A renal transplant recipient has been on suppressive valacyclovir for recurrent genital herpes. She now develops progressive vesicular lesions unresponsive to dose escalation. HSV isolated from the lesions shows a markedly reduced thymidine kinase activity. The most appropriate next drug is:

• A Famciclovir
• B Ganciclovir
• C Higher-dose acyclovir
• D Foscarnet ✓

Explanation

Acyclovir, valacyclovir and famciclovir all require initial phosphorylation by viral thymidine kinase to become active triphosphates. Thymidine kinase deficient mutants are cross resistant to all three guanine nucleoside analogues. Foscarnet inhibits viral DNA polymerase directly and does not need any viral kinase activation, so it remains effective against TK deficient HSV. Ganciclovir also depends on kinase-mediated phosphorylation.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.