By shortening the time to pathogen identification and allowing for detection of organisms missed by blood culture, new molecular methods may provide clinical benefits for the management of patients with sepsis. While a number of reviews on the diagnosis of sepsis have recently been published we here present up-to-date new developments including multiplex PCR, mass spectrometry and array techniques. We focus on those techniques that are commercially available and for which clinical studies have been performed and published.
1. R.S. Hotchkiss G. Monneret D. Payen 2013 Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nature Reviews Immunology 13 862 874.
2. D.C. Angus T. van der Poll 2013 Severe sepsis and septic shock The New England Journal of Medicine 369 840 851.
3. R.P. Dellinger M.M. Levy A. Rhodes D. Annane H. Gerlach 2013 Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012 Critical Care Medicine 41 580 637.
4. K. Reinhart M. Bauer N.C. Riedemann C.S. Hartog 2012 New approaches to sepsis: molecular diagnostics and biomarkers Clinical Microbiology Reviews 25 609 634.
5. P. Josefson K. Stralin A. Ohlin T. Ennefors B. Dragsten 2011 Evaluation of a commercial multiplex PCR test (Septi-Fast) in the etiological diagnosis of community-onset bloodstream infections European Journal of Clinical Microbiology & Infectious Diseases: official publication of the European Society of Clinical Microbiology 30 1127 1134.
6. A. Kumar C. Haery B. Paladugu S. Symeoneides L. Taiberg 2006 The duration of hypotension before the initiation of antibiotic treatment is a critical determinant of survival in a murine model of Escherichia coli septic shock: association with serum lactate and inflammatory cytokine levels The Journal of Infectious Diseases 193 251 258.
7. P. Nordmann M. Gniadkowski C.G. Giske L. Poirel N. Woodford 2012 Identification and screening of carbapenemase-producing Enterobacteriaceae Clinical Microbiology and Infection: the official publication of the European Society of Clinical Microbiology and Infectious Diseases 18 432 438.
8. A.J. Labelle S.T. Micek N. Roubinian M.H. Kollef 2008 Treatment-related risk factors for hospital mortality in Candida bloodstream infections Critical Care Medicine 36 2967 2972.
9. K.W. Garey M. Rege M.P. Pai D.E. Mingo K.J. Suda 2006 Time to initiation of fluconazole therapy impacts mortality in patients with candidemia: a multi-institutional study Clinical Infectious Diseases: an official publication of the Infectious Diseases Society of America 43 25 31.
10. R.P. Dellinger M.M. Levy J.M. Carlet J. Bion M.M. Parker 2008 Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008 Intensive Care Medicine 34 17 60.
11. B. Coburn A.M. Morris G. Tomlinson A.S. Detsky 2012 Does this adult patient with suspected bacteremia require blood cultures JAMA: the journal of the American Medical Association 308 502 511.
12. J. Barenfanger D.R. Graham L. Kolluri G. Sangwan J. Lawhorn 2008 Decreased mortality associated with prompt Gram staining of blood cultures American Journal of Clinical Pathology 130 870 876.
13. R. Patel E.A. Vetter W.S. Harmsen C.D. Schleck H.J. Fadel 2011 Optimized pathogen detection with 30- compared to 20-milliliter blood culture draws Journal of Clinical Microbiology 49 4047 4051.
14. T.J. Kirn M.P. Weinstein 2013 Update on blood cultures: how to obtain, process, report, and interpret Clinical Microbiology and Infection: the official publication of the European Society of Clinical Microbiology and Infectious Diseases 19 513 520.
15. N. Mancini S. Carletti N. Ghidoli P. Cichero R. Burioni 2010 The era of molecular and other non-culture-based methods in diagnosis of sepsis Clinical Microbiology Reviews 23 235 251.
16. S. Varani M. Stanzani M. Paolucci F. Melchionda G. Castellani 2009 Diagnosis of bloodstream infections in immunocompromised patients by real-time PCR The Journal of Infection 58 346 351.
17. J. Alvarez J. Mar E. Varela-Ledo M. Garea L. Matinez-Lamas 2012 Cost analysis of real-time polymerase chain reac tion microbiological diagnosis in patients with septic shock Anaesthesia and Intensive Care 40 958 963.
18. A.M. Caliendo D.N. Gilbert C.C. Ginocchio K.E. Hanson L. May 2013 Better tests, better care: improved diagnostics for infectious diseases Clinical Infectious Diseases: an official publication of the Infectious Diseases Society of America 57 3 S139 S170.
19. D.J. Ecker R. Sampath H. Li C. Massire H.E. Matthews 2010 New technology for rapid molecular diagnosis of bloodstream infections Expert Review of Molecular Diagnostics 10 399 415.
20. N. Leggieri A. Rida P. Francois J. Schrenzel 2010 Molecular diagnosis of bloodstream infections: planning to (physically) reach the bedside Current Opinion in Infectious Diseases 23 311 319.
21. M. Venkatesh A. Flores R.A. Luna J. Versalovic 2010 Molecular microbiological methods in the diagnosis of neonatal sepsis Expert Review of Anti-infective Therapy 8 1037 1048.
22. M.S. Rangel-Frausto D. Pittet M. Costigan T. Hwang C.S. Davis 1995 The natural history of the systemic inflammatory response syndrome (SIRS) A prospective study. JAMA: the journal of the American Medical Association 273 117 123.
23. D.C. Angus W.T. Linde-Zwirble J. Lidicker G. Clermont J. Carcillo 2001 Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care Critical Care Medicine 29 1303 1310.
24. T. Lagu M.B. Rothberg M.S. Shieh P.S. Pekow J.S. Steingrub 2012 Hospitalizations, costs, and outcomes of severe sepsis in the United States 2003 to 2007 Critical Care Medicine 40 754 761.
25. V.M. Ranieri B.T. Thompson P.S. Barie J.F. Dhainaut I.S. Douglas 2012 Drotrecogin alfa (activated) in adults with septic shock The New England Journal of Medicine 366 2055 2064.
26. J.L. Vincent J. Rello J. Marshall E. Silva A. Anzueto 2009 International study of the prevalence and outcomes of infection in intensive care units JAMA: the journal of the American Medical Association 302 2323 2329.
