Advertisement
Review Article| Volume 33, ISSUE 3, P413-437, September 2013

Laboratory Detection of Sepsis

Biomarkers and Molecular Approaches

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribers receive full online access to your subscription and archive of back issues up to and including 2002.

      Content published before 2002 is available via pay-per-view purchase only.

      Subscribe:

      Subscribe to Clinics in Laboratory Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Bone R.C.
        • Balk R.A.
        • Cerra F.B.
        • et al.
        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. 1992; 101: 1656-1662
        • Vincent J.L.
        Dear SIRS, I’m sorry to say that I don’t like you….
        Crit Care Med. 1997; 25: 372-374
        • Trzeciak S.
        • Zanotti-Cavazzoni S.
        • Parrillo J.E.
        • et al.
        Inclusion criteria for clinical trials in sepsis: did the American College of Chest Physicians/Society of Critical care Medicine consensus conference definitions of sepsis have an impact?.
        Chest. 2005; 127: 242-245
        • Levy M.M.
        • Fink M.P.
        • Marshall J.C.
        • et al.
        2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definition Conference.
        Crit Care Med. 2003; 31: 1250-1256
        • Howell M.D.
        • Talmor D.
        • Schuetz P.
        • et al.
        Proof of principle: the predisposition, infection, response, organ failure sepsis staging system.
        Crit Care Med. 2011; 39: 322-327
        • Angus D.C.
        • Linde-Zwirble W.T.
        • Lidicker J.
        • et al.
        Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care.
        Crit Care Med. 2001; 29: 1303-1310
        • Engel C.
        • Brunkhorst F.M.
        • Bone H.C.
        • et al.
        Epidemiology of sepsis in Germany: results from a national prospective multicenter study.
        Intensive Care Med. 2007; 33: 606-618
        • Vincent J.L.
        • Sakr Y.
        • Sprung C.L.
        • et al.
        Sepsis in European intensive care units: results of the SOAP study.
        Crit Care Med. 2006; 34: 344-353
        • Hoyert D.L.
        • Xu J.
        Deaths: preliminary data for 2011.
        Natl Vital Stat Rep. 2012; 61: 1-65
        • Diekema D.J.
        • Beekmann S.E.
        • Chapin K.C.
        • et al.
        Epidemiology and outcome of nosocomial and community-acquired bloodstream infection.
        J Clin Microbiol. 2003; 41: 3655-3660
        • Martin G.S.
        • Mannino D.M.
        • Eaton S.
        • et al.
        The epidemiology of sepsis in the United States from 1979 through 2000.
        N Engl J Med. 2003; 348: 1546-1554
        • Finfer S.
        • Bellomo R.
        • Lipman J.
        • et al.
        Adult-population incidence of severe sepsis in Australian and New Zealand intensive care units.
        Intensive Care Med. 2004; 30: 589-596
        • Harrison D.A.
        • Welch C.A.
        • Eddleston J.M.
        The epidemiology of severe sepsis in England, Wales and Northern Ireland, 1996-2004: secondary analysis of a high quality clinical database, the ICNARC case mix programme database.
        Crit Care. 2006; 10: R42
        • Levy M.M.
        • Dellinger R.P.
        • Townsend S.R.
        • et al.
        The surviving sepsis campaign: results of an international guideline-based performance improvement program targeting severe sepsis.
        Crit Care Med. 2010; 38: 367-374
        • Hall M.J.
        • Williams S.N.
        • DeFrances C.J.
        • et al.
        Inpatient care for septicemia or sepsis: a challenge for patients and hospitals.
        NCHS Data Brief. 2011; (National Center for Health Statistics, Hyattsville (MD)): 1-8
        • Moore L.J.
        • Moore F.A.
        Epidemiology of sepsis in surgical patients.
        Surg Clin North Am. 2012; 92: 1425-1443
        • McBean M.
        • Rajamani S.
        Increasing rates of hospitalization due to septicemia in the US elderly population, 1986-1997.
        J Infect Dis. 2001; 183: 596-603
        • Baine W.B.
        • Yu W.
