| Popis: |
Questions have been raised regarding the safety of trimethoprim-sulfamethoxazole (TMP-SMZ) in organ transplantation, particularly adverse interactions with azathioprine and cyclosporine. In a prospective randomized, double-blind, trial in 132 patients that encompassed 33,876 patient-days, long-term prophylaxis with TMP-SMZ was found to significantly reduce the incidence of bacterial infection after renal transplantation. Prophylaxis was very well tolerated; none of the 66 recipients of TMP-SMZ, who took the drug for an average of 8.9 months, was withdrawn from the study because of hypersensitivity or toxic side effects. Serial measurements of hematologic parameters and liver function tests after transplantation in the two groups showed no significant differences. Recipients of cadaveric transplants, who were all given cyclosporine, randomized to receive TMP-SMZ had serum creatinine levels approximately 15% higher than those in control patients receiving cyclosporine (p less than 0.01); comparison of renal function by 24-hour endogenous creatinine clearances and technetium 99m-labeled diethylenetriamine-penta-acetic acid glomerular filtration rates in 17 patients crossed over to the alternate treatment group for 7 weeks, however, shows that the observed differences are reversible and represent inhibition of tubular excretion of creatinine by TMP in the presence of cyclosporine. Prophylaxis with TMP-SMZ had no discernable effect on cyclosporine pharmacokinetics: recipients of TMP-SMZ had blood levels of cyclosporine similar to those in patients in the placebo group. Episodes of graft rejection occurred at a similar frequency in the two groups (placebo, 50; TMP-SMZ, 44). We conclude that long-term prophylaxis with TMP-SMZ does not produce discernable hematologic, renal, or hepatic toxicity in renal transplant recipients nor does it augment nephrotoxicity with cyclosporine or increase the risk of rejection. TMP-SMZ may be used safely and is highly cost-beneficial for prophylaxis of infection in renal transplantation. |
