PubMedPubMedCentral
84.
Zurück zum Zitat 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):4186–4188PubMedPubMedCentral 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):4186–4188PubMedPubMedCentral
85.
Zurück zum Zitat Mullis KB, Faloona FA (1987) Specific synthesis of DNA in vitro via a polymerase-catalyzed chain reaction. Methods Enzymol 155:335–350PubMed Mullis KB, Faloona FA (1987) Specific synthesis of DNA in vitro via a polymerase-catalyzed chain reaction. Methods Enzymol 155:335–350PubMed
86.
Zurück zum Zitat 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):224–230PubMed 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):224–230PubMed
87.
Zurück zum Zitat 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):165–256PubMedPubMedCentral 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):165–256PubMedPubMedCentral
88.
Zurück zum Zitat 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):242–256PubMedPubMedCentral 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):242–256PubMedPubMedCentral
89.
Zurück zum Zitat Persing DH (1993) Diagnostic molecular microbiology. Current challenges and future directions. Diagn Microbiol Infect Dis 16(2):159–163PubMed Persing DH (1993) Diagnostic molecular microbiology. Current challenges and future directions. Diagn Microbiol Infect Dis 16(2):159–163PubMed
90.
Zurück zum Zitat 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):335–351PubMedPubMedCentral 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):335–351PubMedPubMedCentral
91.
Zurück zum Zitat 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):1161–1165PubMedPubMedCentral 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):1161–1165PubMedPubMedCentral
92.
Zurück zum Zitat 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):464–466PubMedPubMedCentral 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):464–466PubMedPubMedCentral
93.
Zurück zum Zitat 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):1169–1175PubMedPubMedCentral 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):1169–1175PubMedPubMedCentral
94.
Zurück zum Zitat 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):1654–1660PubMedPubMedCentral 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):1654–1660PubMedPubMedCentral
95.
Zurück zum Zitat 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):13–17PubMed 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):13–17PubMed
96.
Zurück zum Zitat 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):217–219PubMed 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):217–219PubMed
97.
Zurück zum Zitat 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):2541–2547PubMedPubMedCentral 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):2541–2547PubMedPubMedCentral
98.
Zurück zum Zitat 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 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
99.
Zurück zum Zitat 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):1001–1005PubMed 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):1001–1005PubMed
100.
Zurück zum Zitat 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):1721–1724PubMedPubMedCentral 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):1721–1724PubMedPubMedCentral
101.
Zurück zum Zitat 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):1553–1558PubMedPubMedCentral 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):1553–1558PubMedPubMedCentral
102.
Zurück zum Zitat 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):3641–3646PubMedPubMedCentral 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):3641–3646PubMedPubMedCentral
103.
Zurück zum Zitat 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):1626–1629PubMedPubMedCentral 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):1626–1629PubMedPubMedCentral
104.
Zurück zum Zitat 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):1106–1111PubMed 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):1106–1111PubMed
105.
Zurück zum Zitat 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):235–251PubMedPubMedCentral 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):235–251PubMedPubMedCentral
106.
Zurück zum Zitat 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 9:126PubMedPubMedCentral 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 9:126PubMedPubMedCentral
107.
Zurück zum Zitat 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):4432–4438PubMedPubMedCentral 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):4432–4438PubMedPubMedCentral
108.
Zurück zum Zitat Barken KB, Haagensen JA, Tolker-Nielsen T (2007) Advances in nucleic acid-based diagnostics of bacterial infections. Clin Chim Acta 384(1–2):1–11PubMed Barken KB, Haagensen JA, Tolker-Nielsen T (2007) Advances in nucleic acid-based diagnostics of bacterial infections. Clin Chim Acta 384(1–2):1–11PubMed
109.
Zurück zum Zitat 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):2810–2816PubMedPubMedCentral 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):2810–2816PubMedPubMedCentral
110.
Zurück zum Zitat Klouche M, Schroder U (2008) Rapid methods for diagnosis of bloodstream infections. Clin Chem Lab Med 46(7):888–908PubMed Klouche M, Schroder U (2008) Rapid methods for diagnosis of bloodstream infections. Clin Chem Lab Med 46(7):888–908PubMed
111.
Zurück zum Zitat 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):1439–1443PubMedPubMedCentral 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):1439–1443PubMedPubMedCentral
112.
Zurück zum Zitat 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):1811–1814PubMedPubMedCentral 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):1811–1814PubMedPubMedCentral
113.
Zurück zum Zitat 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):4211–4217PubMedPubMedCentral 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):4211–4217PubMedPubMedCentral
114.
Zurück zum Zitat 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 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.
Zurück zum Zitat Al-Soud WA, Radstrom P (2001) Purification and characterization of PCR-inhibitory components in blood cells. J Clin Microbiol 39(2):485–493PubMedPubMedCentral Al-Soud WA, Radstrom P (2001) Purification and characterization of PCR-inhibitory components in blood cells. J Clin Microbiol 39(2):485–493PubMedPubMedCentral
116.
Zurück zum Zitat 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):41–49PubMed 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):41–49PubMed
117.