        • Summe J.P.
        The epidemiology of hospitalization of elderly Americans for septicemia or bacteremia in 1991-1998: application of Medicare claims data.
        Ann Epidemiol. 2001; 11: 118-126
        • Burchardi H.
        • Schneider H.
        Economic aspects of severe sepsis.
        Pharmacoeconomics. 2004; 22: 793-813
        • Dellinger R.P.
        • Levy M.M.
        • Carlet J.M.
        • et al.
        Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock.
        Crit Care Med. 2008; 36: 296-327
        • Magadia R.R.
        • Weinstein M.P.
        Laboratory diagnosis of bacteremia and fungemia.
        Infect Dis Clin North Am. 2001; 15: 1009-1024
        • Riedel S.
        • Carroll K.C.
        Blood cultures: key elements for best practices and future directions.
        J Infect Chemother. 2010; 16: 301-316
        • Schifman A.B.
        • Strand C.L.
        • Meier F.A.
        • et al.
        Blood culture contamination: a College of American Pathologists Q-Probes study involving 640 institutions and 497134 specimens from adult patients.
        Arch Pathol Lab Med. 1998; 122: 216-221
        • Lee C.C.
        • Lin W.J.
        • Shih H.I.
        • et al.
        Clinical significance of potential contaminants in blood cultures among patients in a medical center.
        J Microbiol Immunol Infect. 2007; 40: 438-444
        • Tokars J.I.
        Predictive value of blood cultures positive for coagulase-negative staphylococci: implications for patient care and health care quality assurance.
        Clin Infect Dis. 2004; 39: 333-341
        • Lee A.
        • Mirrett S.
        • Reller L.B.
        • et al.
        Detection of bloodstream infection in adults: how many blood cultures are needed?.
        J Clin Microbiol. 2007; 45: 3546-3548
        • Bates D.W.
        • Cook E.F.
        • Goldman L.
        • et al.
        Predicting bacteremia in hospitalized patients: a prospective validated model.
        Ann Intern Med. 1990; 113: 495-500
        • Roth A.
        • Wiklund A.E.
        • Palsson A.S.
        • et al.
        Reducing blood culture contamination by a simple informational intervention.
        J Clin Microbiol. 2010; 48: 4552-4558
        • Bone R.C.
        Sir Isaac Newton, sepsis, SIRS, and CARS.
        Crit Care Med. 1996; 24: 1125-1128
        • Ward N.S.
        • Casserly B.
        • Ayala A.
        The compensatory anti-inflammatory response syndrome (CARS) in critically ill patients.
        Clin Chest Med. 2008; 29: 617-625
        • Volk H.D.
        • Reinke P.
        • Docke W.D.
        Clinical aspects: from systemic inflammation to “immuneparalysis”.
        Chem Immunol. 2000; 74: 162-177
        • Wolk K.
        • Docke W.D.
        • von Baehr V.
        • et al.
        Impaired antigen presentation by human monocytes during endotoxin tolerance.
        Blood. 2000; 96: 218-223
        • Hotchkiss R.S.
        • Karl I.E.
        The pathophysiology and treatment of sepsis.
        N Engl J Med. 2003; 348: 138-150
        • Remick D.G.
        Biological perspectives: pathophysiology of sepsis.
        Am J Pathol. 2007; 170: 1435-1444
        • Rittirsch D.
        • Flierl M.
        • Ward P.A.
        Harmful molecular mechanisms in sepsis.
        Nat Rev Immunol. 2008; 8: 776-787
        • Boomer J.S.
        • To K.
        • Chang K.C.
        • et al.
        Immunosuppression in patients who die of sepsis and multiple organ failure.
        JAMA. 2011; 306: 2594-2605
        • Biomarkers Definitions Working Group, Bethesda, MD
        Biomarkers and surrogate endpoints: preferred definitions and conceptual framework.
        Clin Pharmacol Ther. 2001; 69: 89-95
        • Marshall J.C.
        • Reinhart K.
        • International Sepsis Forum
        Biomarkers of sepsis.
        Crit Care Med. 2009; 37: 2290-2298
        • Limper M.
