Drug May Work For Resistant CMV Infections in Transplant Recipients

DENVER—Cidofovir with or without adjunctive therapy may be an appropriate treatment option for ganciclovir-resistant cytomegalovirus (CMV) infections in solid organ transplant (SOT) recipients, according to study findings reported at the 53rd Interscience Conference on Antimicrobial Agents and Chemotherapy.

“There is no standard of care and there has been little evidence on which agent to use in solid organ transplantation,” said study investigator Katherine Perez, PharmD, an infectious diseases clinical specialist at Houston Methodist Hospital in Texas.

The study is the first to show the possible usefulness of cidofovir in treating ganciclovir-resistant infections among transplant recipients, and the findings could give clinicians some guidance on what to use, Dr. Perez said.

Dr. Perez and her colleagues conducted a single-center analysis of all SOT recipients from 2009 through 2012. Valganciclovir universal prophylaxis was standard for the center and 1,549 patients were included in the analysis.

The researchers identified CMV infection in 284 of the 1,549 patients (18.3%) and genotypic resistance testing was obtained on 56 of the 284 patients (19.7%). Resistance mutations were identified in 20 of the 284 patients (median age 60 years), including 16 with a single UL 97 mutation, one with a UL54 mutation, and three with both mutations. The 16 patients with a single UL97 mutation included seven kidney recipients, one kidney/pancreas recipient, three heart recipients and two liver recipients. All of the UL54 mutations were found in lung recipients.

Ganciclovir-resistant CMV infections developed in 16 of 20 seronegative SOT recipients of seropositive donors. Detection of these infections occurred at a median of nine months from transplantation.  Cidofovir was used to treat 14 of the 20 patients with ganciclovir-resistant CMV infections.

Thirteen of 14 patients treated with cidofovir achieved CMV clearance at a median time of 4.5 months; they had sustained undetectable viral loads for a median follow-up of 10 months (range one month to three years). One patient died while on therapy. Foscarnet was used to treat six of the 20 patients. Two patients died while on foscarnet, and two patients responded but relapsed once foscarnet was stopped. One of these patients maintained low level viremia until cidofovir was added to foscarnet, and one patient was still on foscarnet at the time of the analysis. No significant changes in renal function were found based on serum creatinine clearance throughout treatment with foscarnet and cidofovir.

“Cidofovir and foscarnet are both two extremely nephrotoxic medications and that is one of the big reasons people shy away from using them, especially for this type of infection, because there is no real clear dosing strategy for it,” Dr. Perez told Renal & Urology News. “We actually did not see any significant changes in renal function for these patients. There was a slight increase in overall serum creatinine within the first 30 to 60 days, but it normalized.”

CMV infection is among the most prevalent and serious infectious complications following SOT, ganciclovir is considered the mainstay treatment. It is now well established that that antiviral resistance in CMV is common and represents a significant therapeutic challenge, Dr. Perez said.

The study included too few patients treated with foscarnet to allow a direct comparison with cidofovir, she said.

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