27. S.M. Opal G.E. Garber S.P. LaRosa D.G. Maki R.C. Freebairn 2003 Systemic host responses in severe sepsis analyzed by causative microorganism and treatment effects of drotrecogin alfa (activated) Clinical Infectious Diseases: an official publication of the Infectious Diseases Society of America 37 50 58.
28. G.S. Martin D.M. Mannino S. Eaton M. Moss 2003 The epidemiology of sepsis in the United States from 1979 through 2000 The New England Journal of Medicine 348 1546 1554.
29. F.B. Mayr S. Yende W.T. Linde-Zwirble O.M. Peck-Palmer A.E. Barnato 2010 Infection rate and acute organ dysfunction risk as explanations for racial differences in severe sepsis JAMA: the journal of the American Medical Association 303 2495 2503.
30. N.P. O'Grady P.S. Barie J.G. Bartlett T. Bleck K. Carroll 2008 Guidelines for evaluation of new fever in critically ill adult patients: 2008 update from the American College of Critical Care Medicine and the Infectious Diseases Society of America Critical Care Medicine 36 1330 1349.
31. R. Zadroga D.N. Williams R. Gottschall K. Hanson V. Nordberg 2013 Comparison of 2 blood culture media shows significant differences in bacterial recovery for patients on antimicrobial therapy Clinical Infectious Diseases: an official publication of the Infectious Diseases Society of America 56 790 797.
32. J. Valles J. Rello A. Ochagavia J. Garnacho M.A. Alcala 2003 Community-acquired bloodstream infection in critically ill adult patients: impact of shock and inappropriate antibiotic therapy on survival Chest 123 1615 1624.
33. R.L. Sautter A.R. Bills D.L. Lang G. Ruschell B.J. Heiter 2006 Effects of delayed-entry conditions on the recovery and detection of microorganisms from BacT/ALERT and BACTEC blood culture bottles Journal of Clinical Microbiology 44 1245 1249.
34. I. Schwetz G. Hinrichs E.C. Reisinger G.J. Krejs H. Olschewski 2007 Delayed processing of blood samples influences time to positivity of blood cultures and results of Gram stain-acridine orange leukocyte Cytospin test Journal of Clinical Microbiology 45 2691 2694.
35. E.L. Tsalik D. Jones B. Nicholson L. Waring O. Liesenfeld 2010 Multiplex PCR to diagnose bloodstream infections in patients admitted from the emergency department with sepsis Journal of Clinical Microbiology 48 26 33.
36. P. Moreillon Y.A. Que 2004 Infective endocarditis Lancet 363 139 149.
37. R.W. Watkin S. Lang P.A. Lambert W.A. Littler T.S. Elliott 2003 The microbial diagnosis of infective endocarditis The Journal of Infection 47 1 11.
38. C.J. Clancy M.H. Nguyen 2013 Finding the “missing 50%” of invasive candidiasis: how nonculture diagnostics will improve understanding of disease spectrum and transform patient care Clinical Infectious Diseases: an official publication of the Infectious Diseases Society of America 56 1284 1292.
39. R.P. Dellinger M.M. Levy J.M. Carlet J. Bion M.M. Parker 2008 Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008 Critical Care Medicine 36 296 327.
40. K.C. Chapin M.C. Musgnug 2003 Direct susceptibility testing of positive blood cultures by using Sensititre broth microdilution plates Journal of Clinical Microbiology 41 4751 4754.
41. L.G. Bekeris J.A. Tworek M.K. Walsh P.N. Valenstein 2005 Trends in blood culture contamination: a College of American Pathologists Q-Tracks study of 356 institutions Archives of Pathology & Laboratory Medicine 129 1222 1225.
42. R.M. Gander L. Byrd M. DeCrescenzo S. Hirany M. Bowen 2009 Impact of blood cultures drawn by phlebotomy on contamination rates and health care costs in a hospital emergency department Journal of Clinical Microbiology 47 1021 1024.
43. S. Halverson P.N. Malani D.W. Newton A. Habicht K. Vander Have 2013 Impact of hourly emergency department patient volume on blood culture contamination and diagnostic yield Journal of Clinical Microbiology 51 1721 1726.
44. N.H. Kim M. Kim S. Lee N.R. Yun K.H. Kim 2011 Effect of routine sterile gloving on contamination rates in blood culture: a cluster randomized trial Annals of Internal Medicine 154 145 151.
45. J.M. Boyce J. Nadeau D. Dumigan D. Miller C. Dubowsky 2013 Obtaining blood cultures by venipuncture versus from central lines: impact on blood culture contamination rates and potential effect on central line-associated blood-stream infection reporting Infection Control and Hospital Epidemiology: the official journal of the Society of Hospital Epidemiologists of America 34 1042 1047.
46. H. Russmann V.A. Kempf S. Koletzko J. Heesemann I.B. Autenrieth 2001 Comparison of fluorescent in situ hybridization and conventional culturing for detection of Helicobacter pylori in gastric biopsy specimens Journal of Clinical Microbiology 39 304 308.
47. V.A. Kempf T. Mandle U. Schumacher A. Schafer I.B. Autenrieth 2005 Rapid detection and identification of pathogens in blood cultures by fluorescence in situ hybridization and flow cytometry International Journal of Medical Microbiology: IJMM 295 47 55.
48. K. Oliveira G. Haase C. Kurtzman J.J. Hyldig-Nielsen H. Stender 2001 Differentiation of Candida albicans and Candida dubliniensis by fluorescent in situ hybridization with peptide nucleic acid probes Journal of Clinical Microbiology 39 4138 4141.
49. M. Paolucci M.P. Landini V. Sambri 2010 Conventional and molecular techniques for the early diagnosis of bacteraemia International Journal of Antimicrobial Agents 36 2 S6 S16.
50. K. Chapin M. Musgnug 2003 Evaluation of three rapid methods for the direct identification of Staphylococcus aureus from positive blood cultures Journal of Clinical Microbiology 41 4324 4327.
51. K. Oliveira S.M. Brecher A. Durbin D.S. Shapiro D.R. Schwartz 2003 Direct identification of Staphylococcus aureus from positive blood culture bottles Journal of Clinical Microbiology 41 889 891.