        • de Kruif M.D.
        • Duits A.J.
        • et al.
        The diagnostic role of procalcitonin and other biomarkers in discriminating infectious from non-infectious fever.
        J Infect. 2010; 60: 409-416
        • Marshall J.C.
        • Vincent J.L.
        • Mitchell P.F.
        • et al.
        Measures, markers, and mediators: toward a staging system for clinical sepsis: a report of the Fifth Toronto Sepsis Roundtable, Ontario, Canada, October 25–26, 2000.
        Crit Care Med. 2003; 31: 1560-1567
        • Simon L.
        • Gauvin F.
        • Amre D.K.
        • et al.
        Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis.
        Clin Infect Dis. 2004; 39: 206-217
        • Vincent J.L.
        • Donadello K.
        • Schmidt X.
        Biomarkers in the critically ill patient: C-reactive protein.
        Crit Care Clin. 2011; 27: 241-251
        • Timonen T.T.
        • Koistinen P.
        C-reactive protein for detection and follow-up of bacterial and fungal infections in severely neutropenic patients with acute leukemia.
        Eur J Cancer Clin Oncol. 1985; 21: 557-562
        • Flood R.G.
        • Badik J.
        • Aronoff S.C.
        The utility of serum C-reactive protein in differentiating bacterial from nonbacterial pneumonia in children: a meta-analysis of 1230 children.
        Pediatr Infect Dis J. 2008; 27: 95-99
        • Lannergard A.
        • Friman G.
        • Ewald U.
        • et al.
        Serum amyloid A (SAA) protein and high-sensitivity C-reactive protein (hsCRP) in healthy newborn infants and healthy young through elderly adults.
        Acta Paediatr. 2005; 94: 1198-1202
        • Povoa P.
        • Coelho L.
        • Almeida E.
        • et al.
        C-reactive protein as a marker of infection in critically ill patients.
        Clin Microbiol Infect. 2005; 11: 101-108
        • Ho K.M.
        • Lipman J.
        An update on C-reactive protein for intensivists.
        Anaesth Intensive Care. 2009; 37: 234-241
        • Martini A.
        • Gottin L.
        • Melot C.
        • et al.
        A prospective evaluation of the Infection Probability Score (IPS) in the intensive care unit.
        J Infect. 2008; 56: 313-318
        • Povoa P.
        • Coelho L.
        • Almeida E.
        • et al.
        Early identification of intensive care unit-acquired infections with daily monitoring of C-reactive protein: a prospective observational study.
        Crit Care. 2006; 10: R63
        • Silvestre J.
        • Povoa P.
        • Coelho L.
        • et al.
        Is C-reactive protein a good prognostic marker in septic patients?.
        Intensive Care Med. 2009; 35: 909-913
        • Reny J.L.
        • Vuagnat A.
        • Ract C.
        • et al.
        Diagnosis and follow-up of infections in intensive care patients: value of C-reactive protein compared with other clinical and biological variables.
        Crit Care Med. 2002; 30: 529-535
        • Schmidt X.
        • Vincent J.L.
        The time course of blood C-reactive protein concentrations in relation to the response to initial antimicrobial therapy in patients with sepsis.
        Infection. 2008; 36: 213-219
        • Riedel S.
        Procalcitonin and the role of biomarkers in the diagnosis and management of sepsis.
        Diagn Microbiol Infect Dis. 2012; 73: 221-227
        • Assicot M.
        • Gendrel D.
        • Carsin H.
        • et al.
        High serum procalcitonin concentrations in patients with sepsis and infection.
        Lancet. 1993; 341: 515-518
        • Linscheid P.
        • Seboek D.
        • Nylen E.S.
        • et al.
        In vitro and in vivo calcitonin I gene expression in parenchymal cells: a novel product of human adipose tissue.
        Endocrinology. 2003; 144: 5578-5584
        • Mueller B.
        • White J.C.
        • Nylen E.S.
        • et al.
        Ubiquitous expression of the calcitonin I gene in multiple tissues in response to sepsis.
        J Clin Endocrinol Metab. 2001; 86: 396-404
        • Becker K.L.
