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. Keywords diagnosis; FISH; microarray; molecular; neonate; PCR; sepsis Neonatal sepsis is a frequent life-threatening problem in neonatal intensive care units, particularly in very-low-birthweight infants (VLBW; infants with birthweight <1500 g) [1][2][3]. Early-onset sepsis (EOS; sepsis in infants <72 h old) occurs in 1.5-1.9% of VLBW infants, and late-onset sepsis (LOS; onset after 72 h of life) in approximately 20% [1]. Coagulasenegative staphylococci (CONS), Staphylococcus aureus and fungi are responsible for most neonatal infections [1]. Neonatal mortality in LOS is approximately 18% overall and 36% in Gram-negative sepsis. Sepsis also increases neonatal morbidities including patent ductus arteriosus, need for intravascular access, need for parenteral nutrition, bronchopulmonary † Author for correspondence: Tel.: +1 832 824 3206, Fax: +1 832 825 3204, mohanv@bcm.edu.For reprint orders, please contact reprints@expert-reviews.com Financial & competing interests disclosureFunding for color printing of the figures was provided by AdvanDx (MA, USA). Mohan Pammi Venkatesh is funded by CHRCDA grant (NIH K12 HD41648). James Versalovic is supported by R01 AT004326-01A1 NIH/NCCAM, R01 DK065075-01 NIH/NIDDK and 1UH2HG083990-01 NIH/NHGRI. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript. NIH Public Access Author ManuscriptExpert Rev Anti Infect Ther. Author manuscript; available in PMC 2011 July 1. . In a large cohort of 6093 extremely low birthweight infants (ELBW; birthweight ≤1000 g), infected infants had a significantly higher incidence of adverse developmental outc...

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