52. J.R. Shepard R.M. Addison B.D. Alexander P. Della-Latta M. Gherna 2008 Multicenter evaluation of the Candida albicans/Candida glabrata peptide nucleic acid fluorescent in situ hybridization method for simultaneous dual-color identification of C. albicans and C. glabrata directly from blood culture bottles Journal of Clinical Microbiology 46 50 55.
53. T.E. Davis D.D. Fuller 1991 Direct identification of bacterial isolates in blood cultures by using a DNA probe Journal of Clinical Microbiology 29 2193 2196.
54. L. Lindholm H. Sarkkinen 2004 Direct identification of grampositive cocci from routine blood cultures by using Accu-Probe tests Journal of Clinical Microbiology 42 5609 5613.
55. Q. Qian Y.W. Tang C.P. Kolbert C.A. Torgerson J.G. Hughes 2001 Direct identification of bacteria from positive blood cultures by amplification and sequencing of the 16S rRNA gene: evaluation of BACTEC 9240 instrument true-positive and false-positive results Journal of Clinical Microbiology 39 3578 3582.
56. C.Y. Turenne E. Witwicki D.J. Hoban J.A. Karlowsky A.M. Kabani 2000 Rapid identification of bacteria from positive blood cultures by fluorescence-based PCR-single-strand conformation polymorphism analysis of the 16S rRNA gene Journal of Clinical Microbiology 38 513 520.
57. S. Gebert D. Siegel N. Wellinghausen 2008 Rapid detection of pathogens in blood culture bottles by real-time PCR in conjunction with the pre-analytic tool MolYsis The Journal of Infection 57 307 316.
58. N. Wellinghausen B. Wirths A. Essig L. Wassill 2004 Evaluation of the Hyplex BloodScreen Multiplex PCR-Enzyme-linked immunosorbent assay system for direct identification of gram-positive cocci and gram-negative bacilli from positive blood cultures Journal of Clinical Microbiology 42 3147 3152.
59. E.J. Kaleta A.E. Clark D.R. Johnson D.C. Gamage V.H. Wysocki 2011 Use of PCR coupled with electrospray ionization mass spectrometry for rapid identification of bacterial and yeast bloodstream pathogens from blood culture bottles Journal of Clinical Microbiology 49 345 353.
60. D. Jacob U. Sauer R. Housley C. Washington K. Sannes-Lowery 2012 Rapid and high-throughput detection of highly pathogenic bacteria by Ibis PLEX-ID technology PloS One 7 39928.
61. Y.W. Tang A. Kilic Q. Yang S.K. McAllister H. Li 2007 StaphPlex system for rapid and simultaneous identification of antibiotic resistance determinants and Panton-Valentine leukocidin detection of staphylococci from positive blood cultures Journal of Clinical Microbiology 45 1867 1873.
62. P.D. Stamper M. Cai T. Howard S. Speser K.C. Carroll 2007 Clinical validation of the molecular BD GeneOhm StaphSR assay for direct detection of Staphylococcus aureus and methicillin-resistant Staphylococcus aureus in positive blood cultures Journal of Clinical Microbiology 45 2191 2196.
63. J.W. Snyder G.K. Munier S.A. Heckman P. Camp T.L. Overman 2009 Failure of the BD GeneOhm StaphSR assay for direct detection of methicillin-resistant and methicillin-susceptible Staphylococcus aureus isolates in positive blood cultures collected in the United States Journal of Clinical Microbiology 47 3747 3748.
64. D.M. Wolk M.J. Struelens P. Pancholi T. Davis P. Della-Latta 2009 Rapid detection of Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) in wound specimens and blood cultures: multicenter preclinical evaluation of the Cepheid Xpert MRSA/SA skin and soft tissue and blood culture assays Journal of Clinical Microbiology 47 823 826.
65. A. Innings M. Krabbe M. Ullberg B. Herrmann 2005 Identification of 43 Streptococcus species by pyrosequencing analysis of the rnpB gene Journal of Clinical Microbiology 43 5983 5991.
66. M. Haanpera J. Jalava P. Huovinen O. Meurman K. Rantakokko-Jalava 2007 Identification of alpha-hemolytic streptococci by pyrosequencing the 16S rRNA gene and by use of VITEK 2 Journal of Clinical Microbiology 45 762 770.
67. M. Tarnberg T. Jakobsson J. Jonasson U. Forsum 2002 Identification of randomly selected colonies of lactobacilli from normal vaginal fluid by pyrosequencing of the 16S rDNA variable V1 and V3 regions APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica 110 802 810.
68. J.A. Jordan A.R. Butchko M.B. Durso 2005 Use of pyrosequencing of 16S rRNA fragments to differentiate between bacteria responsible for neonatal sepsis The journal of molecular diagnostics: JMD 7 105 110.
69. I. Quiles-Melero J. Garcia-Rodriguez M.P. Romero-Gomez P. Gomez-Sanchez J. Mingorance 2011 Rapid identification of yeasts from positive blood culture bottles by pyrosequencing European Journal of Clinical Microbiology & Infectious Diseases: official publication of the European Society of Clinical Microbiology 30 21 24.
70. M. Motoshima K. Yanagihara Y. Morinaga J. Matsuda H. Hasegawa 2012 Identification of bacteria directly from positive blood culture samples by DNA pyrosequencing of the 16S rRNA gene Journal of Medical Microbiology 61 1556 1562.
71. R.P. Peters T. Mohammadi C.M. Vandenbroucke-Grauls S.A. Danner M.A. van Agtmael 2004 Detection of bacterial DNA in blood samples from febrile patients: underestimated infection or emerging contamination FEMS Immunology and Medical Microbiology 42 249 253.
72. P. Seng M. Drancourt F. Gouriet B. La Scola P.E. Fournier 2009 Ongoing revolution in bacteriology: routine identification of bacteria by matrix-assisted laser desorption ionization time-of-flight mass spectrometry Clinical Infectious Diseases: an official publication of the Infectious Diseases Society of America 49 543 551.
73. S. Schubert K. Weinert C. Wagner B. Gunzl A. Wieser 2011 Novel, improved sample preparation for rapid, direct identification from positive blood cultures using matrixassisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry The journal of molecular diagnostics: JMD 13 701 706.
