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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Efficacies of high-dose fluconazole plus amphotericin B and high-dose fluconazole plus 5-fluorocytosine versus amphotericin B, fluconazole, and 5-fluorocytosine monotherapies in treatment of experimental endocarditis, endophthalmitis, and pyelonephri
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Efficacies of high-dose fluconazole plus amphotericin B and high-dose fluconazole plus 5-fluorocytosine versus amphotericin B, fluconazole, and 5-fluorocytosine monotherapies in treatment of experimental endocarditis, endophthalmitis, and pyelonephri

机译：大剂量氟康唑+两性霉素B和大剂量氟康唑+ 5-氟胞嘧啶与两性霉素B，氟康唑和5-氟胞嘧啶单一疗法在治疗心内膜炎，眼内炎和肾盂肾炎中的疗效

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We compared the efficacies of fluconazole (Flu), amphotericin B (AmB), and 5-fluorocytosine (5FC) monotherapies with the combination of Flu plus 5FC and Flu plus AmB in a rabbit model of Candida albicans endocarditis, endophthalmitis, and pyelonephritis. The dose of Flu used was that which resulted in an area under the concentration-time curve in rabbits equivalent to that seen in humans who receive Flu at 1,600 mg/day, the highest dose not associated with central nervous system toxicity in humans. Quantitative cultures of heart valve vegetations, the choroid-retina, vitreous humor, and kidney were conducted after 1, 5, 14, and 21 days of therapy. All untreated controls died within 6 days of infection; animals treated with 5FC monotherapy all died within 18 days. In contrast, 93% of animals in the other treatment groups appeared well and survived until they were sacrificed. At day 5, the relative decreases in CFU per gram in the vitreous humor were greater in groups that received Flu alone and in combination with 5FC or AmB than in groups receiving AmB or 5FC monotherapies (P < 0. 005) but were similar thereafter. In the choroid-retina, 5FC was the least-active drug. However, there were no differences in choroidal fungal densities between the other treatment groups. On days 5 and 14 of therapy, fungal densities in kidneys of AmB recipients were lower than those resulting from the other therapies (P < 0.001 and P < or = 0.038, respectively) and AmB-plus-Flu therapy was antagonistic; however, all therapies for fungal pyelonephritis were similar by treatment day 21. While fungal counts in cardiac valves of Flu recipients were similar to those of controls on day 5 of therapy and did not change from days 1 to 21, AmB therapy significantly decreased valvular CFUs versus Flu at days 5, 14, and 21 (P < 0.005 at each time point). 5FC plus Flu demonstrated enhanced killing in cardiac vegetations compared with Flu or 5FC as monotherapies (P < 0. 03). Similarly, the combination of AmB and Flu was more active than Flu in reducing the fungal density in cardiac vegetations (P < 0.03). However, as in the kidney, AmB plus Flu demonstrated antagonism versus AmB monotherapy in the treatment of C. albicans endocarditis (P < 0.05, P = 0.036, and P < 0.008 on days 5, 14, and 21, respectively).
机译：我们在白色念珠菌心内膜炎，眼内炎和肾盂肾炎的兔子模型中比较了氟康唑（Flu），两性霉素B（AmB）和5-氟胞嘧啶（5FC）单一疗法与Flu加5FC和Flu加AmB联合治疗的疗效。使用的流感剂量是在兔子的浓度-时间曲线下产生的面积，相当于在接受1600毫克/天的流感的人类中看到的面积，这是与人类中枢神经系统毒性无关的最高剂量。治疗1、5、14和21天后进行心脏瓣膜植被，脉络膜视网膜，玻璃体液和肾脏的定量培养。所有未经治疗的对照在感染后6天内死亡; 5FC单药治疗的动物在18天内全部死亡。相反，在其他治疗组中，有93％的动物表现良好并存活直至被处死。在第5天，单独接受Flu并与5FC或AmB联合使用的组的玻璃体液中每克CFU的相对降低要大于接受AmB或5FC单一疗法的组（P <0. 005），但此后相似。在脉络膜视网膜中，5FC是活性最低的药物。但是，其他治疗组之间的脉络膜真菌密度没有差异。在治疗的第5天和第14天，AmB受体的肾脏中的真菌密度低于其他疗法所致的密度（分别为P <0.001和P <或= 0.038），并且AmB-plus-Flu治疗具有拮抗作用。然而，在治疗的第21天，所有真菌性肾盂肾炎的治疗方法均相似。尽管流感受体的心脏瓣膜中的真菌计数在治疗的第5天与对照组相似，并且从第1天到第21天没有变化，但AmB治疗显着降低了瓣膜CFU与第5、14和21天的流感相比（每个时间点P <0.005）。与单一疗法Flu或5FC相比，5FC加Flu证明对心脏植被的杀灭作用增强（P <0. 03）。同样，AmB和Flu的组合在降低心脏植被中的真菌密度方面比Flu更有效（P <0.03）。但是，与肾脏一样，AmB加Flu在白色念珠菌心内膜炎的治疗中显示出与AmB单药疗法的拮抗作用（分别在第5、14和21天分别为P <0.05，P = 0.036和P <0.008）。

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