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局部抗菌治疗的机会:夫西地酸对犬皮肤的渗透

Opportunities for topical antimicrobial therapy: permeation of canine skin by fusidic acid.

作者信息

Frosini Sian-Marie, Bond Ross, Loeffler Anette, Larner Jo

机构信息

Department of Clinical Sciences and Services, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield, UK.

Research Centre for Topical Drug Delivery and Toxicology, Department of Pharmacy, Pharmacology & Postgraduate Medicine, University of Hertfordshire, Hatfield, UK.

出版信息

BMC Vet Res. 2017 Nov 21;13(1):345. doi: 10.1186/s12917-017-1270-6.

Abstract

BACKGROUND

Staphylococcal infection of the canine epidermis and hair follicle is amongst the commonest reasons for antimicrobial prescribing in small animal veterinary practice. Topical therapy with fusidic acid (FA) is an attractive alternative to systemic therapy based on low minimum inhibitory concentrations (MICs, commonly <0.03 mg/l) documented in canine pathogenic staphylococci, including strains of MRSA and MRSP (methicillin-resistant Staphylococcus aureus and S. pseudintermedius). However, permeation of canine skin by FA has not been evaluated in detail. This study aimed to define the degree and extent of FA permeation in canine skin in vitro from two sites with different hair follicle density following application of a licensed ophthalmic formulation that shares the same vehicle as an FA-betamethasone combination product approved for dermal application in dogs. Topical FA application was modelled using skin held in Franz-type diffusion cells. Concentrations of FA in surface swabs, receptor fluid, and transverse skin sections of defined anatomical depth were determined using high-performance liquid chromatography and ultraviolet (HPLC-UV) analysis.

RESULTS

The majority of FA was recovered by surface swabs after 24 h, as expected (mean ± SEM: 76.0 ± 17.0%). FA was detected within 424/470 (90%) groups of serial sections of transversely cryotomed skin containing follicular infundibula, but never in 48/48 (100%) groups of sections containing only deeper follicular structures, nor in receptor fluid, suggesting that FA does not permeate beyond the infundibulum. The FA concentration (mean ± SEM) in the most superficial 240 μm of skin was 2000 ± 815 μg/g.

CONCLUSIONS

Topically applied FA can greatly exceed MICs for canine pathogenic staphylococci at the most common sites of infection. Topical FA therapy should now be evaluated using available formulations in vivo as an alternative to systemic therapy for canine superficial bacterial folliculitis.

摘要

背景

犬表皮和毛囊的葡萄球菌感染是小动物兽医实践中使用抗菌药物最常见的原因之一。基于犬致病性葡萄球菌(包括耐甲氧西林金黄色葡萄球菌和耐甲氧西林中间型葡萄球菌菌株)中记录的低最低抑菌浓度(MIC,通常<0.03mg/l),用夫西地酸(FA)进行局部治疗是全身治疗的一种有吸引力的替代方法。然而,FA对犬皮肤的渗透尚未得到详细评估。本研究旨在通过使用与批准用于犬皮肤的FA-倍他米松组合产品具有相同赋形剂的许可眼科制剂,在体外确定FA在犬皮肤中从两个毛囊密度不同的部位的渗透程度和范围。使用置于Franz型扩散池中皮肤模拟局部应用FA。使用高效液相色谱和紫外线(HPLC-UV)分析测定表面拭子、受体液和确定解剖深度的横向皮肤切片中FA的浓度。

结果

如预期的那样,24小时后大部分FA通过表面拭子回收(平均值±标准误:76.0±17.0%)。在470个包含毛囊漏斗部的横向冷冻切片的连续切片组中的424组(90%)中检测到了FA,但在48个仅包含更深毛囊结构的切片组中的48组(100%)中以及受体液中均未检测到,这表明FA不会渗透到漏斗部以外。皮肤最表层240μm处的FA浓度(平均值±标准误)为2000±815μg/g。

结论

局部应用的FA在最常见的感染部位可大大超过犬致病性葡萄球菌的MIC。现在应该使用现有的制剂在体内评估局部FA治疗作为犬浅表细菌性毛囊炎全身治疗的替代方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0215/5697365/daa729ab5fcd/12917_2017_1270_Fig1_HTML.jpg

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