EA3800 'Protozooses Transmises par l'Alimentation' - University of Rouen Normandy, Rouen, France.
Department of Ophthalmology - Charles Nicolle University Hospital, Rouen, France.
J Antimicrob Chemother. 2018 Jul 1;73(7):1895-1898. doi: 10.1093/jac/dky094.
Acanthamoeba keratitis (AK) is a sight-threatening infectious disease. Its effective and safe medical therapy remains highly debated. Recently, voriconazole, a monotriazole with noted in vitro activity against a large variety of fungi, has been successfully used both topically and systemically to treat human AK cases.
To measure anti-Acanthamoeba polyphaga in vitro activity, anti-rat AK efficiency and rat cornea penetration of eye-drop and oral voriconazole.
A. polyphaga was maintained in axenic cultures. In vitro, amoebicidal and cysticidal activities of voriconazole were measured using an XTT assay. AK lesions of Sprague Dawley rats were scored from grade 0 to grade 3. For 21 days, from day 7 post-infection, voriconazole (1% solution) eye drops were instilled or voriconazole was administered by gavage (60 mg/kg/day). After killing, superficial corneal epithelium scrapings were cultured and analysed by PCR, and eye-globe histology was performed. Cornea and plasma concentrations were determined using 2D HPLC separation and tandem MS.
In vitro, voriconazole inhibited trophozoite proliferation with an IC50 value of 0.02 mg/L and an IC90 value of 2.86 mg/L; no cysticidal effect was found. In AK rats, eye drops reduced clinical worsening from day 7 to day 14 post-infection and oral voriconazole was not effective. Voriconazole cornea concentrations were directly dependent on the frequency of eye-drop instillations, which resulted in lower plasma concentrations, whilst oral voriconazole resulted in lower cornea concentrations.
Present data underline the need for high-frequency eye-drop instillation regimens for efficient AK therapy.
棘阿米巴角膜炎（AK）是一种威胁视力的传染病。其有效且安全的医学治疗方法仍存在很大争议。最近，伏立康唑，一种具有显著体外抗真菌活性的单三唑，已成功地用于局部和全身治疗人类 AK 病例。
测量伏立康唑体外抗 Polyphaga acanthamoeba 的活性、抗大鼠 AK 的效率以及滴眼和口服伏立康唑在大鼠角膜中的穿透性。
Acanthamoeba polyphaga 在无共生培养中维持。在体外，使用 XTT 测定法测定伏立康唑的杀阿米巴和杀囊作用。使用 Sprague Dawley 大鼠 AK 病变评分从 0 级到 3 级。从感染后第 7 天开始，21 天内，每天用伏立康唑（1%溶液）滴眼或口服伏立康唑（60mg/kg/天）。处死时，通过 PCR 对浅层角膜上皮刮片进行培养和分析，并进行眼球组织学检查。使用 2D HPLC 分离和串联 MS 测定角膜和血浆浓度。
体外，伏立康唑抑制滋养体增殖，IC50 值为 0.02mg/L，IC90 值为 2.86mg/L；未发现杀囊作用。在 AK 大鼠中，滴眼从感染后第 7 天到第 14 天减少了临床恶化，口服伏立康唑无效。伏立康唑的角膜浓度直接取决于滴眼的频率，这导致较低的血浆浓度，而口服伏立康唑导致较低的角膜浓度。
目前的数据强调了需要高频滴眼滴注方案来有效治疗 AK。
