Euxyl K 400: a new sensitizer in cosmetics

A case of allergic contact dermatitis from miconazole is reported. Patch testing with a series of azole antimycotics was positive only to miconazole, isoconazole, tioconazole and oxiconazole. Those reacting are all beta-substituted 1-phenethyl imidazoles with an ortho-chlorine substitution on the aromatic ring. For this hitherto unreported pattern of cross-sensitivity, the designation of "ortho-chloro cross-sensitivity" is proposed.     

Contact allergy to imidazole antimycotics

Between 1977 and 1986, 9 patients with contact allergy to the active ingredient of imidazole antimycotics were found at the Department of Dermatology, University of Heidelberg. The number of positive reactions decreased in the following order: miconazole (6), clotrimazole (3), econazole (3), isconazole (3), and oxiconazole (1). When 5 patients were tested with a series of imidazoles in different concentrations and vehicles (petrolatum, ethyl methyl ketone, ethanol), petrolatum turned out to be the least effective one. The active ingredient at 1% in ethanol seems to be the most suitable choice for routine patch testing. Bifonazole may be the therapeutic alternative for patients sensitive to miconazole or clotrimazole, since no cross reactivity was observed.     

Comparison of econazole and isoconazole as single dose treatment for vaginal candidosis.

In a single blind trial there was no significant difference between econazole (2 X 150 mg pessaries) and isoconazole (2 X 300 mg pessaries) given as a once only treatment for vaginal candidosis. Cure rates at 14 days were 70.4% for econazole and 77.6% for isoconazole, and at 28 days were 63.8% and 64.5% respectively. Though isoconazole was formulated for single dose usage, econazole was formulated for a regimen of one pessary a night for three nights.     

性病门诊病人阴道念珠菌的菌种分布和耐药性检测

目的：了解性病门诊病人阴道念珠菌病的菌种分布和耐药性情况。方法：收集性病门诊病人阴道念珠菌85株，采用常规方法及API 20C AUX试验条方法鉴定念珠菌的种类，耐药性的检测采用ATB FUNGS方法测定念珠菌对6种抗真菌药物的耐药性。结果：85株念珠菌以白念珠菌为主，检出67株，占79％，其次为光滑念珠菌，占9．4％。念珠菌对两性霉素B、制霉菌素、5-氟胞嘧啶、咪康唑、酮康唑和益康唑的敏感率分别为94．1％、94．1％、85．9％、56．7％、55．3％和50．1％。结论：性病门诊病人阴道念珠菌以白念珠菌为主，对两性霉素B、制霉菌素和5-氟胞嘧啶敏感性高，对咪康唑、酮康唑和益康唑的耐药性高。     

Topical Pharmacology of Imidazole Antifungals

Four imidazole derivatives have now undergone extensive open and comparative trials as topical agents in dermatomycoses and vaginal candidosis. They are chlormidazole (Chemie Grünenthal), clotrimazole (Bayer), miconazole (Janssen) and econazole (Janssen, CilagChemie); all also have some antibacterial activity. Many other imidazoles have been marketed, usually as antiprotozoal or anthelminthic agents, and some of these have some anti-mycotic activity as well as other miscellaneous therapeutic properties. The mode of action of imidazole antimycotic agents is discussed; after prolonged topical application to animals and human subjects, systemic absorption is negligible. All four agents which are available as cream, powder, lotion or vaginal tablets have many successful studies to their credit, often with clinical and mycological cure rates of over 80 % in a variety of dermatomycoses and in vaginal candidosis. The relative value of these topical agents is discussed, and it is suggested that in severe and extensive dermatomycoses consideration should be given to the systemic use of miconazole in support of topical therapy.     

卢立康唑等七种咪唑类抗真菌药物对常见念珠菌的体外活性检测

【摘要】 目的 评价卢立康唑等7种咪唑类药物对临床分离常见念珠菌的体外敏感性。方法 参考美国临床实验室标准化研究所（CLSI）的微量稀释法M27-A3方案,检测5种共183株临床分离念珠菌对卢立康唑、酮康唑、咪康唑、益康唑、克霉唑、舍他康唑、联苯苄唑7种咪唑类药物的体外敏感性。结果 酮康唑、咪康唑、益康唑、克霉唑、舍他康唑和联苯苄唑的体外最低抑菌浓度（MIC）范围（几何均数）分别为0.03 ～ 8（0.067）、0.03 ～ 16（0.071）、0.03 ～ 8（0.207）、0.03 ～ 8（0.061）、0.03 ～ 16（0.187）和0.03 ～ ＞ 16（1.050） mg/L。卢立康唑对5种念珠菌均有较好的体外敏感性,MIC范围0.03 ～ 8 mg/L ,几何均数为0.087 mg/L,MIC50和MIC90分别为0.06 mg/L和0.5 mg/L。包括卢立康唑在内,各受试药物均有部分相对不敏感菌株。结论 除联苯苄唑外,其他6种咪唑类药物均对念珠菌有良好的体外抗菌活性,但存在少数相对不敏感菌株。     

