A PROSPECTIVE, RANDOMIZED, DOUBLE-BLIND-STUDY OF TRIMETHOPRIM-SULFAMETHOXAZOLE FOR PROPHYLAXIS OF INFECTION IN RENAL-TRANSPLANTATION - CLINICAL EFFICACY, ABSORPTION OF TRIMETHOPRIM-SULFAMETHOXAZOLE, EFFECTS ON THE MICROFLORA, AND THE COST-BENEFIT OF PROPHYLAXIS

purpose: To determine the efficacy of long-term prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMZ) for prevention of bacterial infection following renal transplantation, the absorption of TMP-SMZ in transplant patients, the effects of prophylaxis on the microflora, and the cost-benefit of prophylaxis. patients and methods: One hundred thirty-two adult patients selected to undergo renal transplantation participated in a randomized, double-blind, placebo-controlled trial. results: Patients randomized to receive TMP-SMZ experienced fewer hospital days with fever (3.3% versus 7.7%, p <0.001) and significantly fewer bacterial infections during the transplant hospitalization after removal of a urethral catheter (0.76 versus 1.88 per 100 days, p <0.005) and following discharge from the hospital (0.08 versus 0.30 per 100 days, p <0.001). During the transplant hospitalization, a daily dose of 320 1,600 mg was highly effective for prophylaxis whereas 160 800 mg daily gave unexpectedly low blood levels and was effective only for prevention of urinary tract infections after catheter removal. Prophylaxis was most effective in prevention of infections of the urinary tract (24 versus 54, p <0.005) and bloodstream (one versus nine, p <0.01) and infections caused by enteric gram-negative bacilli (four versus 46, p <0.001), enterococci (six versus 22, p = 0.006), or Staphylococcus aureus (one versus nine, p = 0.01). Prophylaxis did not prevent urinary tract infection associated with urethral catheters in the early posttransplant period, but after catheter removal, reduced the risk of urinary tract infection threefold (p <0.001). No significant differences in colonization by TMP-SMZ-resistant gram-negative bacilli were identified between the two groups; patients given TMP-SMZ were, paradoxically, less likely to become colonized by candida, probably because of less exposure to antibiotics for treatment of infection. Recipients of prophylaxis did not have a higher rate of infection caused by TMP-SMZ-resistant bacteria or Candida; however, their infections were more likely to be caused by resistant bacteria than infections in patients in the placebo group (62% versus 18%, p <0.001). conclusions: Prophylaxis with TMP-SMZ, which is well tolerated, significantly reduces the incidence of bacterial infection following renal transplantation, especially infection of the urinary tract and bloodstream, can provide protection against Pneumocystis carinii pneumonia, and is cost-beneficial. Subnormal absorption of TMP-SMZ in the early posttransplant period mandates 320 1,600 mg daily for optimal benefit. Prophylaxis has little discernible effect on the microflora. © 1990.