Zurück zum Zitat 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):1747–1752PubMedPubMedCentral 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):1747–1752PubMedPubMedCentral
118.
Zurück zum Zitat 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):98–102PubMed 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):98–102PubMed
119.
Zurück zum Zitat Horz HP, Scheer S, Vianna ME, Conrads G (2010) New methods for selective isolation of bacterial DNA from human clinical specimens. Anaerobe 16(1):47–53PubMed Horz HP, Scheer S, Vianna ME, Conrads G (2010) New methods for selective isolation of bacterial DNA from human clinical specimens. Anaerobe 16(1):47–53PubMed
120.
Zurück zum Zitat 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):e72349PubMedPubMedCentral 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):e72349PubMedPubMedCentral
121.
Zurück zum Zitat 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):2629–2631PubMedPubMedCentral 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):2629–2631PubMedPubMedCentral
122.
Zurück zum Zitat 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):206–213PubMed 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):206–213PubMed
123.
Zurück zum Zitat 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 57:307–316PubMed 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 57:307–316PubMed
124.
Zurück zum Zitat 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):569–573PubMed 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):569–573PubMed
125.
Zurück zum Zitat 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):308–311PubMed 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):308–311PubMed
126.
Zurück zum Zitat 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):2919–2923PubMedPubMedCentral 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):2919–2923PubMedPubMedCentral
127.
Zurück zum Zitat 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):2759–2765PubMedPubMedCentral 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):2759–2765PubMedPubMedCentral
128.
Zurück zum Zitat 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):e38916PubMedPubMedCentral 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):e38916PubMedPubMedCentral
129.
Zurück zum Zitat 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 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
130.
Zurück zum Zitat 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 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
131.
Zurück zum Zitat 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):e87315PubMedPubMedCentral 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):e87315PubMedPubMedCentral
132.
Zurück zum Zitat Oliver JD (2005) The viable but nonculturable state in bacteria. J Microbiol 43:93–100PubMed Oliver JD (2005) The viable but nonculturable state in bacteria. J Microbiol 43:93–100PubMed
133.
Zurück zum Zitat 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):296–301PubMed 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):296–301PubMed
134.
Zurück zum Zitat 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):1913–1920PubMedPubMedCentral 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):1913–1920PubMedPubMedCentral
135.
Zurück zum Zitat 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):149–154PubMedPubMedCentral 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):149–154PubMedPubMedCentral
136.
Zurück zum Zitat Lindahl T (1993) Instability and decay of the primary structure of DNA. Nature 362(6422):709–715PubMed Lindahl T (1993) Instability and decay of the primary structure of DNA. Nature 362(6422):709–715PubMed
137.
Zurück zum Zitat 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):2273–2280PubMed 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):2273–2280PubMed
138.
Zurück zum Zitat 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):1707–1708PubMed 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):1707–1708PubMed
139.
Zurück zum Zitat 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):3308–3312PubMedPubMedCentral 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):3308–3312PubMedPubMedCentral
140.
Zurück zum Zitat 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):5111–5117PubMedPubMedCentral 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):5111–5117PubMedPubMedCentral
141.
Zurück zum Zitat Josephson KL, Gerba CP, Pepper IL (1993) Polymerase chain reaction detection of nonviable bacterial pathogens. Appl Environ Microbiol 59(10):3513–3515PubMedPubMedCentral Josephson KL, Gerba CP, Pepper IL (1993) Polymerase chain reaction detection of nonviable bacterial pathogens. Appl Environ Microbiol 59(10):3513–3515PubMedPubMedCentral
142.
Zurück zum Zitat 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):1313–1318PubMedPubMedCentral 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):1313–1318PubMedPubMedCentral
143.
Zurück zum Zitat 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):518–523PubMedPubMedCentral 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):518–523PubMedPubMedCentral
144.
Zurück zum Zitat 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):e3443PubMedPubMedCentral 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):e3443PubMedPubMedCentral
145.
Zurück zum Zitat 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):345–353PubMedPubMedCentral 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):345–353PubMedPubMedCentral
146.
Zurück zum Zitat 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):1057–1067PubMed 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):1057–1067PubMed
147.
Zurück zum Zitat 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):29–33PubMed 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):29–33PubMed
148.
Zurück zum Zitat 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):105–110PubMedPubMedCentral 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):105–110PubMedPubMedCentral
149.
Zurück zum Zitat 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):368–372PubMedPubMedCentral 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):368–372PubMedPubMedCentral
150.
Zurück zum Zitat van Vliet AH (2010) Next generation sequencing of microbial transcriptomes: challenges and opportunities. FEMS Microbiol Lett 302(1):1–7PubMed van Vliet AH (2010) Next generation sequencing of microbial transcriptomes: challenges and opportunities. FEMS Microbiol Lett 302(1):1–7PubMed
151.
Zurück zum Zitat 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):2267–2275PubMedPubMedCentral 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):2267–2275PubMedPubMedCentral
152.
Zurück zum Zitat 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):e65226PubMedPubMedCentral 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):e65226PubMedPubMedCentral
153.
Zurück zum Zitat 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):3268–3275PubMedPubMedCentral 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):3268–3275PubMedPubMedCentral
154.
