A transplant recipient develops CMV retinitis caused by a strain resistant to ganciclovir due to mutations in the UL97 kinase gene. Which drug remains effective against this isolate?
- A Valganciclovir, because it bypasses UL97 through oral prodrug absorption
- B Cidofovir, because it is activated solely by host enzymes and therefore unaffected by any resistance mechanism
- C Foscarnet, because it directly inhibits viral DNA polymerase without requiring viral kinase activation ✓
- D Letermovir, because it acts on the terminase complex downstream of UL97
Correct answer: C. Foscarnet, because it directly inhibits viral DNA polymerase without requiring viral kinase activation
Explanation
Ganciclovir requires initial phosphorylation by the viral UL97 kinase; mutations in this gene confer resistance that foscarnet circumvents because it binds the pyrophosphate site of viral DNA polymerase directly and needs no kinase activation. This makes foscarnet the standard choice for ganciclovir-resistant CMV. Cidofovir is indeed activated by host kinases but can still be limited by polymerase mutations, and letermovir is approved for prophylaxis rather than treatment of established retinitis.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.