The management of acute meningitis: an update

Lumbar puncture

LP is the key investigation as it enables confirmation of meningitis and reveals the aetiology. In the UK, the median time from admission to LP is 17 hours despite national recommendations for an LP to be performed within 1 hour of arrival to hospital and preferably prior to antibiotics.³ The likelihood of detecting a pathogen decreases over time and, while getting an LP done within an hour is not always possible, it should be done as soon as is practically possible.^2,8 In patients with predominantly sepsis or a rapidly evolving rash, LP is not recommended (Box 1).¹

Cerebrospinal fluid cell count

Van de Beek and colleagues reported that >90% of adults with bacterial meningitis had a CSF leukocyte count >100 cells/μL.⁶ Absence of leukocytosis makes meningitis unlikely, but does not rule it out. A Danish study found an absence of leukocytosis in 2% of patients with bacterial meningitis, with a higher frequency in pneumococcal meningitis, a finding that was replicated in a Dutch study, which found immunocompromise was also a risk factor.^9,10

Cerebrospinal fluid leukocyte differential

A predominance of neutrophils in the CSF suggests bacterial meningitis while predominance of lymphocytes suggests viral meningitis. Important exceptions include a predominance of lymphocytes in bacterial meningitis if antibiotics have been given prior to LP and with certain bacteria (such as Listeria monocytogenes and in tuberculous meningitis).¹¹ A predominance of neutrophils can be seen in early viral meningitis as well, especially with enterovirus.¹²

CSF biochemistry

CSF protein, glucose and lactate give an indication as to the aetiology of meningitis but are not definitive (Table 1).¹ In a recent cohort study, a CSF:blood glucose ratio <0.6 detected all cases of bacterial meningitis but was not specific.⁵ A CSF protein of <0.6 g/L makes bacterial meningitis unlikely.¹³ CSF lactate has a high sensitivity and specificity in distinguishing between bacterial and viral meningitis if antibiotics have not been given beforehand, a cut off of 35 mg/dL has been suggested to have the best sensitivity for distinguishing between bacterial and viral meningitis.¹⁴

Clinical prediction models

A recent systematic review and validation of clinical prediction models found that none of the tested models had both sufficient sensitivity and specificity to be recommended for routine clinical use.¹⁵

CSF microscopy and culture

CSF microscopy with Gram stain is useful for rapid detection of bacteria. CSF culture is diagnostic in 70%–85% of cases prior to antibiotic exposure.¹¹ However, in a recent UK study, CSF culture was positive in only 23% of cases of bacterial meningitis when the median time to LP was several hours after antibiotic administration.² CSF sterilisation can occur within 2 hours and 4 hours of antibiotic administration for meningococci and pneumococci, respectively.⁸

CSF polymerase chain reaction

CSF polymerase chain reaction (PCR) can rapidly detect viruses and bacteria in the CSF with high specificity. It is the gold standard for detection of viruses and is increasingly relied upon in the diagnosis of bacterial meningitis, especially when antibiotics have been given prior to LP. Over 50% of meningococcal disease is diagnosed by PCR alone in the UK.¹⁶ Multiplex PCR, which can detect multiple pathogens at once, are increasingly being used with reasonable diagnostic accuracy reported.¹⁷

Whole genome sequencing techniques

Although not currently in routine clinical use, studies have shown that different sequencing methods on CSF identified unexpected pathogens not detected by conventional methods. However, they failed to detect some pathogens found by conventional microbiological testing.^4,18 Further work is needed to evaluate the clinical impact of such techniques.

Blood tests

Blood cultures should be taken in all cases of suspected meningitis prior to administration of antibiotics (Fig 1).¹ Blood meningococcal and pneumococcal PCR are also recommended and have been shown to substantially increase detection of meningococcal disease, and remain positive for several days after antibiotic initiation.^2,19

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Fig 1.

Recommended investigations in acute meningitis and meningococcal sepsis. CSF = cerebrospinal fluid; CRP = C-reactive protein; HSV = herpes simplex virus; LP = lumbar puncture; PCR = polymerase chain reaction; rRNA = ribosomal ribonucleic acid; VZV = varicella-zoster virus. Adapted with permission from McGill F, Heyderman RS, Michael BD et al. The UK Joint Specialist Societies Guideline on the diagnosis and management of acute meningitis and meningococcal sepsis in immunocompetent adults. J Infect 2016;72:405–38 under CC BY-NC-ND 4.0 licence.

Although some studies have shown procalcitonin has good sensitivity and specificity for differentiating bacterial from viral meningitis, it should be interpreted with the rest of the clinical picture not be the sole determinant.²⁰

Swabs

Throat, nasopharyngeal and stool swabs are useful for detecting enteroviruses if the CSF PCR is negative. Methicillin-resistant Staphylococcus aureus screening swabs should be taken. A bacterial throat swab should also be taken from cases with suspected meningococcal disease to provide information about the infecting strain in PCR-confirmed cases.¹

Steroids

A Cochrane review found that steroids led to a small reduction in mortality in pneumococcal meningitis and reduced hearing loss and neurological sequelae for all causes.²³ They concluded that current data supports their use in high-income settings in acute meningitis but not in low-income settings.²³

Current UK guidance recommends that intravenous dexamethasone 10 mg 6 hourly should be commenced on admission shortly before or simultaneously with antibiotics and up to 12 hours after for patients with suspected meningitis.¹ Compliance with this recommendation in the UK is poor, with only 20% of patients given steroids.³ If pneumococcal meningitis is confirmed, dexamethasone should be continued for 4 days.

Antibiotic choice

Consideration should be given to patient risk factors. In those with relative or overt immunocompromise (see details earlier), amoxicillin/ampicillin should be added to cover Listeria. A recent UK study showed that only 28% of patients aged >60 years and 31% of those immunocompromised received anti-listerial antibiotics.³ In those with a travel history to an area with a high prevalence of penicillin-resistant pneumococci, then vancomycin or rifampicin should be added.¹

Viral meningitis

There is no specific treatment for viral meningitis, but clinical trials are lacking. Treatment with aciclovir is of proven benefit in herpes encephalitis, therefore, if the patient has encephalitic features, aciclovir should be given. A prospective observational study in the UK showed that 43% of patients with HSV/VZV meningitis received ≥5 days of antivirals despite no evidence showing benefit.²

New treatments

The mortality associated with meningitis is still 10%–20%, much of this is due to associated inflammation. Current trials are aimed at reducing inflammation. An ongoing randomised trial is assessing whether the addition of daptomycin to standard treatment improves outcomes.²⁴ Daptomycin is primarily being used for its anti-inflammatory properties in this context rather than its antimicrobial ones.²⁵ Pre-clinical studies have shown that adjuvant treatment with C5 inhibitors dampen down complement-associated damage and improve outcomes in an experimental model of pneumococcal meningitis.²⁶