74. B. La Scola D. Raoult 2009 Direct identification of bacteria in positive blood culture bottles by matrix-assisted laser desorption ionisation time-of-flight mass spectrometry PloS One 4 8041.
75. B. La Scola 2011 Intact cell MALDI-TOF mass spectrometrybased approaches for the diagnosis of bloodstream infections Expert Review of Molecular Diagnostics 11 287 298.
76. A. Cherkaoui J. Hibbs S. Emonet M. Tangomo M. Girard 2010 Comparison of two matrix-assisted laser desorption ionization-time of flight mass spectrometry methods with conventional phenotypic identification for routine identification of bacteria to the species level Journal of Clinical Microbiology 48 1169 1175.
77. U. Eigner M. Holfelder K. Oberdorfer U. Betz-Wild D. Bertsch 2009 Performance of a matrix-assisted laser desorption ionization-time-of-flight mass spectrometry system for the identification of bacterial isolates in the clinical routine laboratory Clinical Laboratory 55 289 296.
78. G. Marklein M. Josten U. Klanke E. Muller R. Horre 2009 Matrix-assisted laser desorption ionization-time of flight mass spectrometry for fast and reliable identification of clinical yeast isolates Journal of Clinical Microbiology 47 2912 2917.
79. O. Bader M. Weig L. Taverne-Ghadwal R. Lugert U. Gross 2011 Improved clinical laboratory identification of human pathogenic yeasts by matrix-assisted laser desorption ionization time-of-flight mass spectrometry Clinical Microbiology and Infection: the official publication of the European Society of Clinical Microbiology and Infectious Diseases 17 1359 1365.
80. O. Clerc G. Prod'hom C. Vogne A. Bizzini T. Calandra 2013 Impact of matrix-assisted laser desorption ionization time-of-flight mass spectrometry on the clinical management of patients with Gram-negative bacteremia: a prospective observational study Clinical Infectious Diseases: an official publication of the Infectious Diseases Society of America 56 1101 1107.
81. A.M. Huang D. Newton A. Kunapuli T.N. Gandhi L.L. Washer 2013 Impact of rapid organism identification via matrix-assisted laser desorption/ionization time-of-flight combined with antimicrobial stewardship team intervention in adult patients with bacteremia and candidemia Clinical Infectious Diseases: an official publication of the Infectious Diseases Society of America 57 1237 1245.
82. P. Tissari A. Zumla E. Tarkka S. Mero L. Savolainen 2010 Accurate and rapid identification of bacterial species from positive blood cultures with a DNA-based microarray platform: an observational study Lancet 375 224 230.
83. A. Aittakorpi P. Kuusela P. Koukila-Kahkola M. Vaara M. Petrou 2012 Accurate and rapid identification of Candida spp. frequently associated with fungemia by using PCR and the microarray-based Prove-it Sepsis assay Journal of Clinical Microbiology 50 3635 3640.
84. S. Laakso M. Maki 2013 Assessment of a semi-automated protocol for multiplex analysis of sepsis-causing bacteria with spiked whole blood samples MicrobiologyOpen 2 284 292.
85. O. Altun M. Almuhayawi M. Ullberg V. Ozenci 2013 Clinical evaluation of filmarray(R) blood culture ID panel in identification of bacteria and yeast from positive blood culture bottles Journal of Clinical Microbiology 51 4130 4136.
86. L.J. Scott 2013 Verigene(R) gram-positive blood culture nucleic acid test Molecular Diagnosis & Therapy 17 117 122.
87. L.P. Samuel R.J. Tibbetts A. Agotesku M. Fey R. Hensley 2013 Evaluation of a microarray-based assay for rapid identification of Gram-positive organisms and resistance markers in positive blood cultures Journal of Clinical Microbiology 51 1188 1192.
88. K.V. Sullivan N.N. Turner S.S. Roundtree S. Young C.A. Brock-Haag 2013 Rapid detection of gram-positive organisms by use of the verigene gram-positive blood culture nucleic acid test and the bacT/Alert pediatric FAN system in a multicenter pediatric evaluation Journal of Clinical Microbiology 51 3579 3584.
89. R.P. Peters M.A. van Agtmael S.A. Danner P.H. Savelkoul C.M. Vandenbroucke-Grauls 2004 New developments in the diagnosis of bloodstream infections The Lancet Infectious Diseases 4 751 760.
90. M. Paolucci M.G. Capretti P. Dal Monte L. Corvaglia M.P. Landini 2009 Laboratory diagnosis of late-onset sepsis in newborns by multiplex real-time PCR Journal of Medical Microbiology 58 533 534.
91. N. Wellinghausen A.J. Kochem C. Disque H. Muhl S. Gebert 2009 Diagnosis of bacteremia in whole-blood samples by use of a commercial universal 16S rRNA gene-based PCR and sequence analysis Journal of Clinical Microbiology 47 2759 2765.
92. K. Grif I. Heller W.M. Prodinger K. Lechleitner C. Lass-Florl 2012 Improvement of detection of bacterial pathogens in normally sterile body sites with a focus on orthopedic samples by use of a commercial 16S rRNA broad-range PCR and sequence analysis Journal of Clinical Microbiology 50 2250 2254.
93. C. Fitting M. Parlato M. Adib-Conquy N. Memain F. Philippart 2012 DNAemia detection by multiplex PCR and biomarkers for infection in systemic inflammatory response syndrome patients PloS One 7 38916.
94. F. Bloos S. Sachse A. Kortgen M.W. Pletz M. Lehmann 2012 Evaluation of a polymerase chain reaction assay for pathogen detection in septic patients under routine condition: an observational study PloS One 7 46003.
95. L.E. Lehmann K.P. Hunfeld T. Emrich G. Haberhausen H. Wissing 2008 A multiplex real-time PCR assay for rapid detection and differentiation of 25 bacterial and fungal pathogens from whole blood samples Medical Microbiology and Immunology 197 313 324.
96. B.J. Regueiro E. Varela-Ledo L. Martinez-Lamas J. Rodriguez-Calvino A. Aguilera 2010 Automated extraction improves multiplex molecular detection of infection in septic patients PloS One 5 13387.
