Improved Diagnostics in Bacterial Neonatal Meningitis Using a Next-Generation Sequencing Platform

Infectious Diseases and Therapy, vol. 12, pp. 1921–1933

Abstract

INTRODUCTION: Bacterial meningitis in infants is an infrequent but life-threatening condition. Empiric therapy should begin as soon as meningitis is thought likely. Consequently, the causative microorganisms may not always be detected using culturing techniques, as cerebrospinal fluid (CSF) cultures are influenced by antibiotics. Nucleic acid amplification tests, such as polymerase chain reaction (PCR) (multiplex panels), may overcome this limitation but require a priori knowledge of the likely pathogen present within the sample. With this in mind, we investigated to what extent a culture-free, broad-range 16S rRNA gene next-generation sequencing (NGS) platform (MYcrobiota) could add to the microbiological diagnosis of meningitis. METHODS: Retrospective cohort study at level III neonatal intensive care unit. Included were all infants with suspected meningitis admitted between 10 November 2017 and 31 December 2020. A comparison was made of the bacterial pathogen detection rate between MYcrobiota and conventional bacterial culture. RESULTS: In a 3-year period, 37 CSF samples (diagnostic and follow-up) from 35 infants with proven or possible meningitis were available for MYcrobiota testing. MYcrobiota detected the presence of bacterial pathogens in 11 samples (30%), in contrast with the conventional CSF culture, which detected bacteria in 2 of 36 samples (5.6%). CONCLUSION: Addition of 16S rRNA sequencing to conventional culturing greatly improved the identification of the aetiology of bacterial meningitis compared to culturing of CSF samples alone.

Authors 8

1. Alieke van der Hoeven corresponding Aachen Department of Medical Microbiology

   Leiden University Medical Center

   Affiliation as printed

   Department of Medical Microbiology, Leiden University Medical Center, Postzone E4-P, Postbus 9600, 2300 RC, Leiden, The Netherlands. A.vanderHoeven@LUMC.nl

   Department of Medical Microbiology, Leiden University Medical Center, Postzone E4-P, Postbus 9600, 2300 RC, Leiden, The Netherlands

2. Martha T. van der Beek corresponding Aachen Department of Medical Microbiology

   Leiden University Medical Center

   Affiliation as printed

   Department of Medical Microbiology, Leiden University Medical Center, Postzone E4-P, Postbus 9600, 2300 RC, Leiden, The Netherlands

3. Vincent Bekker Aachen Division of Neonatology Department of Paediatrics, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Division of Neonatology, Department of Paediatrics, Leiden University Medical Center, Leiden, The Netherlands

4. Erin Meijers Aachen Department of Medical Microbiology

   Leiden University Medical Center

   Affiliation as printed

   Department of Medical Microbiology, Leiden University Medical Center, Postzone E4-P, Postbus 9600, 2300 RC, Leiden, The Netherlands

5. Marco J. R. Ivens Aachen Department of Medical Microbiology

   Leiden University Medical Center

   Affiliation as printed

   Department of Medical Microbiology, Leiden University Medical Center, Postzone E4-P, Postbus 9600, 2300 RC, Leiden, The Netherlands

6. Els Wessels Aachen Department of Medical Microbiology

   Leiden University Medical Center

   Affiliation as printed

   Department of Medical Microbiology, Leiden University Medical Center, Postzone E4-P, Postbus 9600, 2300 RC, Leiden, The Netherlands

7. Aloys C.M. Kroes Aachen Department of Medical Microbiology

   Leiden University Medical Center

   Affiliation as printed

   Department of Medical Microbiology, Leiden University Medical Center, Postzone E4-P, Postbus 9600, 2300 RC, Leiden, The Netherlands

8. Stefan A. Boers corresponding Aachen Department of Medical Microbiology

   Leiden University Medical Center

   Affiliation as printed

   Department of Medical Microbiology, Leiden University Medical Center, Postzone E4-P, Postbus 9600, 2300 RC, Leiden, The Netherlands. S.A.Boers@LUMC.nl

   Department of Medical Microbiology, Leiden University Medical Center, Postzone E4-P, Postbus 9600, 2300 RC, Leiden, The Netherlands