Cerebrospinal fluid (CSF) lactate for distinguishing acute bacterial meningitis from acute viral meningitis in children

July 20, 2018

January 12, 2019

Alexander Zozula, EMS Fellow (University of Cincinnati Department of Emergency Medicine)

Christopher Stave, University of Cincinnati Department of Emergency Medicine

In [non-neonatal children undergoing lumbar punctures for possible meningitis] what are [the sensitivity and specificity of CSF lactate] for [diagnosing acute community-acquired bacterial meningitis]?

You are evaluating a pediatric patient in the emergency department in whom you are considering the diagnosis of acute community-acquired bacterial meningitis. You perform a lumbar puncture and when ordering CSF studies wonder if sending a CSF lactate would help distinguish acute bacterial meningitis (ABM) from acute viral meningitis (AVM).

PubMed
((("bacteria"[mesh] OR "bacterial infections"[mesh]) AND ("meningitis"[mesh:noexp])) OR "meningitis, bacterial"[mesh] OR (mening*[tw] AND (bacteria*[tw] OR escherichia[tw] OR haemophilus[tw] OR listeria[tw] OR meningococc*[tw] OR neisseria[tw] OR pneumococc*[tw] OR streptococc*[tw]))
AND (“cerebrospinal fluid”[mesh] OR “cerebrospinal fluid”[subheading] OR “cerebrospinal fluid”[tw] OR “CSF”[tw]) AND (“lactates”[mesh] OR lacta*[tw] OR lacti*[tw]))
AND english[lang]

EMBASE
(((‘bacterium’/exp OR ‘bacterial infection’/exp) AND ‘meningitis’/exp) OR (mening*:ab,ti,kw AND (bacteria*:ab,ti,kw OR ‘escherichia’:ab,ti,kw OR ‘haemophilus’:ab,ti,kw OR listeria:ab,ti,kw OR meningococc*:ab,ti,kw OR ‘neisseria’:ab,ti,kw OR pneumococc*:ab,ti,kw OR streptococc*:ab,ti,kw)))
AND ((‘cerebrospinal fluid'/exp OR ‘cerebrospinal fluid’:ab,ti,kw OR ‘CSF’:ab,ti,kw) AND (‘lactic acid'/exp OR lact*:ab,ti,kw))
AND [english]/lim

Searches were most recently run on December 19, 2018.

PubMed -- 518 results
EMBASE -- 658 results
Total -- 742 unique results

108 full text articles were reviewed after screening titles/abstracts from which 38 original articles and two systematic reviews were ultimately selected for inclusion. For completeness, the original articles included in the two systematic reviews are listed below as there appear to be several minor discrepancies in the data abstracted in the systematic reviews.

Distinguishing acute bacterial meningitis from acute viral meningitis can be challenging. While a strategy of treating all possible cases of ABM with broad spectrum antibiotics until CSF cultures result is commonly employed, this strategy may lead to antibiotic resistance and unnecessary hospitalization. A combination of CSF white blood cell count/differential, CSF glucose, and CSF protein is commonly used to distinguish ABM from AVM. Unfortunately these tests all suffer from suboptimal sensitivity and specificity. The ideal test would be maximally sensitive and specific, rapidly available, and cheap. Despite not being commonly used, CSF lactate has been widely studied and appears to satisfy all three domains. The median cutoff used in the included studies was 3.4mM (~30mg/dL), with the majority of studies using enzymatic assays. As with most CSF tests including the gold-standard culture, CSF lactate's utility is somewhat limited in patients pretreated with antibiotics. In such cases, a lower cutoff should be used to maintain sufficient sensitivity.

CSF lactate at a cutoff of 3.5mM appears to be both a sensitive and specific test for distinguishing acute bacterial meningitis from acute viral meningitis in non-neonatal children. With nearly 40 studies supporting its use over the past 40 years, it appears ready for routine use.

