How Do We Distinguish Between Viral and Bacterial Meningitis?

This article was originally published in Portuguese on Medscape .

Bacteria and viruses are the leading causes of community-acquired meningitis. Bacterial meningitis is associated with high morbidity and mortality, and prompt treatment with appropriate antibiotics is essential to optimize outcomes. Early diagnosis is therefore crucial for selecting patients who need antibiotics. On the other hand, the course of viral meningitis is generally benign, and there is usually no specific antimicrobial treatment required. Distinguishing between viral and bacterial causes of meningitis can be challenging; therefore, many patients receive empiric antibiotic treatment.

Etiology

The most common etiologic agents of community-acquired bacterial meningitis are shown in the following table.

Newborns	Streptococcus agalactiae, Escherichia coli, Listeria monocytogenes
age 2 and younger	Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae
age 3-49	S pneumoniae, N meningitidis
age 50+	S pneumoniae, N meningitidis, and L monocytogenes

Among the etiologic agents of viral meningitis, the non-polio enteroviruses (Echovirus 30, 11, 9, 6, 7, 18, 16, 71, 25; Coxsackie B2, A9, B1, B3, B4) are the most common, responsible for more than 85% of cases. Other viruses potentially responsible for meningitis include the herpes simplex virus (HSV), primarily type 2, and flavivirus (such as the Dengue virus).

Clinical Presentation

The clinical presentation of bacterial meningitis is more severe than that of viral meningitis. The classic clinical triad of bacterial meningitis consists of fever, neck stiffness, and altered mental status. Only 41% of cases present with these three symptoms, however. Other clinical characteristics include severe headaches, decreased level of consciousness, nausea, vomiting, seizures, focal neurologic signs, and skin rash.

Viral meningitis is usually not associated with a decreased level of consciousness or significant decline in overall health status. The most frequently reported symptoms are unusual headaches, fever, nausea, vomiting, sensitivity to light, and neck stiffness. Patients may also present with skin changes and lymphadenopathy, and, depending on etiology, genital ulcers.

Diagnosis

The diagnosis of bacterial meningitis is based on clinical symptoms, blood panels (blood count, inflammation markers, cultures), and CSF cultures. Gram staining and latex agglutination may lead to false-negative results, and cultures may take a few days to provide a definitive result. Therefore, empiric antibiotic treatment is often started until the etiology can be determined.

A spinal tap must always be performed, preferably after a scan is taken, to rule out the risk of herniation. After CSF samples have been collected, they must undergo complete analysis, including cytological, biochemical, and microbiological evaluation, using conventional and molecular testing methods, when available.

Cytological and biochemical analyses of CSF may be helpful, as findings may indicate a higher probability of either bacterial or viral etiology.

CSF samples collected from patients with acute bacterial meningitis present characteristic neutrophilic pleocytosis (cell count usually ranging from hundreds to a few thousand, with > 80% polymorphonuclear cells). In some cases of L monocytogenes meningitis (from 25% to 30%), a lymphocytic predominance may occur. Normally, glucose is low (CSF glucose-to-blood glucose ratio of ≤ 0.4 or < 40 mg/dL), protein is very high (> 200 mg/dL), and the CSF lactate level is high (≥ 31.53 mg/dL).

In viral meningitis, the white blood cell count is generally 10-300 cells/mm³. Although glucose levels are normal in most cases, they may be below normal limits in lymphocytic choriomeningitis virus (LCMV), HSV, mumps virus, and poliovirus meningitis. Protein levels tend to be slightly elevated, but they may still be within the reference range.

A recent study investigated which of the cytological or biochemical markers best correlate with the definite etiologic diagnosis. This study, in which CSF samples were collected and analyzed from 2013 to 2017, considered cases of bacterial or viral meningitis confirmed via microbiological evaluation or polymerase chain reaction (PCR). CSF lactate was the best single CSF parameter, and CSF lactate above 30 mg/dL virtually excludes the possibility of a viral etiology.

Etiologic Determination

Despite the major contribution of globally analyzing CSF and secondary parameters, particularly CSF lactate, the precise etiologic definition is of great importance in cases of acute meningitis. Such precise definition is not simple, as identification of the causative microorganism is often difficult. Moreover, there are limits to conventional microbiological methods. Bacterioscopy is poorly sensitive, and although bacterial cultures are more sensitive, they can delay diagnosis because of the time it takes for the bacteria to grow in culture media.

Targeted molecular detection methods are usually more sensitive than conventional microbiological methods. Panel-based molecular tests identify multiple pathogens in a single test. In 2015, the US Food and Drug Administration authorized the first commercial multiplex detection system for infectious causes of community‑acquired meningitis and encephalitis. This test, the BioFire FilmArray system, detects 14 bacterial, viral, and fungal pathogens in a turnaround time of about 1 hour, including S pneumoniae, N meningitidis, H influenzae, S agalactiae (i.e., group B Streptococcus), E coli (serotype K1), L monocytogenes, HSV-1, HSV-2, varicella-zoster virus (VZV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), human parechovirus (HPeV), and Cryptococcus neoformans/gattii.

A meta-analysis of eight precise diagnostic studies evaluating the BioFire FilmArray system showed a high sensitivity of 90% (95% CI, 86% - 93%) and specificity of 97% (95% CI, 94% - 99%). The FilmArray ME panel can halve the time to microbiological result, allowing for earlier discontinuation of antimicrobial agents and hospital discharge in cases of viral meningitis.

Conclusion

Acute community-acquired meningitis is usually the result of viral or bacterial infections. Given the low specificity of clinical symptoms and, very often, of the general laboratory panel findings, many patients are empirically treated with antibiotics. High-sensitivity and specificity molecular techniques allow for rapid identification of the bacterial etiology (which requires antibiotic therapy) or the viral etiology of meningitis. The latter can be managed only with symptom-specific medications and does not usually require extended hospitalization. Therefore, these new techniques can improve the quality of care for these patients with viral meningitis.

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