        • Nylen E.S.
        • White J.C.
        • et al.
        Procalcitonin and the calcitonin gene family of peptides in inflammation, infection, and sepsis: a journey from calcitonin back to its precursors.
        J Clin Endocrinol Metab. 2004; 89: 1512-1525
        • Mueller B.
        • Peri G.
        • Doni A.
        • et al.
        High circulating levels of the IL-1 type II decoy receptor in critically ill patients with sepsis: association of high decoy receptor levels with glucocorticoid administration.
        J Leukoc Biol. 2002; 72: 643-649
        • Mueller F.
        • Christ-Crain M.
        • Bregenzer T.
        • et al.
        Procalcitonin levels predict bacteremia in patients with community-acquired pneumonia: a prospective cohort trial.
        Chest. 2010; 138: 121-129
        • De Kruif M.
        • Limper M.
        • Gerritsen H.
        • et al.
        Additional value of procalcitonin for diagnosis of infection in patients with fever at the emergency department.
        Crit Care Med. 2010; 38: 457-463
        • Riedel S.
        • Melendez J.H.
        • An A.T.
        • et al.
        Procalcitonin as a marker for the detection of bacteremia and sepsis in the emergency department.
        Am J Clin Pathol. 2011; 135: 182-189
        • Lai C.C.
        • Chen S.Y.
        • Wang C.Y.
        • et al.
        Diagnostic value of procalcitonin for bacterial infection in elderly patients in the emergency department.
        J Am Geriatr Soc. 2010; 58: 518-522
        • Fioretto J.R.
        • Martin J.G.
        • Kurokawa C.S.
        • et al.
        Comparison between procalcitonin and C-reactive protein for early diagnosis of children with sepsis and septic shock.
        Inflamm Res. 2010; 59: 581-586
        • Schuetz P.
        • Mueller B.
        • Trampuz A.
        Serum procalcitonin for discrimination of blood contamination from bloodstream infection due to coagulase-negative staphylococci.
        Infection. 2007; 35: 352-355
        • Jones A.E.
        • Fiechtl J.F.
        • Brown M.D.
        • et al.
        Procalcitonin test in the diagnosis of bacteremia: a meta-analysis.
        Ann Emerg Med. 2007; 50: 34-41
        • Tang B.M.
        • Eslick G.D.
        • Craig J.C.
        • et al.
        Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis.
        Lancet Infect Dis. 2007; 7: 210-217
        • Uzzan B.
        • Cohen R.
        • Nicolas P.
        • et al.
        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. 2006; 34: 1996-2003
        • Kibe S.
        • Adams K.
        • Barlow G.
        Diagnostic and prognostic biomarkers of sepsis in critical care.
        J Antimicrob Chemother. 2011; 66: 33-40
        • Ruiz-Alvarez M.J.
        • Garcia-Valdecasas S.
        • De Pablo R.
        • et al.
        Diagnostic efficacy and prognostic value of serum procalcitonin concentration in patients with suspected sepsis.
        J Intensive Care Med. 2009; 24: 63-71
        • Nobre V.
        • Harbath S.
        • Graf J.D.
        • et al.
        Use of procalcitonin to shorten antibiotic treatment duration in septic patients.
        Am J Respir Crit Care Med. 2008; 177: 498-505
        • Agarwal R.
        • Schwartz D.N.
        Procalcitonin to guide duration of antimicrobial therapy in intensive care units: a systematic review.
        Clin Infect Dis. 2011; 53: 379-387
        • Schuetz P.
        • Chiappa V.
        • Briel M.
        • et al.
        Procalcitonin algorithms for antibiotic therapy decisions: a systematic review of randomized controlled trials and recommendations for clinical algorithms.
        Arch Intern Med. 2011; 171: 1322-1331
        • Tobias P.S.
        • Mathison J.
        • Mintz D.
        • et al.
        Participation of lipopolysaccharide-binding protein in lipopolysaccharide-dependent macrophage activation.
        Am J Respir Cell Mol Biol. 1992; 7: 239-245
        • Wurfel M.M.
