Dosing of intravenous ganciclovir for the prophylaxis and treatment of cytomegalovirus infection in solid organ transplant recipients

Background. The optimal regimen for the prevention and treatment of cytomeg alovirus (CMV) disease in solid organ transplant recipients remains to be d efined, particularly for patients with abnormal or changing renal function. Methods, A prospective trial was conducted in patients receiving i.v. ganci clovir using a standardized dosing:nomogram that corrects for renal functio n, Steady state peak (P) and trough (T) serum levels were determined by hig h-performance liquid chromatography and correlated with therapeutic outcome s and toxicities attributable to ganciclovir. Results, Over the study period, 44 individuals received ganciclovir prophyl axis (5 mg/kg/day) and 25 patients were treated (5 mg/kd q12 hr) for sympto matic CMV disease. Ganciclovir levels (mu g/ml+/-SD) achieved in prophylaxi s were P: 7.98+/-3.34, T: 3.03+/-2.63; and in treatment were P: 9.00+/-3.72 , T: 2.65+/-1.82. Despite corrections for renal dysfunction, undialyzed pat ients with serum creatinine >3.0 mg/dl had trough levels in excess of the p opulation mean (T: range 3-8 mu g/ml). Failure of prophylaxis (disease) or therapy (relapse) occurred in 14 patients; 8 of these were at risk for prim ary infection (donor CMV seropositive, recipient seronegative, P<0.01). Pat ients at greatest risk for relapse after treatment of CMV disease Were:live r transplant recipients, patients with ganciclovir-resistant viral isolates , and renal patients with six antigen MHC donor-recipient mismatches. Conclusions. This trial demonstrates the efficacy of a nomogram for gancicl ovir dosing during renal dysfunction; reduced doses can be used for prophyl axis for undialyzed patients with renal dysfunction (1.25 mg/kg/day for Cr greater than or equal to 3.0, 1.25 mg/kg QOD for Cr greater than or equal t o 5.0). Some groups of transplant recipients may require more intensive: an ti-CMV regimens.