Restrepo B I, Ahrens J, Graybill J R
Veterans Administration Hospital, San Antonio, Texas.
Antimicrob Agents Chemother. 1989 Aug;33(8):1242-6. doi: 10.1128/AAC.33.8.1242.
Cryptococcal meningitis is increasing in frequency, in large part because of the advent of acquired immune deficiency syndrome. Using the murine cryptococcosis model, a new oral triazole, SCH39304, has been compared with two drugs in clinical use, fluconazole and amphotericin B. BALB/c mice (nu/nu and nu/+) were challenged intracerebrally or intranasally. Oral treatment was given daily with SCH39304 at doses of 1 to 60 mg/kg of body weight or fluconazole at doses of 1 or 5 mg/kg of body weight. Amphotericin B was given intraperitoneally three times weekly, at doses of 3 or 6 mg/kg. After intracerebral challenge, SCH39304 prolonged survival in doses as low as 1 mg/kg, a dose at which fluconazole was ineffective. At equal doses, SCH39304 consistently increased survival more than did fluconazole but not longer than did amphotericin B. SCH39304 significantly lowered colony counts in brains more than did fluconazole but no more than did amphotericin B. SCH39304 was also superior to fluconazole after intranasal challenge at equal doses. SCH39304 appears to be superior to fluconazole in mice when the drugs are given at equal doses. Clinical trials are warranted.
隐球菌性脑膜炎的发病率正在上升，很大程度上是由于获得性免疫缺陷综合征的出现。利用小鼠隐球菌病模型，一种新型口服三唑类药物SCH39304已与两种临床使用的药物氟康唑和两性霉素B进行了比较。对BALB/c小鼠（裸鼠和非裸鼠）进行脑内或鼻内感染。每日口服给予SCH39304，剂量为1至60mg/kg体重，或氟康唑，剂量为1或5mg/kg体重。两性霉素B每周腹腔注射3次，剂量为3或6mg/kg。脑内感染后，SCH39304在低至1mg/kg的剂量下即可延长生存期，而该剂量的氟康唑无效。在同等剂量下，SCH39304始终比氟康唑更能延长生存期，但不比两性霉素B更长。SCH39304比氟康唑更能显著降低脑内的菌落计数，但不比两性霉素B更多。在同等剂量鼻内感染后，SCH39304也优于氟康唑。当给予同等剂量的药物时，SCH39304在小鼠中似乎优于氟康唑。有必要进行临床试验。
