The algorithm below shows how pre-test probability could be combined with various criteria to determine which patients require empiric acyclovir:
This algorithm isn't perfect, but at least it provides an evidence-based framework to approach this decision. It is based on the following considerations:
-A patient with average risk for HSV infection (~1.5% pre-test probability) and negative Reller Criteria has a risk of HSV infection of ~1/17,000. A patient with a low pre-test probability of HSV (~0.5%) and a negative Bouza Criteria has a risk of HSV infection of ~1/14,000. The risk of acyclovir-induced nephrotoxicity from a short course of treatment isn't exactly clear, but probably much higher (e.g. ~1/20; Yildiz 2013). Therefore, the risk/benefit ratio doesn't favor the use of acyclovir in these cases.
-HSV-PCR is generally available within a day, so failure to provide empiric treatment would delay therapy by less than a day. HSV encephalitis is generally a more indolent process than bacterial meningitis, so one day's delay in therapy probably wouldn’t be catastrophic.
-Acyclovir is nephrotoxic and lowers the seizure threshold. Therefore, universal application of empiric acyclovir to all encephalopathic patients while awaiting an HSV PCR would cause harm.
-Various decision tools are available in the literature to exclude HSV infection on the basis of CSF chemistries and immunologic status. Although this remains controversial, these tools have been validated and may provide a framework for determining which patients require empiric acyclovir.
-An algorithm incorporating pre-test probability and published decision tools is proposed:
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