Cytomegalovirus Infection Rate among Heart Transplant Patients in Relation to Anti-thymocyte Immunoglobulin Induction Therapy

Abstract

During a 2-year period, 49 patients underwent heart transplantation at Rigshospitalet, Copenhagen. Nine (18%) were females and the mean age for all patients was 44 years (range 14–56 years). Immunosuppressive therapy included cyclosporin, azathioprine and steroids in all patients. 43 patients received in addition short-term (approx. 4 days) induction treatment with antithymocyte immunoglobulin (ATG). 17 patients received ATG Fresenius^®, 2.5mg/kg/day or ATGAM^®, 12.5 mg/kg/day, whereas the remaining 26 patients received ATG Merieux^®, 2.5 mg/kg/day. Prophylactic antimicrobial chemotherapy included ceftriaxone, acyclovir (1 g daily), nystatin, and pyrimethamine in toxoplasmosis mismatch patients. Serological assays for cytomegalovirus (CMV), Epstein-Barr virus, varicella-zoster virus, herpes simplex virus, legionella and toxoplasmosis as well as CMV and bacterial culturing were carried out before transplantation, at regular intervals and when clinically indicated. Five patients developed septicaemia. Nine had pulmonary bacterial infections, including 2 cases of legionella pneumonia. Two had Clostridium difficile diarrhoea. Three patients had Pneumocystis carinii pneumonitis. 24 patients (49%) had evidence of CMV infection/reactivation. Seven out of 10 CMV mismatch (pos donor/neg recipient) patients and 3 out of 12 CMV match (pos donor/pos recipient) patients developed clinical CMV disease. The rate of CMV infection/reactivation was significantly higher among patients who had CMV-positive donors (p < 0.01) and among patients receiving ATG Merieux^®, induction treatment (p < 0.0001). Logistic regression analysis showed that both positive CMV donor status and ATG Merieux^® induction treatment were significant independent predictors of CMV infection. Six patients (12%) died. Two out of 4 infection related deaths could be ascribed to CMV disease.