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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Synergistic effect of clindamycin and atovaquone in acute murine toxoplasmosis.
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Synergistic effect of clindamycin and atovaquone in acute murine toxoplasmosis.

机译：克林霉素和阿托瓦醌在急性鼠弓形虫病中的协同作用。

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The effect of clindamycin (CLI) combined with autovaquone (ATO) was examined in a murine model of acute toxoplasmosis. Swiss Webster mice intraperitoneally infected with 10(2) or 10(4) tachyzoites of the RH strain of Toxoplasma gondii were perorally treated with either drug alone (for ATO, 5, 25, 50, or 100 mg/kg of body weight/day; for CLI, 25, 50, or 400 mg/kg/day) or both combined (for ATO plus CLI, respectively, 5 plus 25, 25 plus 25, 25 plus 50, 50 plus 50, or 100 plus 400 mg/kg/day) starting with day 1 for 14 days. Survival was monitored during 7 weeks. Residual infection was assessed by a bioassay of representative 4-week survivors and by parasite DNA detection by PCR for representative 7-week survivors. An effect of treatment was shown in all treatment groups compared to untreated control mice (P = 0.0000). Among mice infected with 10(2) parasites, ATO and CLI at any dose combination protected significantly more animals than ATO alone (P = 0.0000), but compared to CLI alone, given its good effect, the combined drugs were no more effective (P > 0.05). For mice infected with 10(4) parasites, the drugs combined at the lowest and highest doses (5 plus 25 and 100 plus 400 mg/kg/day) were, similarly, more effective than ATO alone (P = 0.035 and 0.000, respectively) but not than CLI alone (P > 0. 05). However, treatment with ATO plus CLI at 25 plus 25, 25 plus 50, and 50 plus 50 mg/kg/day protected 20, 33, and 78% of mice, respectively, compared to virtually no survivals among those treated with either drug alone (P < 0.0005), thus demonstrating a significant synergistic effect of ATO and CLI against T. gondii. Furthermore, the dose of ATO at a given dose of CLI was shown to be critical to the effect. Moreover, the absence of residual infection in some survivors shows the potential of this drug combination to eliminate the parasite.
机译：在急性弓形虫病的小鼠模型中检查了克林霉素（CLI）与自体奎酮（ATO）的联合作用。腹膜内感染了弓形虫RH株的10（2）或10（4）速殖子的Swiss Webster小鼠经口单独用两种药物经口处理（ATO剂量为5、25、50或100 mg / kg体重/天;对于CLI，则为25、50或400 mg / kg / day /天或两者结合使用（对于ATO和CLI，分别为5 + 25、25 + 25、25 + 50、50 + 50或100 + 400 mg / kg /天），从第1天开始持续14天。在7周内监测生存情况。通过代表性的4周幸存者的生物测定和通过PCR的代表性7周幸存者的寄生虫DNA检测来评估残留感染。与未治疗的对照小鼠相比，所有治疗组均显示出治疗效果（P = 0.0000）。在感染了10（2）寄生虫的小鼠中，任何剂量组合的ATO和CLI都比单独的ATO显着保护更多的动物（P = 0.0000），但与单独的CLI相比，鉴于其良好的效果，联合使用的药物不再有效（P > 0.05）。对于感染了10（4）寄生虫的小鼠，以最低和最高剂量（5加25和100加400 mg / kg /天）联合使用的药物比单独使用ATO更有效（分别为P = 0.035和0.000） ），而不仅仅是CLI（P> 0. 05）。但是，分别以25 mg / kg，25 mg +25、25 mg +50和50 mg +50 mg / kg /天的剂量使用ATO + CLI进行治疗，分别可保护20％，33％和78％的小鼠，相比之下，单独使用这两种药物治疗的小鼠几乎没有存活率（P <0.0005），因此证明了ATO和CLI对弓形虫的显着协同作用。此外，已显示给定CLI剂量的ATO剂量对效果至关重要。而且，在一些幸存者中没有残留感染表明该药物组合消除了寄生虫的潜力。

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