title: Molecular microbiological methods in the diagnosis of neonatal sepsis.
abstract: Neonatal sepsis is a major cause of neonatal mortality and morbidity. The current gold standard for diagnosis of sepsis, namely blood culture, suffers from low sensitivity and a reporting delay of approximately 48-72 h. Rapid detection of sepsis and institution of antimicrobial therapy may improve patient outcomes. Rapid and sensitive tests that can inform clinicians regarding the institution or optimization of antimicrobial therapy are urgently needed. The ideal diagnostic test should have adequate specificity and negative predictive value to reliably exclude sepsis and avoid unnecessary antibiotic therapy. We comprehensively searched for neonatal studies that evaluated molecular methods for diagnosis of sepsis. We identified 19 studies that were assessed with respect to assay methodology and diagnostic characteristics. In addition, we also reviewed newer molecular microbiological assays of relevance that have not been fully evaluated in neonates. Molecular methods offer distinct advantages over blood cultures, including increased sensitivity and rapid diagnosis. However, diagnostic accuracy and cost-effectiveness should be established before implementation in clinical practice.
authors.affiliation: Section of Neonatology, Department of Pediatrics, Texas Children's Hospital & Baylor College of Medicine, 6621 Fannin St, Houston, TX 77030, USA. mohanv@bcm.edu
authors.forename: Mohan
authors.initials: M
authors.lastname: Venkatesh
authors.forename: Angela
authors.initials: A
authors.lastname: Flores
authors.forename: Ruth Ann
authors.initials: RA
authors.lastname: Luna
authors.forename: James
authors.initials: J
authors.lastname: Versalovic
mesh_terms: D001419:Bacteria / Q000235:genetics / Q000302:isolation & purification*; D002175:Candida / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D007231:Infant, Newborn; D025202:Molecular Diagnostic Techniques; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D016133:Polymerase Chain Reaction / Q000379:methods; D018805:Sepsis / Q000175:diagnosis* / Q000382:microbiology
references.citation: Anal Chem. 2003 Jan 15;75(2):261-7
references.pmid: 12553760
references.citation: J Mol Diagn. 2005 Nov;7(5):575-81
references.pmid: 16258155
references.citation: Eur J Clin Microbiol Infect Dis. 2003 Sep;22(9):558-60
references.pmid: 12938011
references.citation: J Clin Microbiol. 2006 Sep;44(9):3381-3
references.pmid: 16954279
references.citation: Curr Opin Infect Dis. 2006 Jun;19(3):290-7
references.pmid: 16645492
references.citation: J Med Microbiol. 2009 Apr;58(Pt 4):533-534
references.pmid: 19273654
references.citation: APMIS. 2000 May;108(5):385-92
references.pmid: 10937778
references.citation: Indian Pediatr. 2005 Jul;42(7):681-5
references.pmid: 16085969
references.citation: Ther Clin Risk Manag. 2008 Jun;4(3):637-40
references.pmid: 18827860
references.citation: J Pediatr. 1996 Aug;129(2):275-8
references.pmid: 8765627
references.citation: BMC Infect Dis. 2009 Aug 11;9:126
references.pmid: 19671147
references.citation: Methods Mol Biol. 2009;551:71-87
references.pmid: 19521868
references.citation: J Clin Microbiol. 2006 Jul;44(7):2389-97
references.pmid: 16825354
references.citation: J Clin Microbiol. 2003 Nov;41(11):5127-33
references.pmid: 14605149
references.citation: Curr Pharm Des. 2008;14(24):2439-44
references.pmid: 18781993
references.citation: Diagn Microbiol Infect Dis. 2008 Aug;61(4):446-52
references.pmid: 18501547
references.citation: Science. 1999 May 21;284(5418):1308-10
references.pmid: 10334977
references.citation: Diagn Microbiol Infect Dis. 2003 Oct;47(2):407-14
references.pmid: 14522514
references.citation: BMC Pediatr. 2009 Jan 19;9:5
references.pmid: 19152691
references.citation: Acta Paediatr. 2006 Oct;95(10):1218-23
references.pmid: 16982493
references.citation: J Mol Diagn. 2005 Feb;7(1):105-10
references.pmid: 15681481
references.citation: J Clin Microbiol. 2000 Jul;38(7):2574-8
references.pmid: 10878046
references.citation: J Mol Diagn. 2006 Jul;8(3):357-63
references.pmid: 16825509
references.citation: J Microbiol Methods. 2007 Mar;68(3):468-77
references.pmid: 17141897
references.citation: J Infect Chemother. 2009 Feb;15(1):23-6
references.pmid: 19280296
references.citation: Pediatr Infect Dis J. 2007 Nov;26(11):1064-6
references.pmid: 17984819
references.citation: Crit Care Med. 2009 Aug;37(8):2441-7
references.pmid: 19531943
references.citation: Acta Paediatr. 2001 Feb;90(2):179-83