Level 1: Recent well-done systematic review was considered or a study of high quality is available

1. Briem et al.. Comparison between cerebrospinal fluid concentrations of glucose, total protein, chloride, lactate, and total amino acids for the differential diagnosis of patients with meningitis.
2. Brook et al.. Measurement of lactic acid in cerebrospinal fluid of patients with infections of the central nervous system.
3. Chen et al.. The clinical diagnostic significance of cerebrospinal fluid d-lactate for bacterial meningitis.
4. Curtis et al.. Cerebrospinal fluid lactate and the diagnosis of meningitis.
5. Ellis and Oei. Cerebrospinal fluid lactic acid: a valuable aid in the of diagnosis septic meningitis.
6. Ferguson and Tearle. Gas liquid chromatography in the rapid diagnosis of meningitis.
7. Gastrin et al.. Rapid diagnosis of meningitis with use of selected clinical data and gas-liquid chromatographic determination of lactate concentration in cerebrospinal fluid.
8. Hurd et al.. Use of cerebrospinal fluid lactate levels in the diagnosis of bacterial meningitis.
9. Jordan et al.. CSF lactate in diseases of the CNS.
10. Landaas and Von Der Lippe. Chemical analyses for early differential diagnosis between bacterial and viral meningitis.
11. Lester et al.. Value of CSF lactate in the differential diagnosis between bacterial meningitis and other diseases with meningeal involvement.
12. Lindquist et al.. Value of cerebrospinal fluid analysis in the differential diagnosis of meningitis: a study in 710 patients with suspected central nervous system infection.
13. Mandal et al.. How useful is cerebrospinal fluid lactate estimation in differential diagnosis of meningitis?
14. Ponka et al.. The differential diagnosis of bacterial and aseptic meningitis using cerebrospinal fluid laboratory tests.
15. de Almeida et al.. Quantitation of cerebrospinal fluid lactic acid in infectious and non-infectious neurological diseases.
16. Berg et al.. Cerebrospinal fluid lactate in the diagnosis of meningitis. Diagnostic value compared to standard biochemical methods.
17. Huy et al.. Cerebrospinal fluid lactate concentration to distinguish bacterial from aseptic meningitis: a systemic review and meta-analysis.
18. Sakushima et al.. Diagnostic accuracy of cerebrospinal fluid lactate for differentiating bacterial meningitis from aseptic meningitis: A meta-analysis.
19. Juarez Aragon et al.. Assessment of five laboratory tests for differential diagnosis in bacterial and viral meningoencephalitides.
20. Bland et al.. Cerebrospinal fluid lactic acid level and pH in meningitis. Aids in differential diagnosis.
21. Boon and Heng. Bacterial meningitis and cerebrospinal fluid lactate.
22. Cameron et al.. Cerebrospinal fluid lactate in meningitis and meningococcaemia.
23. Controni and Rodriguez. Diagnosis of pyogenic meningitis.
24. Controni et al.. Cerebrospinal fluid lactic acid levels in meningitis.
25. Donald and Malan. Cerebrospinal fluid lactate and lactate dehydrogenase activity in the rapid diagnosis of bacterial meningitis.
26. Dwivedi and Reddy. Diagnostic use of cerebrospinal fluid lactic acid levels in meningitis.
27. Eross et al.. Cerebrospinal fluid lactic acidosis in bacterial meningitis.
28. Knight et al.. Early (chemical) diagnosis of bacterial meningitis--cerebrospinal fluid glucose, lactate, and lactate dehydrogenase compared.
29. Low et al.. Cerebrospinal fluid lactate--its diagnostic value in septic meningitis.
30. Filho et al.. Cerebrospinal fluid lactate level as a diagnostic biomarker for bacterial meningitis in children.
31. Murata and Uemura. The diagnostic value of cerebrospinal fluid lactic acid levels in meningitis.
32. Nazir et al.. Cerebrospinal fluid lactate: a differential biomarker for bacterial and viral meningitis in children.
33. Nelson et al.. The diagnostic and predictive value of cerebrospinal fluid lactate in children with meningitis. Its relation to current diagnostic methods.
34. Rutledge et al.. Is the CSF lactate measurement useful in the management of children with suspected bacterial meningitis?
35. Ruuskanen et al.. CSF lactate in bacterial meningitis with minimal CSF abnormalities.
36. Pit et al.. Cerebrospinal fluid lactic acid concentration in bacterial meningitis.
37. Dashti et al.. Diagnostic value of lactate, procalcitonin, ferritin, serum-C-reactive protein, and other biomarkers in bacterial and viral meningitis.
38. Shaltout. Cerebrospinal fluid lactate is useful in differentiating viral from bacterial meningitis.
39. Uduman et al.. Haemophilus influenzae type b still remains a leading cause of meningitis among unvaccinated children--a prospective CSF analysis study.
40. Vanprapar et al.. Cerebrospinal fluid lactate level in childhood purulent meningitis.