What is the role of oral Acyclovir (antiviral medication) in the treatment of aseptic meningitis?

Oral Acyclovir in Aseptic Meningitis

Oral acyclovir is not recommended for the treatment of aseptic meningitis as there is no evidence supporting its efficacy, and treatment should be primarily supportive with analgesia and fluids as needed. 1

Viral Meningitis Treatment Approach

• Aseptic meningitis is most commonly caused by viruses, with no proven benefit from antiviral treatments for most cases 1
• Despite some clinicians using acyclovir or valaciclovir for herpes meningitis (HSV or VZV), current guidelines explicitly state there is no evidence supporting this practice 1
• The potential risks of drug side effects and unnecessarily prolonged hospitalization outweigh the theoretical benefits given the lack of efficacy evidence 1
• Treatment should focus on supportive care with analgesia and fluids as necessary 1
• If antibiotics were started empirically, they should be discontinued once a viral diagnosis is confirmed, with priority given to expediting hospital discharge 1

Important Distinction: Meningitis vs. Encephalitis

• Intravenous acyclovir (10 mg/kg three times daily) is indicated for viral encephalitis, particularly when HSV or VZV is suspected, but not for uncomplicated aseptic meningitis 1
• If there are any signs of encephalitis (changes in personality, behavior, cognition, or altered consciousness), intravenous acyclovir should be initiated and the British Infection Association/Association of British Neurologists guidelines for encephalitis management should be followed 1
• The distinction between meningitis (inflammation of the meninges) and encephalitis (inflammation of the brain parenchyma) is critical for treatment decisions 1

Special Case: Recurrent HSV-2 Meningitis (Mollaret's Syndrome)

• Recurrent lymphocytic meningitis (Mollaret's meningitis) is most commonly caused by HSV-2 1, 2
• Despite oral valaciclovir's effectiveness in reducing genital HSV-2 transmission and recurrences, a placebo-controlled trial showed it did not reduce recurrent HSV-2 meningitis 1, 3
• Surprisingly, patients who received valaciclovir in this trial tended to have a higher rate of relapse after stopping treatment, suggesting a possible rebound phenomenon 1, 3
• The ineffectiveness was hypothesized to be due to inadequate drug levels in the CSF 1

Evidence Quality and Considerations

• The most recent and highest quality evidence (UK Joint Specialist Societies guideline, 2016) explicitly recommends against oral acyclovir for aseptic meningitis 1
• Some older, smaller studies suggested possible benefits of acyclovir in HSV-2 meningitis 4, 5, but these are outweighed by the more recent randomized controlled trial showing no benefit and potential harm with valaciclovir 3
• The 2012 study by Aurelius et al. found that suppressive treatment with valaciclovir 0.5g twice daily did not prevent recurrent meningitis and showed a concerning higher frequency of meningitis after cessation of the drug 3

Common Pitfalls in Management

• Failing to distinguish between viral meningitis (where oral acyclovir is not indicated) and HSV encephalitis (where intravenous acyclovir is essential) 1
• Unnecessarily prolonging hospitalization and antibiotic/antiviral treatment after confirming viral meningitis 1
• Using oral antivirals for recurrent HSV-2 meningitis based on their effectiveness in genital herpes, despite evidence showing lack of efficacy in meningitis 1, 3
• Misdiagnosing drug-induced aseptic meningitis (such as from amoxicillin) as viral meningitis requiring antiviral treatment 6

In summary, while intravenous acyclovir has a clear role in the management of HSV encephalitis, current evidence does not support the use of oral acyclovir in the treatment of aseptic meningitis, including HSV-2 meningitis.