Jim Kling

September 23, 2013

DENVER — Cidofovir might be superior to foscarnet in the treatment of ganciclovir-resistant cytomegalovirus in solid organ transplant recipients, new research has found.

"Until a few years ago, there weren't even a handful of case reports in the literature about using salvage therapies to treat ganciclovir-resistant cytomegalovirus in solid organ transplant recipients. But because we're doing so many more transplants now and using antivirals for prophylaxis more and more, we're starting to see this emerge," said Katherine Perez, PharmD, clinical specialist in infectious disease at Houston Methodist Hospital.

Dr. Perez presented the research here at the 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy.

She and her team had some bad experiences with foscarnet and searched for alternatives. They decided to try cidofovir, which is used to treat HIV patients with cytomegalovirus retinitis. "We had great success with it," said Dr. Perez.

Still, there are few data on clinical outcomes and tolerability in solid organ transplant recipients treated with these drugs.

"Right now, the literature really supports the use of foscarnet. The main reason is because that's what they've always done in stem cell transplantations. But those are different than solid organ transplants," Dr. Perez explained. "In addition, mutations can confer cross resistance to both cidofovir and ganciclovir, so some people don't want to take that chance. We were able to obtain genotypes and confirm that there wasn't resistance to cidofovir in our patients. We used it and were successful," she reported.

Foscarnet Standard of Care

The researchers conducted a single-center retrospective analysis of 1549 patients undergoing solid organ transplantation. All patients received valganciclovir prophylaxis.

Genotypic resistance testing was performed on 56 of the 284 patients (19.7%) who tested positive for cytomegalovirus infection.

Of the 20 patients with resistance mutations, 16 had a single UL97 mutation, 1 had a UL54 mutation, and 3 had both mutations. All UL54 mutations were in lung transplant recipients.

In 16 of the 20 cases of resistance mutations, the donor was seropositive and the recipient was seronegative. Resistance to ganciclovir was detected at a median of 9 months after transplantation.

Cidofovir is nice in that the dosing is convenient, but I personally would need to see further research.

In 14 of the 20 patients, including all with UL97 mutations, cidofovir was used to treat the infection. Thirteen achieved cytomegalovirus clearance at a median of 4.5 months, and remained free of detectable virus for a median follow-up of 10 months. One patient died while on cidofovir therapy.

The other 6 patients were treated with foscarnet. Two of these patients responded to the therapy but relapsed after discontinuation of foscarnet, 1 patient had low-level viremia until cidofovir was added to the regimen, and 1 patient remains on foscarnet. Two of these patients died.

The researchers observed no significant changes in renal function after treatment.

"This provides a totally new treatment option. I would consider it a first-line alternative to ganciclovir," Dr. Perez noted.

The work is encouraging, but some remain wary of cidofovir. "The study suggests that there might be another route outside of foscarnet. Cidofovir is nice in that the dosing is convenient, but I personally would need to see further research," said Daniel Kaul, MD, director of the transplant infectious disease service at the University of Michigan in Ann Arbor, who attended the session.

"In my experience, if you use cidofovir in solid organ transplant patients who have any hint of renal dysfunction — and many do, and they're almost universally on other nephrotoxic drugs — the renal failure rate is very high," he told Medscape Medical News.

"I'm not sure it necessarily changes what I personally would do, but there may be something different in the study population than in the patients I work with," Dr. Kaul added.

Dr. Perez and Dr. Kaul have disclosed no relevant financial relationships.

53rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC): Abstract T-343. Presented September 10, 2013.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.