Zurück zum Zitat 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 15:96PubMedPubMedCentral 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 15:96PubMedPubMedCentral
155.
Zurück zum Zitat Dalton WS, Friend SH (2006) Cancer biomarkers—an invitation to the table. Science 312(5777):1165–1168PubMed Dalton WS, Friend SH (2006) Cancer biomarkers—an invitation to the table. Science 312(5777):1165–1168PubMed
156.
Zurück zum Zitat 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):272–275PubMed 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):272–275PubMed
157.
Zurück zum Zitat Standage SW, Wong HR (2011) Biomarkers for pediatric sepsis and septic shock. Expert Rev Anti-Infect Ther 9(1):71–79PubMedPubMedCentral Standage SW, Wong HR (2011) Biomarkers for pediatric sepsis and septic shock. Expert Rev Anti-Infect Ther 9(1):71–79PubMedPubMedCentral
158.
Zurück zum Zitat 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):883–890PubMed 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):883–890PubMed
159.
Zurück zum Zitat 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):e53279PubMedPubMedCentral 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):e53279PubMedPubMedCentral
160.
Zurück zum Zitat 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):R192PubMedPubMedCentral 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):R192PubMedPubMedCentral
161.
Zurück zum Zitat 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):1418–1428PubMedPubMedCentral 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):1418–1428PubMedPubMedCentral
162.
163.
Zurück zum Zitat 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):R130PubMedPubMedCentral 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):R130PubMedPubMedCentral
164.
Zurück zum Zitat 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):225–229PubMed 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):225–229PubMed
165.
Zurück zum Zitat 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):R63PubMedPubMedCentral 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):R63PubMedPubMedCentral
166.
Zurück zum Zitat 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):45–50PubMedPubMedCentral 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):45–50PubMedPubMedCentral
167.
Zurück zum Zitat Silvestre J, Coelho L, Povoa P (2010) Should C-reactive protein concentration at ICU discharge be used as a prognostic marker? BMC Anesthesiol 10:17PubMedPubMedCentral Silvestre J, Coelho L, Povoa P (2010) Should C-reactive protein concentration at ICU discharge be used as a prognostic marker? BMC Anesthesiol 10:17PubMedPubMedCentral
168.
Zurück zum Zitat 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):176–180PubMed 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):176–180PubMed
169.
Zurück zum Zitat 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):206–217PubMed 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):206–217PubMed
170.
Zurück zum Zitat 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):210–217PubMed 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):210–217PubMed
171.
Zurück zum Zitat 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):1996–2003PubMed 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):1996–2003PubMed
172.
Zurück zum Zitat Reinhart K, Bauer M, Riedemann NC, Hartog CS (2012) New approaches to sepsis: molecular diagnostics and biomarkers. Clin Microbiol Rev 25(4):609–634PubMedPubMedCentral Reinhart K, Bauer M, Riedemann NC, Hartog CS (2012) New approaches to sepsis: molecular diagnostics and biomarkers. Clin Microbiol Rev 25(4):609–634PubMedPubMedCentral
173.
Zurück zum Zitat 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):5–14PubMed 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):5–14PubMed
174.
Zurück zum Zitat 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):467–474PubMedPubMedCentral 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):467–474PubMedPubMedCentral
175.
Zurück zum Zitat 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):1926–1933PubMed 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):1926–1933PubMed
176.
Zurück zum Zitat Eugen-Olsen J (2011) suPAR—a future risk marker in bacteremia. J Intern Med 270(1):29–31PubMed Eugen-Olsen J (2011) suPAR—a future risk marker in bacteremia. J Intern Med 270(1):29–31PubMed
177.
178.
Zurück zum Zitat 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):203–211PubMed 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):203–211PubMed
179.
Zurück zum Zitat Koch A, Tacke F (2012) Risk stratification and triage in the emergency department: has this become ‘suPAR’ easy? J Intern Med 272(3):243–246PubMed Koch A, Tacke F (2012) Risk stratification and triage in the emergency department: has this become ‘suPAR’ easy? J Intern Med 272(3):243–246PubMed
180.
Zurück zum Zitat Call DR, Bakko MK, Krug MJ, Roberts MC (2003) Identifying antimicrobial resistance genes with DNA microarrays. Antimicrob Agents Chemother 47(10):3290–3295PubMedPubMedCentral Call DR, Bakko MK, Krug MJ, Roberts MC (2003) Identifying antimicrobial resistance genes with DNA microarrays. Antimicrob Agents Chemother 47(10):3290–3295PubMedPubMedCentral
181.
Zurück zum Zitat 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):2291–2302PubMedPubMedCentral 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):2291–2302PubMedPubMedCentral
Metadaten
Titel
Developments for improved diagnosis of bacterial bloodstream infections
verfasst von
A. J. M. Loonen
P. F. G. Wolffs
C. A. Bruggeman
A. J. C. van den Brule
Publikationsdatum
01.10.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Clinical Microbiology & Infectious Diseases / Ausgabe 10/2014
Print ISSN: 0934-9723
Elektronische ISSN: 1435-4373
DOI
https://doi.org/10.1007/s10096-014-2153-4

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