        • Kunitake S.T.
        • Lichenstein H.
        • et al.
        Lipopolysaccharide (LPS)-binding protein is carried on lipoproteins and acts as a cofactor in the neutralization of LPS.
        J Exp Med. 1994; 180: 1025-1035
        • Worthen G.S.
        • Avdi N.
        • Vukajlovich S.
        • et al.
        Neutrophil adherence induced by lipopolysaccharide in vitro. Role of plasma component interaction with lipopolysaccharide.
        J Clin Invest. 1992; 90: 2526-2535
        • Mathison J.
        • Tobias P.S.
        • Wolfson E.
        • et al.
        Plasma lipopolysaccharide (LPS)-binding protein. A key component in macrophage recognition of gram-negative LPS.
        J Immunol. 1992; 149: 200-206
        • Opal S.M.
        • Scannon P.J.
        • Vincent J.L.
        • et al.
        Relationship between plasma levels of lipopolysaccharide (LPS) and LPS-binding protein in patients with severe sepsis and septic shock.
        J Infect Dis. 1999; 180: 1584-1589
        • Gaini S.
        • Koldkjaer O.G.
        • Pedersen C.
        • et al.
        Procalcitonin, lipopolysaccharide-binding protein, interleukin-6 and C-reactive protein in community-acquired infections and sepsis: a prospective study.
        Crit Care. 2006; 10: R53
        • Tschaikowsky K.
        • Hedwig-Geissing M.
        • Schmidt J.
        • et al.
        Lipopolysaccharide-binding protein for monitoring of post-operative sepsis: complemental to C-reactive protein or redundant?.
        PLoS One. 2011; 6: e23615
        • Villar J.
        • Perez-Mendez L.
        • Espinosa E.
        • et al.
        Serum lipopolysaccharide-binding protein levels predict severity of lung injury and mortality in patients with severe sepsis.
        PLoS One. 2009; 4: e6818
        • Sakr Y.
        • Burgett U.
        • Nacul F.E.
        • et al.
        Lipopolysaccharide binding protein in a surgical intensive care unit: a marker of sepsis?.
        Crit Care Med. 2008; 36: 2014-2022
        • Hollenberg S.M.
        • Ahrens T.S.
        • Annane D.
        • et al.
        Practice parameters for hemodynamic support of sepsis in adult patients: 2004 update.
        Crit Care Med. 2004; 32: 1928-1948
        • Treschan T.A.
        • Peters J.
        The vasopressin system: physiology and clinical strategies.
        Anesthesiology. 2006; 105: 599-612
        • Sharshar T.
        • Blanchard A.
        • Paillard M.
        • et al.
        Circulating vasopressin levels in septic shock.
        Crit Care Med. 2003; 31: 1752-1758
        • Hinson J.P.
        • Kapas S.
        • Smith D.M.
        Adrenomedullin, a multifunctional regulatory peptide.
        Endocr Rev. 2000; 21: 138-167
        • Hirata Y.
        • Mitaka C.
        • Sato K.
        • et al.
        Increased circulating adrenomedullin, a novel vasodilatory peptide, in sepsis.
        J Clin Endocrinol Metab. 1996; 81: 1449-1453
        • Wang P.
        • Ba Z.F.
        • Cioffi W.G.
        • et al.
        The pivotal role of adrenomedullin in producing hyperdynamic circulation during the early stage of sepsis.
        Arch Surg. 1998; 133: 1298-1304
        • Ornan D.A.
        • Chaudry I.A.
        • Wang P.
        Pulmonary clearance of adrenomedullin is reduced during the late stage of sepsis.
        Biochim Biophys Acta. 1999; 1427: 315-321
        • Ueda S.
        • Nishio K.
        • Minamino N.
        • et al.
        Increased plasma levels of adrenomedullin in patients with systemic inflammatory response syndrome.
        Am J Respir Crit Care Med. 1999; 160: 132-136
        • Christ-Crain M.
        • Morgenthaler N.G.
        • Struck J.
        • et al.
        Mid-regional pro-adrenomedullin as a prognostic marker in sepsis: an observational study.
