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

April 24, 2018

July 25, 2018

Alexander Zozula, Resident Physician (Stanford University Department of Emergency Medicine)

Christopher Stave, Stanford University Department of Emergency Medicine

In [adults 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 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

PubMed -- 506 results
EMBASE -- 643 results
Total -- 742 unique results

106 full text articles were reviewed after screening titles/abstracts from which 33 original articles and two systematic reviews were ultimately selected for inclusion. One of the 33 articles (Schwarz et al.) was initially screened out but ultimately included after reviewing the two systematic reviews and the full text of the article. 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 3.5mM (~31mg/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. With over 30 studies supporting its use over the past 40 years, it appears ready for routine use.

1. Abro et al.. CSF lactate level: a useful diagnostic tool to differentiate acute bacterial and viral meningitis.
2. Abro et al.. Cerebrospinal fluid analysis: acute bacterial versus viral meningitis
3. Berg et al.. Cerebrospinal fluid lactate in the diagnosis of meningitis. Diagnostic value compared to standard biochemical methods.
4. 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.
5. Brook et al.. Measurement of lactic acid in cerebrospinal fluid of patients with infections of the central nervous system.
6. Buch et al.. Cerebrospinal fluid lactate as a marker to differentiate between community-acquired acute bacterial meningitis and aseptic meningitis/encephalitis in adults: a Danish prospective observational cohort
7. Chen et al.. The clinical diagnostic significance of cerebrospinal fluid d-lactate for bacterial meningitis
8. Curtis et al.. Cerebrospinal fluid lactate and the diagnosis of meningitis.
9. D'Souza et al.. Lactic-acid concentration in cerebrospinal fluid and differential diagnosis of meningitis.
10. Ellis and Oei. Cerebrospinal fluid lactic acid: a valuable aid in the of diagnosis septic meningitis.
11. Ferguson and Tearle. Gas liquid chromatography in the rapid diagnosis of meningitis.
12. Gastrin et al.. Rapid diagnosis of meningitis with use of selected clinical data and gas-liquid chromatographic determination of lactate concentration in cerebrospinal fluid.
13. Genton and Berger. Cerebrospinal fluid lactate in 78 cases of adult meningitis.
14. Giulieri et al.. CSF lactate for accurate diagnosis of community-acquired bacterial meningitis
15. Gould et al.. The use of cerebrospinal fluid lactate determination in the diagnosis of meningitis.
16. Herold et al.. Lactic acid in cerebrospinal fluid: evaluation and application of an automated enzymatic assay.
17. Hurd et al.. Use of cerebrospinal fluid lactate levels in the diagnosis of bacterial meningitis.
18. Jordan et al.. CSF lactate in diseases of the CNS.
19. Kleine et al.. New and old diagnostic markers of meningitis in cerebrospinal fluid (CSF).
20. Komorowski et al.. Cerebrospinal fluid lactic acid in diagnosis of meningitis.
21. Komorowski et al.. Comparison of cerebrospinal fluid C-reactive protein and lactate for diagnosis of meningitis.
22. Lagi et al.. Proposal for a New Score-Based Approach To Improve Efficiency of Diagnostic Laboratory Workflow for Acute Bacterial Meningitis in Adults
23. Landaas and Von Der Lippe. Chemical analyses for early differential diagnosis between bacterial and viral meningitis.
24. Lannigan et al.. Evaluation of cerebrospinal fluid lactic acid levels as an aid in differential diagnosis of bacterial and viral meningitis in adults.
25. Lauwers. Lactic-acid concentration in cerebrospinal fluid and differential diagnosis of meningitis.
26. Lester et al.. Value of CSF lactate in the differential diagnosis between bacterial meningitis and other diseases with meningeal involvement.
27. 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.
28. Mandal et al.. How useful is cerebrospinal fluid lactate estimation in differential diagnosis of meningitis?
29. Patterson et al.. Handheld Point-of-Care Cerebrospinal Fluid Lactate Testing Predicts Bacterial Meningitis in Uganda
30. Ponka et al.. The differential diagnosis of bacterial and aseptic meningitis using cerebrospinal fluid laboratory tests.
31. Schwarz et al.. Serum procalcitonin levels in bacterial and abacterial meningitis.
32. Viallon et al.. Meningitis in adult patients with a negative direct cerebrospinal fluid examination: value of cytochemical markers for differential diagnosis
33. de Almeida et al.. Quantitation of cerebrospinal fluid lactic acid in infectious and non-infectious neurological diseases
34. Huy et al.. Cerebrospinal fluid lactate concentration to distinguish bacterial from aseptic meningitis: a systemic review and meta-analysis
35. Sakushima et al.. Diagnostic accuracy of cerebrospinal fluid lactate for differentiating bacterial meningitis from aseptic meningitis: A meta-analysis