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drug for an average of 8.9 months, was withdrawn from the study because of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.