A renal transplant recipient on tacrolimus develops painful perianal ulcers. Swab PCR is positive for HSV-2, but the lesions fail to respond to 10 days of aciclovir 400 mg three times daily. The next appropriate step is:
- A Switch to foscarnet after confirming aciclovir resistance by viral thymidine kinase (TK) gene sequencing or phenotypic susceptibility testing ✓
- B Increase aciclovir dose to 800 mg five times daily
- C Add valaciclovir 1 g three times daily to current aciclovir
- D Switch to ganciclovir intravenously
Explanation
Aciclovir resistance in HSV is most common in immunocompromised patients (transplant recipients, HIV/AIDS) and is primarily caused by mutations in the viral thymidine kinase (TK) gene, which is required to phosphorylate (activate) aciclovir. Confirmation requires TK gene sequencing or phenotypic susceptibility testing. Foscarnet (a pyrophosphate analogue that directly inhibits viral DNA polymerase without requiring TK activation) is the drug of choice for aciclovir-resistant HSV. Cidofovir is an alternative. Adding valaciclovir (a prodrug of aciclovir) will not overcome TK-mediated resistance.
Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.
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Written and medically reviewed by the StethoPrep medical team.