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Phosphatidylcholine PC ae C44:6 in cerebrospinal fluid is a sensitive biomarker for bacterial meningitis

Authors
  • de Araujo, Leonardo Silva1, 2, 3
  • Pessler, Kevin1
  • Sühs, Kurt-Wolfram4, 5
  • Novoselova, Natalia6
  • Klawonn, Frank2
  • Kuhn, Maike1, 4
  • Kaever, Volkhard4
  • Müller-Vahl, Kirsten4
  • Trebst, Corinna4
  • Skripuletz, Thomas4
  • Stangel, Martin4, 7, 4, 5
  • Pessler, Frank1, 2, 5
  • 1 TWINCORE Centre for Experimental and Clinical Infection Research, Feodor-Lynen-Str. 7, Hannover, 30625, Germany , Hannover (Germany)
  • 2 Helmholtz Centre for Infection Research, Brunswick, Germany , Brunswick (Germany)
  • 3 Research Center Borstel-Leibniz Lung Center, Sülfeld, Germany , Sülfeld (Germany)
  • 4 Hannover Medical School, Hannover, Germany , Hannover (Germany)
  • 5 Centre for Individualised Infection Medicine, Hannover, Germany , Hannover (Germany)
  • 6 United Institute of Informatics Problems, Minsk, Belarus , Minsk (Belarus)
  • 7 Center for Systems Neuroscience, Hannover, Germany , Hannover (Germany)
Type
Published Article
Journal
Journal of Translational Medicine
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Jan 07, 2020
Volume
18
Issue
1
Identifiers
DOI: 10.1186/s12967-019-02179-w
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundThe timely diagnosis of bacterial meningitis is of utmost importance due to the need to institute antibiotic treatment as early as possible. Moreover, the differentiation from other causes of meningitis/encephalitis is critical because of differences in management such as the need for antiviral or immunosuppressive treatments. Considering our previously reported association between free membrane phospholipids in cerebrospinal fluid (CSF) and CNS involvement in neuroinfections we evaluated phosphatidylcholine PC ae C44:6, an integral constituent of cell membranes, as diagnostic biomarker for bacterial meningitis.MethodsWe used tandem mass spectrometry to measure concentrations of PC ae C44:6 in cell-free CSF samples (n = 221) from patients with acute bacterial meningitis, neuroborreliosis, viral meningitis/encephalitis (herpes simplex virus, varicella zoster virus, enteroviruses), autoimmune neuroinflammation (anti-NMDA-receptor autoimmune encephalitis, multiple sclerosis), facial nerve and segmental herpes zoster (shingles), and noninflammatory CNS disorders (Bell’s palsy, Tourette syndrome, normal pressure hydrocephalus).ResultsPC ae C44:6 concentrations were significantly higher in bacterial meningitis than in all other diagnostic groups, and were higher in patients with a classic bacterial meningitis pathogen (e.g. Streptococcus pneumoniae, Neisseria meningitidis, Staphylococcus aureus) than in those with less virulent or opportunistic pathogens as causative agents (P = 0.026). PC ae C44:6 concentrations were only moderately associated with CSF cell count (Spearman’s ρ = 0.45; P = 0.009), indicating that they do not merely reflect neuroinflammation. In receiver operating characteristic curve analysis, PC ae C44:6 equaled CSF cell count in the ability to distinguish bacterial meningitis from viral meningitis/encephalitis and autoimmune CNS disorders (AUC 0.93 both), but had higher sensitivity (91% vs. 41%) and negative predictive value (98% vs. 89%). A diagnostic algorithm comprising cell count, lactate and PC ae C44:6 had a sensitivity of 97% (specificity 87%) and negative predictive value of 99% (positive predictive value 61%) and correctly diagnosed three of four bacterial meningitis samples that were misclassified by cell count and lactate due to low values not suggestive of bacterial meningitis.ConclusionsIncreased CSF PC ae C44:6 concentrations in bacterial meningitis likely reflect ongoing CNS cell membrane stress or damage and have potential as additional, sensitive biomarker to diagnose bacterial meningitis in patients with less pronounced neuroinflammation.

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