        Crit Care. 2005; 9: R816-R824
        • Guignant C.
        • Voirin N.
        • Venet F.
        • et al.
        Assessment of pro-vasopressin and pro-adrenomedullin as predictors of 28-day mortality in septic shock patients.
        Intensive Care Med. 2009; 35: 1859-1867
        • Travaglino F.
        • De Berardinis B.
        • Magrini L.
        • et al.
        Utility of procalcitonin (PCT) and mid regional pro-adrenomedullin (MR-proADM) in risk stratification of critically ill febrile patients in emergency department (ED). A comparison with APACHE II score.
        BMC Infect Dis. 2012; 12: 184
        • Angeletti S.
        • Battistoni F.
        • Fioravanti M.
        • et al.
        Procalcitonin and mid-regional pro-adrenomedullin test combination in sepsis diagnosis.
        Clin Chem Lab Med. 2012; ([Epub ahead of print])https://doi.org/10.1515/cclm-2012-0595
        • Kuster H.
        • Weiss M.
        • Willeitner A.E.
        • et al.
        Interleukin-1 receptor antagonist and interleukin-6 for early diagnosis of neonatal sepsis 2 days before clinical manifestation.
        Lancet. 1998; 352: 1271-1277
        • Uusitalo-Seppala R.
        • Koskinen P.
        • Leino A.
        • et al.
        Early detection of severe sepsis in the emergency room: diagnostic value of C-reactive protein, procalcitonin, and interleukin-6.
        Scand J Infect Dis. 2011; 43: 883-890
        • Rice T.W.
        • Wheeler A.P.
        • Bernard G.W.
        • et al.
        A randomized, double-blind, placebo-controlled trial of TAK-242 for the treatment of severe sepsis.
        Crit Care Med. 2010; 38: 1685-1694
        • Urbonas V.
        • Eidukaite A.
        • Tamuliene I.
        The diagnostic value of interleukin-6 and interleukin-8 for early prediction of bacteremia and sepsis in children with febrile neutropenia and cancer.
        J Pediatr Hematol Oncol. 2012; 34: 122-127
        • Andaluz-Ojeda D.
        • Bobillo F.
        • Iglesias V.
        • et al.
        A combined score of pro- and anti-inflammatory interleukins improves mortality prediction in severe sepsis.
        Cytokine. 2012; 57: 332-336
        • Wong H.R.
        • Cvijanovich N.Z.
        • Hall M.
        • et al.
        Interleukin-27 is a novel candidate diagnostic biomarker for bacterial infection in critically ill children.
        Crit Care. 2012; 16: R213
        • Mauri T.
        • Bellani G.
        • Patroniti N.
        • et al.
        Persisting high levels of plasma pentraxin 3 over the first days after severe sepsis and septic shock onset are associated with mortality.
        Intensive Care Med. 2010; 36: 621-629
        • deKriuf M.D.
        • Limper M.
        • Sierhuis K.
        • et al.
        PTX3 predicts severe disease in febrile patients in the emergency department.
        J Infect. 2010; 60: 122-127
        • Romaschin A.D.
        • Harris D.M.
        • Ribeiro M.B.
        • et al.
        A rapid assay of endotoxin in whole blood using autologous neutrophil dependent chemiluminescence.
        J Immunol Methods. 1998; 212: 169-185
        • Marshall J.C.
        • Foster D.
        • Vincent J.L.
        • et al.
        Diagnostic and prognostic implications of endotoxemia in critical illness: results of the MEDIC study.
        J Infect Dis. 2004; 190: 527-534
        • Yaguchi A.
        • Yuzawa J.
        • Klein D.J.
        • et al.
        Combining intermediate levels of the endotoxin activity assay (EAA) with other biomarkers in the assessment of patients with sepsis: results of an observational study.
        Crit Care. 2012; 16: R88
        • Ventetuolo C.E.
        • Levy M.M.
        Biomarkers: diagnosis and risk assessment in sepsis.
        Clin Chest Med. 2008; 29: 591-603
        • Casserly B.
        • Read R.
        • Levy M.M.
