Abstract

Nonculture infection tests of cerebrospinal fluid (CSF) samples using polymerase chain reaction and antigen or antibody assays are frequently ordered on lumbar puncture specimens concurrently with routine CSF cell counts, but the value of CSF infection testing in otherwise healthy children is unknown. To determine the value of nonculture CSF infection testing in immune-competent children with normal CSF cell counts. This cross-sectional study reviewed screening and diagnostic tests in the electronic medical record system of a large academic tertiary care children's hospital. Records of children aged 0.5 to 18.9 years (n = 4083) who underwent lumbar puncture (n = 4811 procedures) in an inpatient or outpatient facility of Children's Hospital of Philadelphia between July 1, 2007, and December 31, 2016, were reviewed. Those with indwelling CSF shunts or catheters; those with active or past oncologic, immunologic, or rheumatologic conditions; or those taking immune-suppressing medications were excluded from analysis. This study was conducted from July 20, 2017, to March 13, 2019. Outcome variables included frequency of nonculture CSF infection testing and frequency of positive results in the entire cohort, and among those with normal cell counts. Normal cell counts were defined as CSF white blood cell counts lower than 5 cells/μL and CSF red blood cell counts lower than 500 cells/μL. In total, 4811 lumbar puncture procedures were performed on 4083 unique children, with a median (range) age of 7.4 (0.5-18.9) years, 2537 boys (52.7%), and 3331 (69.2%) with normal CSF cell counts. At least 1 nonculture CSF infection test was performed on 1270 lumbar puncture specimens with normal cell counts (38.1%; 95% CI, 36%-40%), and more tests were performed in the summer months. Only 18 (1.4%; 95% CI, 0.9%-2.2%) of 1270 lumbar puncture specimens with normal cell counts had at least 1 nonculture infection test with a positive result; 2 of these 18 children required clinical intervention for their positive results, but each also had other clear clinical signs of infection. Nonculture CSF infection testing appeared to be common in immune-competent children with normal CSF cell counts, but positive results were uncommon and were not independently associated with clinical care; delaying the decision to send nonculture infection tests until CSF cell counts are available could reduce unnecessary diagnostic testing and medical costs, which may improve value-based care.

Highlights

  • Acute central nervous system (CNS) infections, such as meningitis and encephalitis, require prompt recognition of treatable etiologies to reduce potentially significant morbidity and mortality

  • At least 1 nonculture cerebrospinal fluid (CSF) infection test was performed on 1270 lumbar puncture specimens with normal cell counts (38.1%; 95% CI, 36%-40%), and more tests were performed in the summer months

  • Nonculture CSF infection testing appeared to be common in immune-competent children with normal CSF cell counts, but positive results were uncommon and were not independently associated with clinical care; delaying the decision to send nonculture infection tests until CSF cell counts are available could reduce unnecessary diagnostic testing and medical costs, which may improve value-based care

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Summary

Introduction

Acute central nervous system (CNS) infections, such as meningitis and encephalitis, require prompt recognition of treatable etiologies (eg, bacterial pathogens, herpes simplex virus [HSV]) to reduce potentially significant morbidity and mortality. Infections of the CNS are typically identified with lumbar puncture and evaluation of cerebrospinal fluid (CSF) cell counts, protein, glucose, Gram stain, bacterial culture, and nonculture infection tests. Introduction of peripheral blood into otherwise sterile CSF may result in the potential contamination of a bloodstream pathogen, and it makes the CSF WBC difficult to clinically interpret because an elevated count may reflect a true pleocytosis and/or peripheral blood WBCs. Polymerase chain reaction (PCR) of CSF and antigen or antibody assays are used to identify specific pathogens in suspected CNS infection; their overall diagnostic yield is variable. The positive and negative predictive values, as well as the clinical advantages of these tests in populations with a low pretest probability for CNS infection (such as immune-competent children with normal CSF cell counts), are unknown

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