97. H. Westh G. Lisby F. Breysse B. Boddinghaus M. Chomarat 2009 Multiplex real-time PCR and blood culture for identification of bloodstream pathogens in patients with suspected sepsis Clinical Microbiology and Infection: the official publication of the European Society of Clinical Microbiology and Infectious Diseases 15 544 551.
98. L.E. Lehmann J. Alvarez K.P. Hunfeld A. Goglio G.J. Kost 2009 Potential clinical utility of polymerase chain reaction in microbiological testing for sepsis Critical Care Medicine 37 3085 3090.
99. S.S. Chang W.H. Hsieh T.S. Liu S.H. Lee C.H. Wang 2013 Multiplex PCR system for rapid detection of pathogens in patients with presumed sepsis — a systemic review and meta-analysis PloS One 8 62323.
100. R.F. Louie Z. Tang T.E. Albertson S. Cohen N.K. Tran 2008 Multiplex polymerase chain reaction detection enhancement of bacteremia and fungemia Critical Care Medicine 36 1487 1492.
101. F. Wallet C. Loiez S. Herwegh R.J. Courcol 2011 Usefulness of real-time PCR for the diagnosis of sepsis in ICU-acquired infections Infectious Disorders Drug Targets 11 348 353.
102. C. Dierkes B. Ehrenstein S. Siebig H.J. Linde U. Reischl 2009 Clinical impact of a commercially available multiplex PCR system for rapid detection of pathogens in patients with presumed sepsis BMC Infectious Diseases 9 126.
103. F. Bloos F. Hinder K. Becker S. Sachse D. A. Mekontso 2010 A multicenter trial to compare blood culture with polymerase chain reaction in severe human sepsis Intensive Care Medicine 36 241 247.
104. S. Hettwer J. Wilhelm M. Schurmann H. Ebelt D. Hammer 2012 Microbial diagnostics in patients with presumed severe infection in the emergency department Medizinische Klinik, Intensivmedizin und Notfallmedizin 107 53 62.
105. M. von Lilienfeld-Toal L.E. Lehmann A.D. Raadts C. Hahn-Ast K.S. Orlopp 2009 Utility of a commercially available multiplex real-time PCR assay to detect bacterial and fungal pathogens in febrile neutropenia Journal of Clinical Microbiology 47 2405 2410.
106. N. Mancini D. Clerici R. Diotti M. Perotti N. Ghidoli 2008 Molecular diagnosis of sepsis in neutropenic patients with haematological malignancies Journal of Medical Microbiology 57 601 604.
107. F. Lamoth K. Jaton G. Prod'hom L. Senn J. Bille 2010 Multiplex blood PCR in combination with blood cultures for improvement of microbiological documentation of infection in febrile neutropenia Journal of Clinical Microbiology 48 3510 3516.
108. M. Guido M. Quattrocchi A. Zizza G. Pasanisi V. Pavone 2012 Molecular approaches in the diagnosis of sepsis in neutropenic patients with haematological malignances Journal of Preventive Medicine and Hygiene 53 104 108.
109. E. Idelevich Y. Niederbracht H. Penner S. Tafelski I. Nachtigall W.E. Berdel G. Peters G. Silling K. Becker 2013 Utility of the LightCycler® SeptiFast test in haematologic patients with neutropenic fever or sepsis: a randomized controlled trial European Conference of Clinical Microbiology and Infectious Diseases (ECCMID). Berlin, Germany.
110. N. Mancini S. Carletti N. Ghidoli P. Cichero C.M. Ossi 2009 Molecular diagnosis of polymicrobial sepsis Journal of Clinical Microbiology 47 1274 1275.
111. J. Steinmann J. Buer P.M. Rath A. Paul F. Saner 2009 Invasive aspergillosis in two liver transplant recipients: diagnosis by SeptiFast Transplant Infectious Disease: an official journal of the Transplantation Society 11 175 178.
112. F. Wallet S. Nseir L. Baumann S. Herwegh B. Sendid 2010 Preliminary clinical study using a multiplex real-time PCR test for the detection of bacterial and fungal DNA directly in blood Clinical Microbiology and Infection: the official publication of the European Society of Clinical Microbiology and Infectious Diseases 16 774 779.
113. E. Tschiedel J. Steinmann J. Buer J.G. Onnebrink U. Felderhoff-Muser 2012 Results and relevance of molecular detection of pathogens by SeptiFast — a retrospective analysis in 75 critically ill children Klinische Padiatrie 224 12 16.
114. S. Tafelski I. Nachtigall E.A. Idelevich G. Silling K. Becker J. Faust T. Trefzer A. Tamarkin T. Adam S. Bereswill M. Deja C. Spies 2013 Impact of Septi-Fast for pathogen detection in critical-care patients with sepsis: results from a randomized controlled clinical trial European Conference of Clinical Microbiology and Infectious Diseases (ECCMID). Berlin, Germany.
115. E. Cambau R. Courcol V. Veerabudun S. Bretagne I. Durand-Zaleski S. Bastuji-Garin on behalf of the EVAMICA group 2013 Does performing DNA detection in blood improve the microbial diagnosis of severe infections? First results of the EVAMICA study European Conference of Clinical Microbiology and Infectious Diseases (ECCMID). Berlin, Germany.
116. N.K. Tran D.G. Greenhalgh T.L. Palmieri G.J. Kost 2011 Multiplex PCR pathogen detection in two severely burned patients with suspected septicemia Journal of Burn Care & Research: official publication of the American Burn Association 32 172 177.
117. P.M. Rath F. Saner A. Paul N. Lehmann E. Steinmann 2012 Multiplex PCR for rapid and improved diagnosis of bloodstream infections in liver transplant recipients Journal of Clinical Microbiology 50 2069 2071.
118. A. Chaidaroglou E. Manoli E. Marathias A. Gkouziouta G. Saroglou 2013 Use of a multiplex polymerase chain reaction system for enhanced bloodstream pathogen detection in thoracic transplantation The journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 32 707 713.
119. B. Lucignano S. Ranno O. Liesenfeld B. Pizzorno L. Putignani 2011 Multiplex PCR allows rapid and accurate diagnosis of bloodstream infections in newborns and children with suspected sepsis Journal of Clinical Microbiology 49 2252 2258.
