A 22-year-old immunocompromised patient develops progressive painful perianal ulcers. Tzanck smear shows multinucleated giant cells. PCR on the ulcer swab is positive for HSV-2. The drug of choice and its mechanism are:

• A Foscarnet; directly inhibits viral DNA polymerase without requiring phosphorylation
• B Acyclovir; phosphorylated by viral thymidine kinase then cellular kinases to acyclovir triphosphate inhibiting viral DNA polymerase ✓
• C Cidofovir; incorporated into viral DNA causing chain termination
• D Ganciclovir; phosphorylated by UL97 viral kinase in CMV

Explanation

Acyclovir is first-line for HSV infections; viral thymidine kinase (TK) phosphorylates acyclovir to acyclovir monophosphate (conferring >100-fold selectivity for virus-infected cells), and cellular kinases complete it to the triphosphate form, which competitively inhibits HSV DNA polymerase and acts as a chain terminator. Foscarnet is used for acyclovir-resistant HSV (TK-deficient mutants). Cidofovir is used for CMV retinitis and does not require viral TK. Ganciclovir is phosphorylated by CMV UL97.

Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.

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Written and medically reviewed by the StethoPrep medical team.