Fox B C, Sollinger H W, Belzer F O, Maki D G
Department of Medicine, University of Wisconsin Medical School, Madison.
Am J Med. 1990 Sep;89(3):255-74. doi: 10.1016/0002-9343(90)90337-d.
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.
One hundred thirty-two adult patients selected to undergo renal transplantation participated in a randomized, double-blind, placebo-controlled trial.
Patients randomized to receive TMP-SMZ experienced fewer hospital days with fever (3.3% versus 7.7%, p less than 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 less than 0.005) and following discharge from the hospital (0.08 versus 0.30 per 100 days, p less than 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 less than 0.005) and bloodstream (one versus nine, p less than 0.01) and infections caused by enteric gram-negative bacilli (four versus 46, p less than 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 less than 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 less than 0.001).
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.
确定长期使用甲氧苄啶-磺胺甲恶唑（TMP-SMZ）预防肾移植后细菌感染的疗效、TMP-SMZ在移植患者中的吸收情况、预防措施对微生物群的影响以及预防措施的成本效益。
132名择期进行肾移植的成年患者参与了一项随机、双盲、安慰剂对照试验。
随机接受TMP-SMZ治疗的患者发热住院天数较少（3.3%对7.7%，p<0.001），在拔除尿道导管后的移植住院期间细菌感染显著减少（每100天0.76次对1.88次，p<0.005），出院后也减少（每100天0.08次对0.30次，p<0.001）。在移植住院期间，每日剂量320/1600mg预防效果极佳，而每日160/800mg的血药浓度意外偏低，仅对预防拔除导管后的尿路感染有效。预防措施对预防尿路感染（24次对54次，p<0.005）、血流感染（1次对9次，p<0.01）以及由肠道革兰氏阴性杆菌（4次对46次，p<0.001）、肠球菌（6次对22次，p=0.006）或金黄色葡萄球菌（1次对9次，p=0.01）引起的感染最为有效。预防措施在移植后早期不能预防与尿道导管相关的尿路感染，但在拔除导管后，将尿路感染风险降低了三倍（p<0.001）。两组之间对TMP-SMZ耐药的革兰氏阴性杆菌定植无显著差异；矛盾的是，接受TMP-SMZ治疗的患者念珠菌定植的可能性较小，可能是因为治疗感染时接触抗生素较少。接受预防治疗的患者由TMP-SMZ耐药细菌或念珠菌引起的感染率并不更高；然而，与安慰剂组患者相比，他们的感染更可能由耐药细菌引起（62%对18%，p<0.001）。
TMP-SMZ预防措施耐受性良好，可显著降低肾移植后细菌感染的发生率，尤其是尿路感染和血流感染，可预防卡氏肺孢子虫肺炎，且具有成本效益。移植后早期TMP-SMZ吸收不足，需每日服用320/1600mg以获得最佳疗效。预防措施对微生物群几乎没有明显影响。
