342 - Clinical Utility of a Next Generation Sequencing Test for Pathogen Detection in Pediatric Central Nervous System Infections

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Presenting Author(s)

Nanda Ramchandar

Pediatric Infectious Disease
Naval Medical Center San Diego
San Diego, California
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.

Co-Author(s)

JF

Jennifer Foley

Research Coordinator
Rady Children's Hopsital
San Diego, California
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
CE

Claudia Enriquez

Research Coordinator
Children's Hospital of Orange County
Orange, California
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
SO

Stephanie Osborne

Clinical Research Nurse Coordinator
Children's Hospital of Orange County
Orange, California
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Antonio C. Arrieta

Medical Director, Pediatric Infectious Disease
Children's Hospital of Orange County
Orange, CA
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
PS

Prithvi Sendi

Pediatric Critical Care Medicine
Nicklaus Children's Hospital
Miami, Florida
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
BT

Balagangadhar Totapally

Director, Division of Critical Care Medicine
Nicklaus Children's Hospital
Miami, Florida
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
DD

David Dimmock

Senior Medical Director Rady Children's Institute for Genomic Medicine
Rady Children's Institute for Genomic Medicine
San Diego, California
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
LF

Lauge Farnaes

Assistant Medical Director
Rady Children's Institute for Genomic Medicine
San Diego, California
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
DS

Daria Salyakina

Director
Nicklaus Children's Hospital
MIami, Florida
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
MJ

Michelin J. Janvier

Clinical Research Coordinator
Nicklaus Children's Hospital
Miami, Florida
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.

Background: Pediatric central nervous system (CNS) infections are potentially life-threatening and may incur significant morbidity. Identifying a pathogen is important, both in terms of guiding therapeutic management, but also in characterizing prognosis. However, standard care testing by culture, serology, and PCR is often unable to identify a pathogen. We examined use of next generation sequencing (NGS) of cerebrospinal fluid (CSF) in detecting an organism in children with CNS infections.

Methods: We prospectively enrolled children with CSF pleocytosis and suspected CNS infection admitted to 3 tertiary pediatric hospitals. After standard care testing had been performed, the remaining CSF was submitted for analysis by NGS.

Results: We enrolled 70 subjects over a 12-month recruitment period. A putative organism was isolated from CSF in 24 (34.3%) subjects by any diagnostic modality. NGS of the CSF samples identified a pathogen in 20 (28.6%) subjects. False positive results by NGS were identified in 2 patients. There were no cases in which NGS alone identified a pathogen. In 4 cases, a putative organism was recovered by standard care testing of the CSF, but not by CSF NGS. CSF culture recovered a putative organism in 12 cases (12.1%). A CSF PCR multiplex panel was utilized for 51 subjects. An organism was detected in 15 of these (29.4%). Using a reference composite of standard care testing, we determined the sensitivity and specificity of CSF NGS to be 83.3% (95% CI, 62.6-95.3%) and 91.3% (95% CI, 79.2-97.6%) respectively.

Conclusion: Sequencing of CSF has the potential to rapidly and comprehensively identify infection with a single test. Further studies are needed to determine the optimal use of NGS for diagnosis of CNS infections.