Atkinson B A, Bocanegra R, Colombo A L, Graybill J R
Department of Medicine, University of Texas Health Science Center at San Antonio 78284-7881.
Antimicrob Agents Chemother. 1994 Jul;38(7):1604-7. doi: 10.1128/AAC.38.7.1604.
Torulopsis glabrata, an opportunist pathogen in immunosuppressed patients, is resistant to many antifungal agents, and there are no established treatment regimens for this organism. The mouse model was used to evaluate treatment with DO870, amphotericin B, fluconazole, and their combination. Mice were immunosuppressed with 5 mg of gold sodium thiomalate given intraperitoneally 1 day prior to intravenous infection with 10(8) T. glabrata cells. Treatment with a new antifungal triazole, DO870, at doses ranging from 1 to 50 mg/kg of body weight administered per os either daily or on alternate days; fluconazole at 100 mg/kg twice a day per os; or amphotericin B at 3 mg/kg/day intraperitoneally was begun 1 day after infection. Treatment for 5 days was followed by sacrifice 2 days later for determining CFU counts in spleen and kidney tissue. For a fluconazole-sensitive isolate (MIC of DO870, < 1.25 micrograms/ml), DO870 at 5 mg/kg/day significantly reduced counts in kidney and spleen tissue (P < 0.05), amphotericin B was modestly effective, and the combination of DO870 (25 mg/kg) and amphotericin B (3 mg/kg) was markedly more effective than either drug alone (P < 0.01). Three additional isolates were resistant in vitro to DO870 (MIC, 4 micrograms/ml). No reduction in CFU in kidney or spleen tissue was observed with DO870 when compared with counts in control tissue. DO870 is effective in vivo against at least some isolates of T. glabrata and when combined with amphotericin B can exert additive effects.
光滑念珠菌是免疫抑制患者的一种机会致病菌，对多种抗真菌药物耐药，且针对该菌尚无既定的治疗方案。采用小鼠模型评估DO870、两性霉素B、氟康唑及其联合用药的治疗效果。在静脉注射10⁸ 光滑念珠菌细胞前1天，给小鼠腹腔注射5mg硫代苹果酸钠金使其免疫抑制。感染后1天开始治疗，用一种新型抗真菌三唑类药物DO870，按1至50mg/kg体重的剂量每日或隔日口服给药；氟康唑按100mg/kg每日口服2次；或两性霉素B按3mg/kg/天腹腔注射。治疗5天后，2天后处死小鼠以测定脾脏和肾脏组织中的菌落形成单位（CFU）计数。对于一株对氟康唑敏感的菌株（DO870的最低抑菌浓度<1.25μg/ml），DO870按5mg/kg/天给药可显著降低肾脏和脾脏组织中的CFU计数（P<0.05），两性霉素B有一定疗效，DO870（25mg/kg）与两性霉素B（3mg/kg）联合使用比单独使用任何一种药物都更有效（P<0.01）。另外三株菌株在体外对DO870耐药（最低抑菌浓度为4μg/ml）。与对照组织中的计数相比，DO870处理后肾脏或脾脏组织中的CFU没有减少。DO870在体内对至少一些光滑念珠菌菌株有效，与两性霉素B联合使用可发挥相加作用。
