Yield of Targeted Polymerase Chain Reaction in Probable Early-Onset Sepsis: A Prospective Cohort Study in Term and Near-Term Neonates With Negative Blood Culture Results.

Abstract

Background: Discriminating noninfected from infected neonatal cases remains challenging, and subsequently many neonates are treated with antibiotics in the first week of life. We aimed to study the additional value of a targeted polymerase chain reaction (PCR) for group B streptococcus (GBS) and Escherichia coli on leftover blood culture media from term and near-term neonates with probable early-onset sepsis (EOS).

Methods: Leftover blood culture material from neonates participating in the RAIN study was stored after 5 days of incubation. The RAIN study evaluated intravenous-oral antibiotic switch in probable bacterial infection, defined as risk factors and/or clinical signs and elevated inflammatory parameters but negative blood culture results. We applied 2 targeted PCRs for GBS and E coli, the main pathogens in EOS, and analyzed the samples batchwise in triplicate for each PCR.

Results: PCR was performed in triplicate on blood culture media from 284 neonates. In 23 neonates, the PCR result was positive (3 cycle threshold values <37) for GBS (n = 1) or E coli (n = 22). Inflammatory parameters did not discriminate for positive PCR result, nor did risk factors for sepsis, such as maternal GBS status and prolonged rupture of membranes. However, 96% of neonates with a positive PCR result were born vaginally vs 74% in the PCR-negative group (P = .05); furthermore, 96% vs 81% (P = .21) of neonates had clinical symptoms.

Conclusions: Blood culture-negative "probable" EOS in neonates is accompanied by an 8% rate of PCR positivity, suggesting low-grade bacteriemia after birth with yet unclear clinical consequences. Further research should focus on how PCR can contribute to more targeted antibiotic use of neonates, specifically in those highly suspected of infection but in the absence of a positive blood culture result.