120. E. Torres-Martos M. Perez-Ruiz I. Pedrosa-Corral M. Pena-Caballero M. [ Jimenez-Valera 2013 Evaluation of the LightCycler® SeptiFast test in newborns and infants with clinical suspicion of sepsis Enfermedades Infecciosas y Microbiologia Clinica 31 375 379.
121. D.C. Kasper I. Altiok T.P. Mechtler J. Bohm J. Straub 2013 Molecular detection of late-onset neonatal sepsis in premature infants using small blood volumes: proof-of-concept Neonatology 103 268 273.
122. J.P. Casalta F. Gouriet V. Roux F. Thuny G. Habib 2009 Evaluation of the LightCycler® SeptiFast test in the rapid etiologic diagnostic of infectious endocarditis European journal of Clinical Microbiology & Infectious Diseases: official publication of the European Society of Clinical Microbiology 28 569 573.
123. A. Lefort L. Chartier B. Sendid M. Wolff J.L. Mainardi 2012 Diagnosis, management and outcome of Candida endocarditis Clinical Microbiology and Infection: the official publication of the European Society of Clinical Microbiology and Infectious Diseases 18 E99 E109.
124. L.E. Lehmann S. Hauser T. Malinka S. Klaschik S.U. Weber 2011 Rapid qualitative urinary tract infection pathogen identification by SeptiFast real-time PCR PloS One 6 17146.
125. B. Appenrodt L.E. Lehmann L. Thyssen M. Gentemann C. Rabe 2010 Is detection of bacterial DNA in ascitic fluid of clinical relevance European Journal of Gastroenterology & Hepatology 22 1487 1494.
126. A.L. Fernandez E. Varela L. Martinez A. Martinez J. Sierra 2010 Evaluation of a multiplex real-time PCR assay for detecting pathogens in cardiac valve tissue in patients with endocarditis Revista Espanola de Cardiologia 63 1205 1208.
127. E. Leitner H.H. Kessler W. Spindelboeck M. Hoenigl C. Putz-Bankuti 2013 Comparison of two molecular assays with conventional blood culture for diagnosis of sepsis Journal of Microbiological Methods 92 253 255.
128. J. Schreiber A. Nierhaus S.A. Braune G. de Heer S. Kluge 2013 Comparison of three different commercial PCR assays for the detection of pathogens in critically ill sepsis patients Medizinische Klinik, Intensivmedizin und Notfallmedizin 108 311 318.
129. T. Hansen B. Skanseng J. Hoorfar C. Lofstrom 2013 Evaluation of direct 16S rDNA sequencing as a metagenomics-based approach to screening bacteria in bottled water Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science 11 1 S158 S165.
130. M. Handschur H. Karlic C. Hertel M. Pfeilstocker A.G. Haslberger 2009 Preanalytic removal of human DNA eliminates false signals in general 16S rDNA PCR monitoring of bacterial pathogens in blood Comparative Immunology, Microbiology and Infectious Diseases 32 207 219.
131. H. Wiesinger-Mayr E. Jordana-Lluch E. Martro S. Schoenthaler C. Noehammer 2011 Establishment of a semi-automated pathogen DNA isolation from whole blood and comparison with commercially available kits Journal of Microbiological Methods 85 206 213.
132. M.J. Torres A. Criado M. Ruiz A.C. Llanos J.C. Palomares 2003 Improved real-time PCR for rapid detection of rifampin and isoniazid resistance in Mycobacterium tuberculosis clinical isolates Diagnostic Microbiology and Infectious Disease 45 207 212.
133. D.M. Leinberger V. Grimm M. Rubtsova J. Weile K. Schroppel 2010 Integrated detection of extended-spectrumbeta-lactam resistance by DNA microarray-based genotyping of TEM, SHV, and CTX-M genes Journal of Clinical Microbiology 48 460 471.
134. D. Raoult P.E. Fournier M. Drancourt 2004 What does the future hold for clinical microbiology Nature Reviews Microbiology 2 151 159.
135. S. Karumaa P. Karpanoja H. Sarkkinen 2012 PCR identification of bacteria in blood culture does not fit the daily workflow of a routine microbiology laboratory Journal of Clinical Microbiology 50 1031 1033.
136. P.R. Murray H. Masur 2012 Current approaches to the diagnosis of bacterial and fungal bloodstream infections in the intensive care unit Critical Care Medicine 40 3277 3282.
137. K.K. Perez R.J. Olsen W.L. Musick P.L. Cernoch J.R. Davis 2013 Integrating rapid pathogen identification and antimicrobial stewardship significantly decreases hospital costs Archives of Pathology & Laboratory Medicine 137 1247 1254.
138. H. Hebart L. Klingspor T. Klingebiel J. Loeffler J. Tollemar 2009 A prospective randomized controlled trial comparing PCR-based and empirical treatment with liposomal amphotericin B in patients after allo-SCT Bone Marrow Transplantation 43 553 561.
139. L.R. Stoneking A.E. Patanwala J.P. Winkler A.B. Fiorello E.S. Lee 2013 Would earlier microbe identification alter antibiotic therapy in bacteremic emergency department patients The journal of Emergency Medicine 44 1 8.
140. M.W. Pletz N. Wellinghausen T. Welte 2011 Will polymerase chain reaction (PCR)-based diagnostics improve outcome in septic patients A clinical view. Intensive Care Medicine 37 1069 1076.
141. S. Heenen F. Jacobs J.L. Vincent 2012 Antibiotic strategies in severe nosocomial sepsis: why do we not de-escalate more often Critical Care Medicine 40 1404 1409.
142. M. Mussap M.P. Molinari E. Senno P. Gritti B. Soro 2007 New diagnostic tools for neonatal sepsis: the role of a realtime polymerase chain reaction for the early detection and identification of bacterial and fungal species in blood samples Journal of Chemotherapy 19 2 31 34.
143. A. Vince S.Z. Lepej B. Barsic D. Dusek Z. Mitrovic 2008 LightCycler SeptiFast assay as a tool for the rapid diagnosis of sepsis in patients during antimicrobial therapy Journal of Medical Microbiology 57 1306 1307.
144. U. Lodes B. Bohmeier H. Lippert B. Konig F. Meyer 2012 PCRbased rapid sepsis diagnosis effectively guides clinical treatment in patients with new onset of SIRS Langenbeck's Archives of Surgery / Deutsche Gesellschaft für Chirurgie 397 447 455.
