Neonatal Sepsis Diagnosis: ; PCR Commercial Technique and Blood Culture

NCT03884894 | Completed DMC

• 1 other identifier: IRCCSPSM/Eusepscreen/2015
• Study Type: observational
• Target: 69
• Locations: 1 country
• Sites: 1

Brief Summary

Although advances in neonatal care have improved survival and reduced complications in preterm infants, sepsis still contributes significantly to mortality and in Neonatal Intensive Care Units (NICUs), in particular for very-low-birth-weight (VLBW, \<1500 g) and extremely-low-birth-weight (ELBW, \<1000g). Based on the timing of the infection neonatal sepsis has been classified into early-onset sepsis (EOS) and late-onset sepsis (LOS), with differences in the mode of transmission and predominant organisms. EOS is defined as onset in the first 3 days of life generally due to vertical transmission of bacteria from mothers to infants during the intrapartum period. LOS occurs after 3 days of life and it is attributed to pathogens acquired postnatally (horizontal transmission). Considering generally neonatal sepsis in Europe, 90% of the responsible bacteria resulted to be: Streptococcus agalactiae, Escherichia coli, Klebsiella pneumoniae, e Listeria monocytogenes. The diagnosis is difficult because clinical signs, particularly early in the course of disease, are subtle and nonspecific, and laboratory tests and blood culture are not always reliable. Moreover. blood culture (considered the 'gold standard) takes 48-72 hours for result. In fact the cultural method requires the presence of living and vital germs, depends on the volume of the sample - serious problem in neonatal population -, several hours are needed to process the sample, possibly resulting falsely negative in subjects undergoing concomitant antibiotic treatment or a false positive result can be found by contamination. The method based on molecular biology does not require living germs and, therefore, is not characterised by the sensitivity limitations. Such method can result to be extremely effective in patients receiving antibiotic therapy. In the present study, when an infant has to undergone blood sample for bacteria culture to verify a possible sepsis, a residual blood (200µl) is processed in the same time using a kit based on molecular biology. This kit is designed to obtain the highest sensitivity and specificity in the determination of most invasive bacterial diseases (meningitis, sepsis, pneumonia, etc.) affecting full-term, preterm infants to determine any presence of bacterial DNA belonging to all serotypes of Klebsiella pneumoniae, Escherichia coli, Streptococcus agalactiae and Listeria monocytogenes. The target bacteria have been chosen on the basis of the current Italian epidemiological context, so as to include germs causing about 90% of the meningitis/sepsis cases among the neonatal population. The detection system can unmistakably identify the germ against which it is directed and without causing any cross-reaction with other germs or human DNA.. The results obtained with this method have demonstrated a 100% specificity (no false positive result) The sensitivity of this method compared with the cultural method has turned out to be twice as high. The aim of the present study is to compare the efficacy of the blood culture method and the kit for molecular detection of bacterial DNA (all serotypes of Klebsiella pneumoniae, Escherichia coli, Streptococcus agalactiae and Listeria monocytogenes) considering the relevant epidemiology of our NICU, in order to verify the relative frequency of sepsis (EOS and LOS) caused by the target bacteria on the whole frequency of the bacteria responsible of all the sepsis in our ward.

Conditions

Sepsis

Keywords

neonatal sepsis; Blood culture; molecular assay

Outcome Measures

Primary Outcomes (1)

• frequency of positive test

  to verify the frequency of positive test (neonatal sepsis, EOS or LOS) detected by the molecular assay compare to these of the blood culture

  1 week

Study Arms (1)

sepsis diagnosis by blood colture/molecular biology

fullterm/ preterm neonates hospitalized in NICU with suspect of sepsis

Diagnostic Test: molecular assay; Diagnostic Test: Blood culture

Interventions

molecular assay DIAGNOSTIC_TEST

performed with blood culture simultaneously

Also known as: "EuSepScreen lattanti" diagnostic kit

sepsis diagnosis by blood colture/molecular biology

Blood culture DIAGNOSTIC_TEST

performed with molecular assay simultaneously

sepsis diagnosis by blood colture/molecular biology

Eligibility Criteria

• Age: 1 Day - 30 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Neonates (full-term or pre-term) requiring to be sampled for suspected sepsis (EOS or LOS)

Sponsors & Collaborators

• Francesca Garofoli: lead

Study Sites (1)

Neonatal Unit, IRCCS Policlinico S. Matteo.

Pavia, PV, 27100, Italy

Location

Related Publications (2)

• • Istituto Superiore di Sanità. http//www.simi.iss.it/dati.htm • Shah BA, Neonatal sepsis: an old problem with new insights PadburyJF. Virulence 5:1, 163-171; January 1, 2014; © 2014 • Stoll BJ, Hansen NI, Sánchez PJ, Faix RG, Poindexter BB, Van Meurs KP, Bizzarro MJ, Goldberg RN, Frantz ID 3rd, Hale EC, et al.; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Early onset neonatal sepsis: the burden of group B Streptococcal and E. coli disease continues. Pediatrics 2011; 127:817-26. • Libster R, Edwards KM, Levent F, Edwards MS, Rench MA, Castagnini LA, Cooper T, Sparks RC, Baker CJ, Shah PE. Long-term outcomes of group B streptococcal meningitis. Pediatrics 2012; • Stoll BJ, Hansen N, Fanaroff AA, Wright LL, Carlo WA, Ehrenkranz RA, Lemons JA, Donovan EF, Stark AR, Tyson JE, et al. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network. Pediatrics 2002; 110:285-91; • Levy MM, Fink MP, Marshall JC et al. "2001 SCCM/ESICM/ACCP ATS/SIS International Sepsis Definitions Conference" Critical Care Medicine . 31 n 4 pp: 1250-1256, 2003. • Arnon S. Litmanovitz I. Diagnostic tests in neonatal sepsis. Curr Opinion Infectious Dis 2008; 21: 223-27. • Russell JA. Management of sepsis. N Engl J Med 2006;355:1699-713. • Overturf GD. Defining bacterial meningitis and other infections of the central nervous system. Pediatr Crit Care Med. 2005;6(3 Suppl):S14-8.

  BACKGROUND

• Mazzucchelli I, Garofoli F, Angelini M, Tinelli C, Tzialla C, Decembrino L. Rapid detection of bacteria in bloodstream infections using a molecular method: a pilot study with a neonatal diagnostic kit. Mol Biol Rep. 2020 Jan;47(1):363-368. doi: 10.1007/s11033-019-05138-2. Epub 2019 Oct 22.

  PMID: 31642041 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

blood samples

MeSH Terms

Conditions

Sepsis; Neonatal Sepsis

Interventions

Blood Culture

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Microbiological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Mauro Stronati, MD

  Fondazione IRCCS Policlinico S. Matteo, 27100 Pavia Italy

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Doctor

Study Record Dates

• First Submitted: March 20, 2019
• First Posted: March 21, 2019
• Study Start: January 1, 2015
• Primary Completion: January 1, 2016
• Study Completion: June 1, 2017
• Last Updated: July 24, 2024

Record last verified: 2024-07

Locations

IT (1)