references.pmid: 11236048
references.citation: Pediatrics. 2002 Aug;110(2 Pt 1):285-91
references.pmid: 12165580
references.citation: J Appl Microbiol. 2008 Apr;104(4):1228-37
references.pmid: 18028360
references.citation: J Clin Lab Anal. 2007;21(4):244-8
references.pmid: 17621359
references.citation: J Clin Microbiol. 2000 May;38(5):1753-7
references.pmid: 10790093
references.citation: Pediatr Res. 2005 Jul;58(1):143-8
references.pmid: 15985688
references.citation: Clin Microbiol Infect. 2009 Jun;15(6):544-51
references.pmid: 19392905
references.citation: J Clin Microbiol. 2008 Feb;46(2):713-20
references.pmid: 18077626
references.citation: J Med Microbiol. 2006 Nov;55(Pt 11):1505-1509
references.pmid: 17030909
references.citation: Neonatology. 2009;96(2):102-8
references.pmid: 19279393
references.citation: J Clin Microbiol. 2007 Sep;45(9):2985-92
references.pmid: 17652476
references.citation: J Med Microbiol. 2008 Mar;57(Pt 3):296-303
references.pmid: 18287291
references.citation: J Antimicrob Chemother. 2006 Jul;58(1):154-8
references.pmid: 16636084
references.citation: J Clin Microbiol. 2003 Jan;41(1):324-9
references.pmid: 12517868
references.citation: Int J Antimicrob Agents. 2007 Nov;30 Suppl 1:S7-15
references.pmid: 17707613
references.citation: Med Mycol. 2009;47 Suppl 1:S241-7
references.pmid: 19253138
references.citation: Microbiol Rev. 1987 Jun;51(2):221-71
references.pmid: 2439888
references.citation: Clin Microbiol Infect. 2006 Aug;12(8):745-53
references.pmid: 16842569
references.citation: J Clin Microbiol. 2002 Jul;40(7):2659-61
references.pmid: 12089301
references.citation: BMC Microbiol. 2009 Jan 03;9:1
references.pmid: 19121223
references.citation: J Pediatr. 1996 Feb;128(2):190-5
references.pmid: 8636810
references.citation: J Clin Microbiol. 2009 Apr;47(4):1274-5
references.pmid: 19171685
references.citation: Yonsei Med J. 2010 Jan;51(1):104-10
references.pmid: 20046522
references.citation: Arch Dis Child. 2002 Jan;86(1):44-6
references.pmid: 11806883
references.citation: Proc Natl Acad Sci U S A. 2002 May 14;99(10):7039-44
references.pmid: 11983869
references.citation: Pediatrics. 2007 May;119(5):891-6
references.pmid: 17473088
references.citation: J Clin Microbiol. 2005 Sep;43(9):4823-5
references.pmid: 16145149
references.citation: Zhonghua Er Ke Za Zhi. 2004 Sep;42(9):663-7
references.pmid: 15482666
references.citation: J Clin Microbiol. 2002 May;40(5):1575-80
references.pmid: 11980924
references.citation: Acta Paediatr. 1997 Oct;86(10):1097-9
references.pmid: 9350892
references.citation: J Perinatol. 2003 Mar;23(2):117-22
references.pmid: 12673260
references.citation: Pediatr Infect Dis J. 1996 Jul;15(7):615-20
references.pmid: 8823857
references.citation: Clin Chim Acta. 2003 Nov;337(1-2):11-21
references.pmid: 14568176
references.citation: Nat Rev Microbiol. 2008 Jul;6(7):553-8
references.pmid: 18521073
references.citation: J Clin Microbiol. 2008 Aug;46(8):2613-9
references.pmid: 18550744
references.citation: Zhonghua Er Ke Za Zhi. 2007 Jun;45(6):446-9
references.pmid: 17880793
references.citation: J Microbiol Methods. 2007 Feb;68(2):296-302
references.pmid: 17046087
references.citation: JAMA. 2004 Nov 17;292(19):2357-65
references.pmid: 15547163
references.citation: J Med Microbiol. 2007 Feb;56(Pt 2):223-228
references.pmid: 17244804
references.citation: Clin Microbiol Rev. 2010 Jan;23(1):235-51
references.pmid: 20065332
references.citation: Medicine (Baltimore). 2008 Jul;87(4):234-249
references.pmid: 18626306
references.citation: J Clin Microbiol. 2007 Feb;45(2):299-302
references.pmid: 17122016
references.citation: Med Mycol. 2003 Oct;41(5):369-81
references.pmid: 14653513
references.citation: Lancet. 2010 Jan 16;375(9710):224-30
references.pmid: 20004964
references.citation: Arch Pediatr Adolesc Med. 2009 Jan;163(1):6-11
references.pmid: 19124696
references.citation: Clin Pediatr (Phila). 2009 Jul;48(6):641-7
references.pmid: 19407210
references.citation: J Clin Microbiol. 2010 Jan;48(1):258-67
references.pmid: 19923485
references.citation: J Clin Microbiol. 1998 May;36(5):1169-75
references.pmid: 9574670
references.citation: FEMS Microbiol Rev. 2000 Apr;24(2):193-219
references.pmid: 10717314
references.citation: Antimicrob Agents Chemother. 2008 Oct;52(10):3558-63
references.pmid: 18663022
references.citation: Int J Antimicrob Agents. 2008 Nov;32 Suppl 1:S51-9
references.pmid: 18718741
references.citation: Clin Infect Dis. 1999 Sep;29(3):475-86; quiz 487-8
references.pmid: 10530433