Efficacy of itraconazole as a combined continuous/pulse therapy in feline dermatophytosis: preliminary results in nine cases

This study evaluated the efficacy of itraconazole as a combined continuous/pulse therapy for feline dermatophytosis. Nine cats with dermatophytosis caused by Microsporum canis were treated with itraconazole at 10 mg kg(-1) orally once daily for 28 days and then on an alternate week regimen (1 week off, 1 week on) at the same dosage. Cats were re-evaluated by physical examination and fungal culture at days 28, 42, 56 and 70 if necessary. Treatment was stopped when two consecutive negative fungal cultures were obtained. Eight cats were cured after 56 days, with two negative cultures obtained at days 28 and 42. In one case, a positive culture was obtained at day 28, but negative cultures were achieved at days 42 and 56. This protocol appears to be effective in the treatment of feline dermatophytosis, although these preliminary results should be confirmed by a controlled study.     

Does agricultural use of azole fungicides contribute to resistance in the human pathogen Aspergillus fumigatus?

Azole resistance in human fungal pathogens has increased over the past twenty years, especially in immunocompromised patients. Similarities between medical and agricultural azoles, and extensive azole (14α‐demethylase inhibitor, DMI) use in crop protection, prompted speculation that resistance in patients with aspergillosis originated in the environment. Aspergillus species, and especially Aspergillus fumigatus, are the largest cause of patient deaths from fungi. Azole levels in soils following crop spraying, and differences in sensitivity between medical and agricultural azoles (DMIs), indicate weaker selection in cropping systems than in patients receiving azole therapy. Most fungi have just one CYP51 paralogue (isozyme CYP51B), but in Aspergillus sp. mutations conferring azole resistance are largely confined to a second paralogue, CYP51A. Binding within the active centre is similar for medical and agricultural azoles but differences elsewhere between the two paralogues may ensure selection depends on the DMI used on crops. Two imidazoles, imazalil and prochloraz, have been widely used since the early 1970s, yet unlike triazoles they have not been linked to resistance in patients. Evidence that DMIs are the origin, or increase the frequency, of azole resistance in human fungal pathogens is lacking. Limiting DMI use would have serious impacts on disease control in many crops, and remove key tools in anti‐resistance strategies. © 2017 Society of Chemical Industry     

伊曲康唑肌肉注射液的药代动力学研究

以羟丙基-β-环糊精化合物做辅料对伊曲康唑分子进行包合,制成肌肉注射剂,以山羊为试验动物,用高效液相色谱-紫外检测器对伊曲康唑肌肉注射剂的药代动力学进行研究。结果表明,伊曲康唑肌肉注射后最高药物浓度(Cma)x为226.67ng·mL-1;达峰时间Tmax为3h;血药浓度-时间曲线面积(AUC)48h为0.33898×104ng·h-1·mL-1;血浆药物浓度维持时间357h。由此可知伊曲康唑包合剂肌肉注射后可以达到一定的有效血药浓度,可用于皮肤真菌病的治疗。     

Treatment of refractory feline sporotrichosis with a combination of intralesional amphotericin B and oral itraconazole

OBJECTIVE To describe the use of intralesional amphotericin B in localised lesions for the treatment of 26 cats from Rio de Janeiro, Brazil, with sporotrichosis refractory to oral itraconazole. DESIGN Uncontrolled intervention study. METHOD The 26 cats in this study were diagnosed with sporotrichosis, confirmed by isolation of Sporothrix schenckii, and presented residual localised skin lesions refractory to treatment with oral itraconazole for a minimum period of 8 weeks. The animals received weekly applications of intralesional amphotericin B in conjunction with oral itraconazole. In cases of owner unavailability, a maximum of 2 weeks between the infiltrations was accepted. RESULTS Twenty-two (84.6%) of the 26 treated cats achieved clinical remission, 16 (72.7%) of which were cured, and in the remaining six (27.3%) the lesions recurred at the same site. Lack of clinical response was observed in one animal and three owners abandoned treatment. CONCLUSION The proposed therapeutic regimen is an adjunctive treatment option for cats with sporotrichosis presenting as residual skin lesions refractory to itraconazole.     

3种真菌抗生素对绿僵菌和6种非目标真菌的生长影响分析

文章比较了两性霉素、伊曲康唑和放线菌酮对土壤内金龟子绿僵菌（Metarhizium anisopliae）、黄绿绿僵菌（M．flavoviride）和6种非目标真菌生长的影响。结果表明,伊曲康唑对毛霉（Mucor racemosus）和黑曲霉（Aspergillus niger）的抑菌效果较差,浓度达200μg／mL时对毛霉的抑制率仅达54．84％,且对绿僵菌生长的抑制作用显著大于两性霉素和放线菌酮（P＜0．01）,不适宜用于土壤绿僵菌的分离。两性霉素和放线菌酮在浓度为100μg／mL时,对6种非目标真菌抑制率达69％以上,可作为绿僵菌分离的真菌抗生素。     

An overview of antifungal drugs and their use for treatment of deep and superficial mycoses in animals

Fungal infections are often challenging to manage, given the limited numbers of therapeutics and a general lack of applicable clinical literature for their use in a given animal species. This article reviews some of the underlying principles that can affect the therapeutic outcome for a given antifungal, and provides specific information from the literature that is intended to highlight the distinctive properties of the most commonly used antifungals in veterinary medicine to better facilitate their successful application in clinical practice.     

