Walzer P D, Kim C K, Foy J M, Linke M J, Cushion M T
Veterans Administration Medical Center, Cincinnati, Ohio.
Antimicrob Agents Chemother. 1988 Jan;32(1):96-103. doi: 10.1128/AAC.32.1.96.
Inhibitors of folic acid synthesis were compared alone and in different combinations in the therapy of pneumocystosis in immunosuppressed rats. Sulfonamides (sulfamethoxazole, sulfadiazine, and sulfadoxine) and sulfones (dapsone) used alone were very active against Pneumocystis carinii, as judged by histologic examination of the lungs and by organism quantitation. Improved efficacy could not be demonstrated by the addition of an inhibitor of dihydrofolate reductase to the regimen. Dihydrofolate reductase inhibitors (trimethoprim, diaveridine, and pyrimethamine) used alone were ineffective against P. carinii. All drugs were well tolerated except pyrimethamine, which caused bone marrow depression; folinic acid ameliorated this adverse reaction but did not interfere with P. carinii treatment. These data have potential clinical implications but need to be interpreted with caution and in light of other systems of P. carinii drug evaluation.
在免疫抑制大鼠肺孢子虫病治疗中，对叶酸合成抑制剂单独使用及不同组合使用的情况进行了比较。通过肺组织学检查和病原体定量判断，单独使用的磺胺类药物（磺胺甲恶唑、磺胺嘧啶和周效磺胺）和砜类药物（氨苯砜）对卡氏肺孢子虫活性很强。在治疗方案中添加二氢叶酸还原酶抑制剂并不能提高疗效。单独使用的二氢叶酸还原酶抑制剂（甲氧苄啶、二甲氧苄啶和乙胺嘧啶）对卡氏肺孢子虫无效。除乙胺嘧啶导致骨髓抑制外，所有药物耐受性良好；亚叶酸可改善这种不良反应，但不影响卡氏肺孢子虫的治疗。这些数据具有潜在临床意义，但需要谨慎解读，并结合卡氏肺孢子虫药物评估的其他体系。
