Fungal infections more common in transplant recipients given the drug
TORONTO—Alemtuzumab decreases the likelihood of allograft rejection but it may increase the risk of severe infections following renal transplantation, data suggest.
Until now, little was known about the epidemiology of infection associated with alemtuzumab use in solid-organ transplant recipients. The agent is a humanized monoclonal antibody directed against CD52, a cell-surface antigen expressed on the B and T lymphocytes, monocytes, and NK cells.
David Andes, MD, and his colleagues retrospectively studied 1,436 solid organ transplant recipients, of whom 720 received one or two IV doses of alemtuzumab (Campath-1H, Berlex) and 716 did not. The two groups were matched by transplant type and length of follow-up. In both groups, 81% were kidney transplant patients.
The immunosuppression therapy for the unexposed group consisted of basiliximab (65 patients), daclizumab (25 patients), OKT3 (42 patients) and ATG (63 patients). All the subjects in both groups received prophylactic antibiotics. Maintenance immunosuppression consisted of prednisone, cyclosporine, tacrolimus, sirolimus or mycophenolate mofetil in both groups. Antifungal prophylaxis included clotrimazole troches or nystatin swish and swallow for three months.
Fluconazole antifungal prophylaxis was not used routinely. A 90-day course of acyclovir was used for cytomegalovirus (CMV) prophylaxis in the renal transplant recipients, and a 90-day course of valganciclovir was used in liver transplants.
Alemtuzumab was associated with an increased risk of fungal infections even after adjustment for other types of immunosuppression. The risk of infection with varicella zoster virus was not significantly increased with alemtuzumab after adjusting for prednisone, tacrolimus, sirolimus, and cyclosporine.
Alemtuzumab, mycophenolate, and tacrolimus each independently increased the risk for BK virus infection fourfold. Alemtuzumab was independently associated with a nearly twofold increased risk of severe CMV disease. These infections tended to occur more than three months after transplantation.
“There were more bacterial infections, although there were not enough of them to specify a species or a site of infection,” said Dr. Andes, assistant professor of medicine in the division of infectious diseases at the University of Wisconsin in Madison.
Study findings were presented here at the annual meeting of the Infectious Diseases Society of America.