145. L.E. Lehmann K.P. Hunfeld M. Steinbrucker V. Brade M. Book 2010 Improved detection of blood stream pathogens by real-time PCR in severe sepsis Intensive Care Medicine 36 49 56.
146. K. Yanagihara Y. Kitagawa M. Tomonaga K. Tsukasaki S. Kohno 2010 Evaluation of pathogen detection from clinical samples by real-time polymerase chain reaction using a sepsis pathogen DNA detection kit Critical Care 14 159.
147. A.M. Frye C.A. Baker D.L. Rustvold K.A. Heath J. Hunt 2012 Clinical impact of a real-time PCR assay for rapid identification of staphylococcal bacteremia Journal of Clinical Microbiology 50 127 133.
148. K.A. Bauer J.E. West J.M. Balada-Llasat P. Pancholi K.B. Stevenson 2010 An antimicrobial stewardship program's impact with rapid polymerase chain reaction methicillin-resistant Staphylococcus aureus/S. aureus blood culture test in patients with S. aureus bacteremia Clinical Infectious Diseases: an official publication of the Infectious Diseases Society of America 51 1074 1080.
149. C. Holtzman D. Whitney T. Barlam N.S. Miller 2011 Assessment of impact of peptide nucleic acid fluorescence in situ hybridization for rapid identification of coagulase-negative staphylococci in the absence of antimicrobial stewardship intervention Journal of Clinical Microbiology 49 1581 1582.
150. E. Charani R. Edwards N. Sevdalis B. Alexandrou E. Sibley 2011 Behavior change strategies to influence antimicrobial prescribing in acute care: a systematic review Clinical Infectious Diseases: an official publication of the Infectious Diseases Society of America 53 651 662.
151. R.R. Roberts B. Hota I. Ahmad R.D. Scott S.D. Foster 2009 Hospital and societal costs of antimicrobial-resistant infections in a Chicago teaching hospital: implications for antibiotic stewardship Clinical Infectious Diseases: an official publication of the Infectious Diseases Society of America 49 1175 1184.
152. C.A. Haberland W.E. Benitz G.D. Sanders J.B. Pietzsch S. Yamada 2002 Perinatal screening for group B streptococci: cost-benefit analysis of rapid polymerase chain reaction Pediatrics 110 471 480.
153. H. Burchardi H. Schneider 2004 Economic aspects of severe sepsis: a review of intensive care unit costs, cost of illness and cost effectiveness of therapy PharmacoEconomics 22 793 813.
154. G.N. Forrest S. Mehta E. Weekes D.P. Lincalis J.K. Johnson 2006 Impact of rapid in situ hybridization testing on coagulase-negative staphylococci positive blood cultures The journal of Antimicrobial Chemotherapy 58 154 158.
155. L.E. Lehmann B. Herpichboehm G.J. Kost M.H. Kollef F. Stuber 2010 Cost and mortality prediction using polymerase chain reaction pathogen detection in sepsis: evidence from three observational trials Critical Care 14 186.
156. G. Forrest 2006 Role of antifungal susceptibility testing in patient management Current Opinion in Infectious Diseases 19 538 543.
157. E.L. Tsalik L.B. Jaggers S.W. Glickman R.J. Langley J.C. van Velkinburgh 2012 Discriminative value of inflammatory biomarkers for suspected sepsis The journal of Emergency Medicine 43 97 106.
158. M.W. Moyer 2012 New biomarkers sought for improving sepsis management and care Nature Medicine 18 999.
159. L. Su B. Han C. Liu L. Liang Z. Jiang 2012 Value of soluble TREM-1, procalcitonin, and C-reactive protein serum levels as biomarkers for detecting bacteremia among sepsis patients with new fever in intensive care units: a prospective cohort study BMC Infectious Diseases 12 157.
160. Y. Backes K.F. van der Sluijs D.P. Mackie F. Tacke A. Koch 2012 Usefulness of suPAR as a biological marker in patients with systemic inflammation or infection: a systematic review Intensive Care Medicine 38 1418 1428.
161. M. Al Shuaibi R.R. Bahu A.M. Chaftari I. Al Wohoush W. Shomali 2013 Pro-adrenomedullin as a novel biomarker for predicting infections and response to antimicrobials in febrile patients with hematologic malignancies Clinical Infectious Diseases: an official publication of the Infectious Diseases Society of America 56 943 950.
162. R.J. Langley E.L. Tsalik J.C. van Velkinburgh S.W. Glickman B.J. Rice 2013 An integrated clinico-metabolomic model improves prediction of death in sepsis Science Translational Medicine 5 195ra195.
163. Q. Zhang M. Raoof Y. Chen Y. Sumi T. Sursal 2010 Circulating mitochondrial DAMPs cause inflammatory responses to injury Nature 464 104 107.
164. A. Sutherland M. Thomas R.A. Brandon R.B. Brandon J. Lipman 2011 Development and validation of a novel molecular biomarker diagnostic test for the early detection of sepsis Critical Care 15 149.
165. L.A. Neely M. Audeh N.A. Phung M. Min A. Suchocki 2013 T2 magnetic resonance enables nanoparticle-mediated rapid detection of candidemia in whole blood Science Translational Medicine 5 182ra154.
166. B.H. Weigl C.A. Gaydos G. Kost F.R. Beyette S., Sabourin Jr. 2012 The value of clinical needs assessments for pointof-care diagnostics Point of Care 11 108 113.
167. G.J. Kost D.M. Mecozzi T.K. Brock C.M. Curtis 2012 Assessing point-of-care device specifications and needs for pathogen detection in emergencies and disasters Point of Care 11 119 125.
168. K.D. Leuthner G.V. Doern 2013 Antimicrobial Stewardship Programs Journal of Clinical Microbiology 51 3916 3920.
169. L. Hall K.M. Le Febre S.M. Deml S.L. Wohlfiel N.L. Wengenack 2012 Evaluation of the Yeast Traffic Light PNA FISH probes for identification of Candida species from positive blood cultures Journal of Clinical Microbiology 50 1446 1448.
