J is a 45 year-old with history of living donor kidney transplant 9 months prior presents with progressive wasting and diarrhea despite 3 weeks of valganciclovir therapy for CMV syndrome. Repeat CMV quant from blood has increased from 7,000 to 19,000. J feels ill and is unable to keep up with fluid intake prompting admission to hospital. The allograft is functioning well with creatinine in normal range at baseline and current labs consistent only with mild dehydration. A resistance panel returns showing a UL97 & UL54 Resistance mutation to ganciclovir.
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Correct Answer: Foscarnet
This demonstrates a case of resistant CMV which has higher morbidity and mortality and requires appropriate therapy, which in this case empiric foscarnet is the best answer (or at least has the most data). This case demonstrates clinical resistance with increasing viral load and worsening clinical symptoms despite 3 weeks of oral valganciclovir. Remember that the viral load may lag behind clinical response, and often takes weeks to plateau and show improvement. However this case demonstrates persistent rise at 3 weeks and more worrisome, progressive symptoms prompting hospitalization. Additionally phenotypic resistance is documented with the UL97 (most common) and UL54 mutations. Foscarnet is the favored therapy with high level ganciclovir resistance as described this case.
Distractor answer choices
- Given the high level of resistance and switch to IV ganciclovir is unlikely to be sufficient.
- The UL54 mutation may confer resistance to cidofovir and/or foscarnet, but it is more strongly linked to cidofovir resistance and thus foscarnet is preferred as above
- Letermivir doesn’t have sufficient data in treatment of active disease within solid organ transplant to date, and in-vitro studies suggest a low threshold to resistance prompting concern for use with high disease burden described
- Acyclovir does not have activity to treat CMV.
HISTORICAL NOTE: This question was written prior to FDA approval of Maribavir for refractory CMV infections in transplant recipients. Hence, maribavir is not discussed in this question answer. Here is a link to an article that likely could spark further discussion: https://doi.org/10.1093/cid/ciab988
Links:
https://pubmed.ncbi.nlm.nih.gov/33115722/
Our friends at Febrile have put out 2 great podcast episodes about CMV (The Troll of Transplant). Check them out here!
- https://febrilepodcast.com/33-troll-transplant-1/
- https://febrilepodcast.com/episode-35-troll-of-transplantation-part-2/
Author: Jeremey Walker at UAB Edited by Todd McCarty
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This question was uploaded on 3/29/22