Yield of targeted PCR in probable early onset sepsis: a prospective cohort study in (near)-term neonates with negative blood cultures

Abstract

Abstract Background Discriminating non-infected from infected neonates 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 PCR for group B streptococcus (GBS) and E. coli on left-over blood-culture media from term neonates with a probable early onset sepsis (EOS). Methods Left-over blood culture material from neonates participating in the RAIN study (iv-oral antibiotic switch in probable bacterial infection (risk factors and/or clinical signs and elevated inflammatory parameters but negative blood culture) was stored after 5 days of incubation. We applied 2 targeted PCRs for GBS and E. coli, the main pathogens in EOS, and analysed the samples batch-wise in triplicate for each PCR. Results PCR was performed in triplicate on blood culture media from 284 neonates. In 23/284 neonates, PCR was positive (3 x Ct values < 37) for GBS or E. coli (1 GBS, 22 E. coli). Inflammatory parameters did not discriminate for positive PCR, neither risk factors for sepsis, such as maternal GBS status and prolonged rupture of membranes. However, 96% of neonates with positive PCR were born vaginally versus 74% in the PCR-negative group (p=0.02); and 96% versus 81% (p=0.08) of neonates had clinical symptoms. Conclusions Blood culture-negative ‘probable’ EOS in neonates is accompanied by ∼8% of positive PCR, suggesting low-grade bacteriaemia 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 neonates highly suspected of infection but in the absence of a positive blood culture.