170. P.G. Kelley E.A. Grabsch J. Farrell S. Xie J. Montgomery 2011 Evaluation of the Xpert MRSA/SA Blood Culture assay for the detection of Staphylococcus aureus including strains with reduced vancomycin susceptibility from blood culture specimens Diagnostic Microbiology and Infectious Disease 70 404 407.
171. J.M. Molina J. Cordoba P. Ramirez M. [ Gobernado 2008 Automatic detection of bacterial and fungal infections in blood Enfermedades Infecciosas y Microbiologia Clinica 26 9 S75 S80.
172. P. Gaibani G. Rossini S. Ambretti F. Gelsomino A.M. Pierro 2009 Blood culture systems: rapid detection — how and why International Journal of Antimicrobial Agents 34 4 S13 S15.
173. U. Lodes F. Meyer B. Konig H. [ Lippert 2009 Microbiological sepsis screening in surgical ICU patients with the “lightCycler” Septifast test — a pilot study Zentralblatt für Chirurgie 134 249 253.
174. J.R. Figueroa J. Ortiz I. Morales 2010 Use of the LightCycler SeptiFast test for rapid etiologic diagnosis of nosocomial infection in gynecological sepsis Gynecologic and Obstetric Investigation 70 215 216.
175. M. Avolio P. Diamante S. Zamparo M.L. Modolo S. Grosso 2010 Molecular identification of bloodstream pathogens in patients presenting to the emergency department with suspected sepsis Shock 34 27 30.
176. D. Maubon R. Hamidfar-Roy S. Courby A. Vesin M. Maurin 2010 Therapeutic impact and diagnostic performance of multiplex PCR in patients with malignancies and suspected sepsis The journal of Infection 61 335 342.
177. U. Lodes H. Lippert F. [ Meyer 2011 Molecular biological sepsis diagnostic using multiplex PCR in surgical intensive care as suitable alternative to conventional microbial culture — a representative overview Zentralblatt für Chirurgie 136 135 142.
178. D. Bravo J. Blanquer M. Tormo G. Aguilar R. Borras 2011 Diagnostic accuracy and potential clinical value of the LightCycler SeptiFast assay in the management of bloodstream infections occurring in neutropenic and critically ill patients International Journal of Infectious Diseases: IJID: official publication of the International Society for Infectious Diseases 15 326 331.
179. P. Dark G. Dunn P. Chadwick D. Young A. Bentley 2011 The clinical diagnostic accuracy of rapid detection of healthcare-associated bloodstream infection in intensive care using multipathogen real-time PCR technology BMJ Open 1 000181.
180. N.K. Tran D.H. Wisner T.E. Albertson S. Cohen D. Greenhalgh 2012 Multiplex polymerase chain reaction pathogen detection in patients with suspected septicemia after trauma, emergency, and burn surgery Surgery 151 456 463.
181. D.A. Popov T. [ Vostrikova 2011 The first experience of application of PCR techniques in real-time mode to diagnose bacteriemia during postoperational period in cardiosurgery patients 49 2 Klinicheskaia Laboratornaia Diagnostika.
182. S. Sancho-Tello D. Bravo R. Borras E. Costa B. Munoz-Cobo 2011 Performance of the LightCycler SeptiFast test Mgrade in detecting microbial pathogens in purulent fluids Journal of Clinical Microbiology 49 2988 2991.
183. J.C. Palomares S. Bernal M. Marin V.P. Holgado C. Castro 2011 Molecular diagnosis of Aspergillus fumigatus endocarditis Diagnostic Microbiology and Infectious Disease 70 534 537.
184. L. Martinez-Lamas M.L. Perez del Molino F. Pardo E. Varela B. [ Regueiro 2011 Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry vs conventional methods in the identification of Candida nonalbicans Enfermedades Infecciosas y Microbiologia Clinica 29 568 572.
185. A. Mencacci C. Leli A. Cardaccia P. Montagna A. Moretti 2011 Comparison of conventional culture with SeptiFast real-time PCR for microbial pathogen detection in clinical specimens other than blood Journal of Medical Microbiology 60 1774 1778.
186. A. Mencacci C. Leli A. Cardaccia M. Meucci A. Moretti 2012 Procalcitonin predicts real-time PCR results in blood samples from patients with suspected sepsis PloS One 7 53279.
187. P. Dark C. Wilson B. Blackwood D.F. McAuley G.D. Perkins 2012 Accuracy of LightCycler® SeptiFast for the detection and identification of pathogens in the blood of patients with suspected sepsis: a systematic review protocol BMJ Open 2 000392.
188. L. Dubska M. Vyskocilova D. Minarikova P. Jelinek R. Tejkalova 2012 LightCycler SeptiFast technology in patients with solid malignancies: clinical utility for rapid etiologic diagnosis of sepsis Critical Care 16 404.
189. L. Pasqualini A. Mencacci C. Leli P. Montagna A. Cardaccia 2012 Diagnostic performance of a multiple real-time PCR assay in patients with suspected sepsis hospitalized in an internal medicine ward Journal of Clinical Microbiology 50 1285 1288.
190. J.P. Lanoix J.L. Schmit Y. Douadi 2012 Bacterial lung sepsis in patients with febrile neutropenia Current Opinion in Pulmonary Medicine 18 175 180.
191. A. Mencacci C. Leli P. Montagna A. Cardaccia M. Meucci 2012 Diagnosis of infective endocarditis: comparison of the LightCycler SeptiFast real-time PCR with blood culture Journal of Medical Microbiology 61 881 883.
192. S. Ahmad Z. Khan 2012 Invasive candidiasis: a review of nonculture-based laboratory diagnostic methods Indian Journal of Medical Microbiology 30 264 269.
193. M.V. Mauro P. Cavalcanti D. Perugini A. Noto D. Sperli 2012 Diagnostic utility of LightCycler SeptiFast and procalcitonin assays in the diagnosis of bloodstream infection in immunocompromised patients Diagnostic Microbiology and Infectious Disease 73 308 311.
194. M. Paolucci M. Stanzani F. Melchionda G. Tolomelli G. Castellani 2013 Routine use of a real-time polymerase chain reaction method for detection of bloodstream infections in neutropaenic patients Diagnostic Microbiology and Infectious Disease 75 130 134.