Molecular Culture for the Diagnosis of Neonatal Sepsis

Summary

Rationale: Early diagnosis of sepsis in neonates is complicated as the signs and symptoms are nonspecific. Although blood culture is the gold standard for the diagnosis, false-negative results and long incubation period of 36-72 hours limits the use of blood culture to rule out sepsis at initial suspicion. Since delay in diagnosis may lead to progressive deterioration, antibiotics are often started empirically at initial sepsis suspicion, awaiting results of the blood culture. Consequently, uninfected infants are often unnecessarily exposed to empirical antibiotics. To reduce unnecessary treatment of non-infected infants, an early, sensitive and specific diagnostic tool would be helpful to guide clinicians faster when to discontinue antibiotics. Molecular Culture (MC) via IS-pro is a novel, advanced, molecular culture technique which is able to culture bacteria within 4 hours after blood sampling. MC might thus be a potential diagnostic tool to detect or rule out sepsis in infants quickly, however data on MC for diagnosis of sepsis in this population is limited.

Objective: The aim of this study is to evaluate whether MC is of additive predictive value for the diagnosis sepsis in this vulnerable group.

Study design: Prospective observational cohort study. Study population: All infants suspected for neonatal sepsis of both early and late onset will be eligible for study participation. They will be treated according to the standard local guidelines.

Intervention (if applicable): In case of a suspicion of sepsis at birth, blood will be collected for a conventional blood culture as part of standard care. Additionally, a blood sample will be collected from the umbilical cord for MC.

In case of a suspicion of sepsis not directly postpartum, an additional blood sample will be taken for MC analysis, directly following sampling for conventional culture, implying no extra phlebotomy.

Main study parameters/endpoints: The main study parameter is the discordance in positive and negative outcomes of MC compared to outcomes of conventional blood culture. As the diagnostic accuracy of the conventional blood culture (the current gold standard) is being questioned, the predictive value of MC versus conventional blood culture towards clinical sepsis will also be tested.

Conditions

• Neonatal Sepsis, Early-Onset
• Culture Positive Neonatal Sepsis
• Culture Negative Neonatal Sepsis
• Clinical Sepsis
• Microbial Disease
• Neonatal Infection
• Microbial Colonization
• Neonatal Sepsis, Late-Onset

Interventions

DIAGNOSTIC_TEST

Molecular Culture

PCR based technique that amplifies the interspace region in bacterial DNA, that is located between the genes coding for 16S and 23S ribosomal subunits. Primers are used for the majority of known pathogenic phyla, i.e. FAFV, Bacteroidetes, Firmicutes and Proteobacteria. The nucleotide length of the Interspace region is species specific for bacterial single species. Bacteria all have one or multiple alleles for this interspace region. The combination of the amount of alleles, as well as the nucleotide strand length, makes for a specific profile that is distinctive for the species. Available software is able to match this profile to a particular pathogen, enabling confirmation and identification of bacteria in samples within 5 hours in our experimental workflow.

Sponsors & Collaborators

• InBiome

  collaborator UNKNOWN

• Jip Groen

  lead OTHER

Principal Investigators

• Tim GJ de Meij, MD, PhD · Pediatric Gastro-enterologist

Eligibility

Max Age

90 Days

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-07-15

Primary Completion

2025-03-31

Completion

2025-08-31

Countries

• Netherlands

Study Locations