        Multimarker panels in sepsis.
        Crit Care Clin. 2011; 27: 391-405
        • Tromp M.
        • Lansdorp B.
        • Bleeker-Rovers C.P.
        • et al.
        Serial and panel analyses of biomarkers do not improve the prediction of bacteremia compared to one procalcitonin measurement.
        J Infect. 2012; 65: 292-301
        • Stamper P.S.
        • Cai M.
        • Howard T.
        • et al.
        Clinical validation of the molecular-based BD GeneOhmTM StaphSR for the direct detection of Staphylococcus aureus and methicillin resistant Staphylococcus aureus in positive blood cultures.
        J Clin Microbiol. 2007; 45: 2191-2196
        • Grobner S.
        • Dion M.
        • Plante M.
        • et al.
        Evaluation of the BD GeneOhm StaphSR assay for detection of methicillin resistant and methicillin-susceptible Staphylococcus aureus isolates from spiked positive blood culture bottles.
        J Clin Microbiol. 2009; 47: 1689-1694
        • Snyder J.W.
        • Munier G.K.
        • Heckman S.A.
        • et al.
        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.
        J Clin Microbiol. 2009; 47: 3747-3748
        • Stamper P.D.
        • Louie L.
        • Wong H.
        • et al.
        Genotypic and phenotypic characterization of methicillin-susceptible Staphylococcus aureus isolates misidentified as methicillin-resistant Staphylococcus aureus by the BD GeneOhm MRSA assay.
        J Clin Microbiol. 2011; 49: 1240-1244
        • Munson E.
        • Kramme T.
        • Culver A.
        • et al.
        Cost effective modification of a commercial PCR-assay for detection of methicillin-resistant/susceptible Staphylococcus aureus from positive blood cultures.
        J Clin Microbiol. 2010; 48: 1408-1412
        • Wolk D.M.
        • Struelens M.J.
        • Pancholi P.
        • et al.
        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 cultures assays.
        J Clin Microbiol. 2009; 47: 823-826
        • Spencer D.H.
        • Sellenriek P.
        • Burnham C.A.
        Validation and implementation of the GeneXpert MRSA/SA blood culture assay in a pediatric setting.
        Am J Clin Pathol. 2011; 136: 690-694
        • Kelley P.G.
        • Grabsch E.A.
        • Farrell J.
        • et al.
        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.
        Diagn Microbiol Infect Dis. 2012; 70: 404-407
        • Biendo M.
        • Mammeri H.
        • Pluquet E.
        • et al.
        Value of Xpert MRSA/SA blood culture assay on the GeneXpert Dx system for rapid detection of Staphylococcus aureus and coagulase-negative staphylococci in patients with staphylococcal bacteremia.
        Diagn Microbiol Infect Dis. 2013; 75: 139-143
        • Parta M.
        • Goebel M.
        • Thomas J.
        • et al.
        Impact of an assay that enables rapid determination of Staphylococcus species and their drug susceptibility on the treatment of patients with positive blood culture results.
        Infect Control Hosp Epidemiol. 2010; 31: 1043-1048
        • Liberto M.C.
        • Puccio R.
        • Matera G.
        • et al.
        Applications of LightCycler Staphylococcus M-GRADE assay to detect Staphylococcus aureus and coagulase-negative staphylococci in clinical samples and in blood culture bottles.
        Infez Med. 2006; 14: 71-76
        • Shrestha N.K.
        • Tuohy M.J.
        • Padmanabhan R.A.
        • et al.
        Evaluation of the LightCycler Staphylococcus M GRADE kits on positive blood cultures that contained gram-positive cocci in clusters.
        J Clin Microbiol. 2005; 43: 6144-6146
        • Ozen N.S.
        • Ogunc D.
        • Mutlu D.
        • et al.
        Comparison of four methods for rapid identification of Staphylococcus aureus from BACTEC 9240 blood culture system.
        Indian J Med Microbiol. 2011; 29: 42-46
        • Tang Y.W.
        • Kilic A.
        • Yang Q.
        • et al.
