Departamento de Microbiología, Facultad de Medicina, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico.
J Antimicrob Chemother. 2014 Apr;69(4):1075-8. doi: 10.1093/jac/dkt466. Epub 2013 Nov 19.
To study the effect of the initiation time of posaconazole treatment from 1 to 3 days after systemic infection by Trichosporon asahii in mice.
BALB/c mice, 4-5 weeks old, were intravenously infected with 1 × 10(7) cfu/mouse of T. asahii. The onset of treatment varied from 1 to 3 days after infection. Orally administered posaconazole at 0.5, 1, 2, 5 or 10 mg/kg body weight/day was compared with orally administered fluconazole (at 10 mg/kg/day) and intraperitoneally administered amphotericin B (at 1 mg/kg) on alternating days. Livers, kidneys and spleens of mice that died or survived to day 25 were removed to determine fungal tissue burdens.
When therapy began 1 day after challenge, posaconazole at ≥ 1 mg/kg significantly prolonged survival of mice compared with that of the control group and considerably reduced the fungal tissue burden over the control group. On the other hand, when treatment was started 3 days after infection, regimens of 5 and 10 mg/kg posaconazole significantly prolonged mice survival over that of the control group and appreciably diminished the fungal load compared with untreated mice. In this model, as the severity of trichosporonosis increased, higher doses of posaconazole were required to achieve equivalent activity levels. Fluconazole and amphotericin B were ineffective in preventing mice death and in significantly reducing fungal tissue burden. Posaconazole displayed potent in vivo activity against the strain tested.
Posaconazole may be a suitable option in the treatment of disseminated T. asahii infection.
研究泊沙康唑在系统性感染新生隐球菌后 1 至 3 天开始治疗的效果。
4-5 周龄 BALB/c 小鼠经静脉内感染 1×10(7)cfu/只新生隐球菌。治疗开始时间从感染后 1 天至 3 天不等。每天以 0.5、1、2、5 或 10mg/kg 体重的剂量口服泊沙康唑，与每天口服氟康唑（10mg/kg）和隔天腹腔内注射两性霉素 B（1mg/kg）进行比较。对死亡或存活至第 25 天的小鼠的肝脏、肾脏和脾脏进行取样，以确定真菌组织负荷。
当在挑战后 1 天开始治疗时，泊沙康唑≥1mg/kg 与对照组相比显著延长了小鼠的存活时间，并显著降低了真菌组织负荷。另一方面，当在感染后 3 天开始治疗时，5 和 10mg/kg 泊沙康唑方案显著延长了小鼠的存活时间，与未治疗的小鼠相比，真菌负荷明显降低。在该模型中，随着新生隐球菌病的严重程度增加，需要更高剂量的泊沙康唑才能达到等效的活性水平。氟康唑和两性霉素 B 不能预防小鼠死亡和显著降低真菌组织负荷。泊沙康唑对所测试的菌株显示出强大的体内活性。
泊沙康唑可能是治疗播散性新生隐球菌感染的一种合适选择。
