Fosmidomycin-clindamycin for plasmodium falciparum infections in African children
Fosmidomycin-clindamycin for plasmodium falciparum infections in African children
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DOI：
10.1086/381785
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发表时间：
2004-03-01
影响因子：
6.4
通讯作者：
Kremsner, PG
中科院分区：
文献类型：
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作者：
Borrmann, S;Adegnika, AA;Kremsner, PG
背景磷霉素是一种作用机制新颖的抗疟新药。在非洲进行的评价磷咪霉素作为单药治疗的研究表明其具有极好的耐受性，但需要每日3次治疗方案，治疗时间大于或等于4天，才能实现根治，这促使进一步研究以确定和验证合适的联合伙伴，以提高其疗效。我们进行了一项随机、对照、开放性研究，以评价磷司米霉素与克林霉素联合用药的疗效和安全性（n = 12;分别为30和5 mg/kg体重，每12 h一次，持续5天），与磷咪霉素单独给药相比（n = 12; 30 mg/kg体重，每12 h一次，持续5天）和克林霉素单独给药（n = 12; 5毫克/公斤体重，每12小时一次，持续5天），以清除加蓬7- 10岁学龄儿童的无症状恶性疟原虫感染。14年，成绩。在接受磷司米霉素-克林霉素（中位时间，18小时）和单独使用磷司米霉素（25小时）治疗的儿童中，无性寄生虫被迅速清除，但在单独使用克林霉素治疗的儿童中，无性寄生虫被缓慢清除（71小时; P = 0.004）。然而，仅用磷咪霉素-克林霉素或克林霉素单独治疗导致无性寄生虫的彻底消除，如通过100%的第14天和第28天治愈率所测量的。7名接受磷霉素治疗的儿童在第28天再次出现无性寄生虫（第14天治愈率为92% [11/12];第28天治愈率为42% [5/12]）。所有方案均耐受良好，无严重不良事件发生。磷司米多霉素和克林霉素的组合耐受性良好，并且在快速和彻底清除非洲儿童恶性疟原虫感染方面上级单独使用任何一种药物。
Background. Fosmidomycin is a new antimalarial drug with a novel mechanism of action. Studies in Africa that have evaluated fosmidomycin as monotherapeutic agent demonstrated its excellent tolerance, but 3-times-daily treatment regimens of greater than or equal to4 days were required to achieve radical cure, prompting further research to identify and validate a suitable combination partner to enhance its efficacy.Methods. We conducted a randomized, controlled, open-label study to evaluate the efficacy and safety of fosmidomycin combined with clindamycin (n = 12; 30 and 5 mg/kg body weight every 12 h for 5 days, respectively), compared with fosmidomycin alone (n = 12; 30 mg/kg body weight every 12 h for 5 days) and clindamycin alone (n = 12; 5 mg/kg body weight every 12 h for 5 days) for the clearance of asymptomatic Plasmodium falciparum infections in schoolchildren in Gabon aged 7-14 years.Results. Asexual parasites were rapidly cleared in children treated with fosmidomycin-clindamycin (median time, 18 h) and fosmidomycin alone (25 h) but slowly in children treated with clindamycin alone (71 h; P = .004). However, only treatment with fosmidomycin-clindamycin or clindamycin alone led to the radical elimination of asexual parasites as measured by day 14 and 28 cure rates of 100%. Asexual parasites reappeared by day 28 in 7 children who received fosmidomycin (day 14 cure rate, 92% [11/12; day 28 cure rate, 42% [5/12]). All regimens were well tolerated, and no serious adverse events occurred.Conclusion. The combination of fosmidomycin and clindamycin is well tolerated and superior to either agent on its own with respect to the rapid and radical clearance of P. falciparum infections in African children.