In vitro amoebicidal activity of propamidine and pentamidine isethionate against Acanthamoeba species and toxicity to corneal tissues
In vitro amoebicidal activity of propamidine and pentamidine isethionate against Acanthamoeba species and toxicity to corneal tissues
复制标题
DOI：
10.1097/00003226-199701000-00016
复制
发表时间：
1997-01-01
期刊：
影响因子：
2.8
通讯作者：
McCulley, JP
中科院分区：
文献类型：
--
作者：
Alizadeh, H;Silvany, RE;McCulley, JP
棘阿米巴角膜炎的有效化疗一直受到阻碍，因为寄生虫对各种抗菌药物具有明显的耐药性。鉴于目前在欧洲外用溴丙烯（异硫代丙脒）和新孢菌素被认为是治疗的选择，我们试图确定喷他脒是否同样有效，因为美国眼科医生更容易获得这种药物。在这项研究中，我们比较了溴烯（商品）、异硫丙脒和异硫戊脒（Pentam）对三种不同棘阿米巴的体外杀阿米巴活性，以及药物与兔角膜上皮和内皮细胞培养物的生物相容性。结果表明，不同物种对药物的敏感性存在显著差异。丙脒（>0,000 μ g/ml）对黄颡鱼的药效明显低于喷他脒（>,125 μ g/ml），但对食蚜螨的药效相当（>,250 μ g/ml）。另一方面，丙脒（>31.25 μ g/ml）的药效略高于喷他脒（>62.5 μ g/ml）。这两种药物在与细胞培养物短期接触后也相对无毒，即使高浓度的喷他脒对浅表上皮造成轻度损伤，对内皮造成可逆性膜损伤。然而，在有效的杀阿米巴浓度下，丙帕脒的稳态水平比喷他脒的毒性大得多，这表明该药的治疗指数要低得多。我们的数据表明，喷他脒可能是一种有效的治疗选择，因为它的效力和低毒性。
Effective chemotherapy for Acanthamoeba keratitis has been hampered because of the marked resistance of the parasites to a variety of antimicrobial agents. In view of the fact that topical Brolene (propamidine isethionate) and neosporin are currently considered to be the medical treatment of choice in Europe, we sought to determine whether pentamidine may be equally effective, because the drug is more readily available to ophthalmologists in the United States. In this study, we compared the amoebicidal activity of the Brolene (commercial product), propamidine isethionate and pentamidine isethionate (Pentam) in vitro against three different species of Acanthamoeba, and the drugs' corresponding biocompatibility with rabbit corneal epithelial and endothelial cell cultures. The results indicated that there were significant species differences in drug sensitivity. Propamidine (>1,000 mu g/ml) was clearly less effective than pentamidine (>125 mu g/ml) against A. castellanii, although equivalent potency (>250 mu g/ml) was observed against A. polyphaga. On the other hand, propamidine (>31.25 mu g/ml) was slightly more effective than pentamidine (>62.5 mu g/ml) against A. hatchetti. Both drugs were also relatively nontoxic after short-term contact with cell cultures, even though the highest concentration of pentamidine caused low-grade injury to the superficial epithelium and reversible membrane damage to the endothelium. Steady-state levels of propamidine at effective amoebicidal concentrations, however, were much more toxic than pentamidine, which indicated that the drug has a much lower therapeutic index. Our data suggest that pentamidine may be an effective therapeutic option because of its potency and low toxicity.