Colorectal basidiobolomycosis in a dog

A 7-year-old castrated male French Bulldog was examined for chronic large intestinal enteropathy. A colonic mass and thickened rectal mucosa were identified, and histopathologic examination of endoscopic biopsy specimens disclosed eosinophilic proctitis with large (5-20 μm), irregularly shaped, pauciseptate hyphae that were Gomori methenamine silver and periodic acid-Schiff positive. Amplification and sequencing of ribosomal DNA extracted from paraffin-embedded tissues yielded a sequence with 97% identity to GenBank sequences for Basidiobolus ranarum. After itraconazole, terbinafine, and prednisone administration, clinical signs resolved rapidly, and sonographic lesions were largely absent after 6 weeks. Treatment was discontinued by the owner 15 weeks after diagnosis. Three weeks later, the dog collapsed acutely and was euthanized. Necropsy identified metastatic islet cell carcinoma and grossly unremarkable colorectal tissues. However, histopathology of the rectum disclosed multifocal submucosal granulomas with intralesional hyphae morphologically similar to those previously observed. This report is the first to describe medical treatment of gastrointestinal basidiobolomycosis in a dog.     

伊曲康唑纳米乳的制备及含量测定

【目的】研制伊曲康唑纳米乳并评价其质量,考察纳米乳中伊曲康唑含量。【方法】以伊曲康唑为主要活性成分,肉桂醛和乙酸乙酯为混合油相,EL-40为表面活性剂,异丙醇为助表面活性剂,通过绘制伪三元相图确定伊曲康唑纳米乳的最优配方。利用透射电子显微镜(TEM)、激光粒度分析仪等评价伊曲康唑纳米乳的质量,利用紫外分光光度计考察纳米乳中伊曲康唑含量。【结果】经筛选,伊曲康唑纳米乳配方中各物质的质量分数为:伊曲康唑1.24%,肉桂醛4.58%,乙酸乙酯4.58%,EL-40 24.44%,异丙醇12.17%,蒸馏水52.99%。在TEM下,伊曲康唑纳米乳乳滴为圆球形,分布均一,平均粒径为14.48nm,多分散系数(PDI)为0.014。制备出的纳米乳澄清透明、稳定性良好。测定伊曲康唑纳米乳中伊曲康唑含量的最佳波长为261nm,检测方法的专属性良好。【结论】伊曲康唑纳米乳稳定性好且制备工艺简单,用于测定伊曲康唑纳米乳中伊曲康唑含量的紫外分光光度法专属性好、精密度高。     

Plasma concentrations of itraconazole following a single oral dose in juvenile California sea lions (Zalophus californianus)

The objective of this study was to establish a single-dose pharmacokinetic profile for orally administered itraconazole in California sea lions (Zalophus californianus). Twenty healthy rehabilitated juvenile California sea lions were included in this study. Itraconazole capsules were administered orally with food at a target dose of 5–10 mg/kg. Blood samples were collected from each animal at 0 hr and at two of the following timepoints: 0.5, 1, 2, 4, 6, 8, 12, 24, 48, and 72 hr. Quantitative analysis of itraconazole in plasma samples was performed by high-performance liquid chromatography. An average maximum concentration of 0.22 µg/ml ± 0.11 was detected 4 hr after administration. The average concentration fell to 0.12 µg/ml ± 0.11 by 6 hr and 0.02 µg/ml ± 0.02 at 12 hr. At no point did concentrations reach 0.5 µg/ml, the concentration commonly accepted for therapeutic efficacy. While this formulation was well tolerated by the sea lions, oral absorption was poor and highly variable among individuals. These data indicate that a single oral dose of itraconazole given as a capsule at 5–10 mg/kg, under the conditions used in this study, does not achieve therapeutic plasma concentrations in California sea lions.     

伊曲康唑注射液对小白鼠LD50的测定和肝肾的影响

研究伊曲康唑注射液对小白鼠的半数致死量(LD50),将70只昆明纯种小白鼠随机分为7组,每组10只,在预试验基础上确定各组小鼠的用药量,采用改进的寇氏法测定小白鼠皮下注射伊曲康唑LD50;为研究伊曲康唑注射液对小白鼠肝肾指标的影响,将80只小白鼠随机分为4组,每组20只,采用背部皮下给药法,试验组按不同剂量连续给药1个月,对照组给予生理盐水,检测肝肾生化指标.结果测得LD50129.57 mg·kg-1,95%可信限106.66~157.40 mg·kg-1;高剂量组小白鼠GPT升高,与其他三组比较,差异显著(P<0.05).