        StaphPlex System for rapid and simultaneous identification of antibiotic resistance determinants and Panton-Valentine leukocidin detection of staphylococci from positive blood cultures.
        J Clin Microbiol. 2007; 45: 1867-1873
      1. Nanosphere product [package insert]. 2012. Verigene Gram-Positive Blood Culture Nucleic Acid Test (BC-GP) Nanosphere, Inc. Northbrook, IL.

        • Mancini N.
        • Clerici N.
        • Diotti R.
        • et al.
        Molecular diagnosis of sepsis in neutropenic patients with haematological malignancies.
        J Med Microbiol. 2008; 57: 601-604
        • Gaibani P.
        • Rossini G.
        • Ambretti S.
        • et al.
        Blood culture systems: rapid detection–how and why?.
        Int J Antimicrob Agents. 2009; 34: S13-S15
        • Tissari P.
        • Zumla A.
        • Tarkka E.
        • et al.
        Accurate and rapid identification of bacterial species from positive blood cultures with a DNA-based microarray platform: an observational study.
        Lancet. 2010; 375: 224-230
        • Wellinghausen N.
        • Wirths B.
        • Essig A.
        • et al.
        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.
        J Clin Microbiol. 2004; 42: 3147-3152
        • Wallet F.
        • Nseir S.
        • Baumann L.
        • et al.
        Preliminary clinical study using a multiplex real-time PCR test for the detection of bacterial and fungal DNA directly in blood.
        Clin Microbiol Infect. 2010; 16: 774-779
        • Bravo D.
        • Blanquer J.
        • Tormo M.
        • et al.
        Diagnostic accuracy and potential clinical value of the LightCycler SeptiFast assay in the management of bloodstream infections occurring in neutropenic and critically ill patients.
        Int J Infect Dis. 2011; 15: e326-e331
        • Lucignano B.
        • Ranno S.
        • Liessenfeld O.
        • et al.
        Multiplex PCR allows rapid and accurate diagnosis of bloodstream infections in newborns and children with suspected sepsis.
        J Clin Microbiol. 2011; 49: 2252-2258
        • Wellinghausen N.
        • Kochem A.J.
        • Disqué C.
        • et al.
        Diagnosis of bacteremia in whole-blood samples by use of a commercial universal 16S rRNA gene-based PCR and sequence analysis.
        J Clin Microbiol. 2009; 47: 2759-2765
        • Kuhn C.
        • Disque C.
        • Muhl H.
        • et al.
        Evaluation of commercial universal rRNA gene PCR plus sequencing tests for identification of bacteria and fungi associated with infectious endocarditis.
        J Clin Microbiol. 2011; 49: 2919-2923
        • Mancini N.
        • Carletti S.
        • Ghidoli N.
        • et al.
        The era of molecular and other non-culture based methods in diagnosis of sepsis.
        Clin Microbiol Rev. 2010; 23: 235-251
        • Fitting C.
        • Parlato M.
        • Adib-Conquy M.
        • et al.
        DNAemia detection by multiplex PCR and biomarkers for infection in systemic inflammatory response syndrome patients.
        PLoS One. 2012; 7: 338916
        • Ecker D.J.
        • Sampath R.
        • Li H.
        • et al.
        New technology for rapid molecular diagnosis of bloodstream infections.
        Expert Rev Mol Diagn. 2010; 10: 399-415
        • Kaleta E.J.
        • Clark A.E.
        • Johnson D.R.
        • et al.
        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. 2011; 49: 345-353
        • Eshoo M.W.
        • Crowder C.D.
        • Li H.
        • et al.
        Detection and identification of Ehrlichia species in blood by use of PCR and electrospray ionization mass spectrometry.
        J Clin Microbiol. 2010; 48: 472-478
        • Bachmann L.M.
        • Juni P.
        • Reichenbach S.
        • et al.
        Consequences of different diagnostic “gold standards” in test accuracy research: carpal tunnel syndrome as an example.
        Int J Epidemiol. 2005; 34: 953-955
        • Marshall J.C.
        Sepsis: rethinking the approach to clinical research.
        J Leukoc Biol. 2008; 83: 471-482