Overtreatment and Delays in Antiviral Therapy for Suspected Herpesvirus CNS Infections

Abstract

Introduction: Herpesviruses are a common cause of CNS infections, including encephalitis and meningitis. Guidelines recommend empirical antiviral therapy when herpesvirus CNS infection is suspected, as early treatment significantly reduces mortality in encephalitis. This practice, however, often results in treatment of patients without herpesvirus CNS infection. Methods: We analyzed adults with suspected CNS infection enrolled in two prospective cohorts (2012–2025). All patients receiving antiviral therapy for suspected CNS infection were included. PCR-confirmed herpesvirus CNS infection was considered appropriate treatment, and all others were classified as overtreatment. We quantified overtreatment and undertreatment, and examined the clinical context of delayed therapy (in herpesvirus cases) and prolonged therapy (in non-herpesvirus cases). Results: Among 1,785 patients, 506 (28%) received antiviral therapy. Of these, 436 (86% of treated; 24% of total) did not have herpesvirus CNS infection, while 70 (14% of treated; 4% of total) had PCR-confirmed herpesvirus CNS infection. All patients with herpesvirus encephalitis received antiviral treatment. Delayed treatment (>1 day after presentation) occurred in 9/70 (17%) herpesvirus CNS infection cases, mostly due to concurrent or alternative diagnoses. Continued treatment (≥7 days) in non-herpesvirus cases occurred in 18/436 (4%), predominantly while awaiting repeat PCR results. Discussion: In order to ensure all herpesvirus encephalitis cases were treated, nearly one-quarter of patients with suspected CNS infection received antiviral therapy, exposing many to potential adverse effects. Nevertheless, delayed therapy remained common among herpesvirus CNS infections, highlighting the challenge of early identification.