Drug-resistant CMV Infection

CMV (cytomegalovirus) infection is quite common in the transplant population, and fortuantely the development and utilization of valganciclovir (Valcyte), an oral prodrug of ganciclovir, as a prophylactic agent has dramatically cut down on the number of CMV infections in the transplant population.

However, CMV infections certainly can and do occur; it is important to know the donor & recipient CMV status (not surprisingly; a CMV-negative donor transplanted to a CMV-negative recipient is the lowest risk; a CMV-positive donor transplanted to a CMV-negative recipient is the highest risk).

In addition, the spectre of drug-resistant CMV infection is a difficult-to-manage scenario. We have one patient on our service currently who provides a nice demonstration of the different agents that can be used in the management of CMV. She presented with fevers and rising CMV titers while being treated with Valcyte; subsequent culture documented a true ganciclovir-resistant CMV strain. She was subsequently treated with foscarnet, until acute allograft dysfunction from foscarnet-induced nephritis forced us to stop this medication. She was later started on a regimen of weekly iv cidofovir infusions along with oral leflunomide, a drug initially developed for the treatment of rheumatoid arthritis as an immunosuppressant but later found to have both anti-BK and anti-CMV activity. While her viral load fell nearly 10-fold on this regimen, she had severe ocular toxicity (blurred vision, uveitis, and eye pain) which was felt to likely be due to cidofovir. She is presently being managed with leflunomide and decreased immunosuppression, and we will see how her CMV titers respond.