Pityrosporum (Malassezia) folliculitis in Saudi Arabia—diagnosis and therapeutic trials

Pityrosporum folliculitis (PF) is frequently misdiagnosed as acne vulgaris, resulting in unnecessary and prolonged treatment. Sixty-two patients with PF seen in the Dermatology Clinic, King Gahad Hofuf Hospital, Saudi Arabia were evaluated clinically. The diagnosis was confirmed by routine histology with haemotoxylineosin eosin Staining and Periodic acid-Schiff staining. Scrapings of the lesions, especially the molluscum-like papules, were mounted in KOH/Parker blue ink and examined under the microscope. Patients, divided into three groups as follows, were given treatment: for 4 weeks: (I) 20 were treated with ketoconazole, 200 mg orally in addition to ketoconazole shampoo 2% daily (2) 20 were given only ketoconazole, 200mg daily, orally; (3) 12 used econazole nitrate 1% solution applied twice daily; and (4) 10 used miconazole nitrate 2% cream twice daily. (uses in groups 3 and 4, w ho did not respond, were given the same treatment as for group 1. All who responded were kept on ketoconaxolc shampoo 2% twice weekly. PF was commoner in young adult females as the female lo male ratio was 2:1 while the mean age was 21·5 years. The most common site involved was the trunk (95%) in the form of papules, pustules and molluscoid lesions. The latter type of lesion yielded the highest number of spores using KOH/Parker blue ink. Biopsy was positive in 87% of the patients but is usually not necessary. Combined topical and systemic ketoconazole produced clearance of the lesions in 20 patients (100%), while systemic therapy only resulted in 75% clearance (15 of 20). Topical econazolc and miconazole failed in 20 of 22 (90%) and improved only two patients. There were no significant side-effects from the drugs.     

高危人群阴道念珠菌带菌情况及抗真菌药物药敏分析

目的：为了解性病高危人群酵母菌的带菌情况和和对抗真菌药物的敏感性，方法：对167例特殊职业的性病高危女性人群进行了阴道分泌物涂片及培养检测，对分离出的临床菌株进行了8种常用抗真菌药物的敏感性检测。结果：性病高危女性人群中阴道念珠菌带菌率为12．1％，优势主要菌株仍以白念珠菌为主。结论：伊曲康唑、氟康唑，二性霉素B，制霉菌素，益康唑，酮康唑，咪康唑和5－氟胞啶的的药物敏感性显示，前4种均属高度敏感，后4种药物有不同程度的中度敏感与耐药。     

Pustular allergic contact dermatitis to isoconazole nitrate

The topical imidazole antimycotics are widely used and are an infrequent cause of contact allergy. We report on a woman, who developed an unusual clinical picture of allergic contact dermatitis, namely papulopustular reaction, evoked by an isoconazole nitrate-containing cream. The histopathologic changes included subcorneal pustules, spongiosis, and an inflammatory infiltrate composed mainly of lymphocytes and some eosinophils and neutrophils. The patient demonstrated a severe vesicular reaction to isoconzole nitrate as is and at an imidazoles concentration of 0.5%. No cross-reactivity with other imidazole antimycotics was noted.     

Therapy of opportunistic mycoses]

The author presents the drugs that are available for the treatment of opportunistic mycoses: amphotericin B, nystatin, 5-fluorocytosine, miconazole and the newest imidazole derivative econazole. He presents his experience with econazole in 4 cases with deep mycoses. He speaks of the mode of application and the therapeutical limits of these products as well as of the favorable factors and the prophylactic measures to be taken.     

Selective calmodulin antagonists fail to inhibit phorbol ester-induced superoxide anion release from human neutrophils: effects of antifungal azole derivatives

Summary The ability of antifungal azole derivatives to inhibit superoxide anion release from human leucocytes and the relevance of their documented calmodulin (CaM) antagonism was investigated with respect to anti-inflammatory drug activity. Econazole, miconazole and clotrimazole were found to inhibit phorbol ester-induced release of superoxide anions from human polymurphonuclear leucocytes effectively with IC₅₀ values in the range of 36–162 μmol/1. In contrast, bifonazole and ketoconazole produced minimal or no inhibition, thus suggesting that mechanisms other than inhibition of superoxide anion release may largely account for their clinical activity in inflammatory skin disorders. The selective CaM antagonist J-8, which was used as a reference, failed to inhibit the release process, whereas W-7 as a dual CaM/protein kinase C inhibitor induced dose-dependent inhibition. When tested on protein kinuse C activity in vitro , econazole, miconazole and clotrimazole were inhibitory, but bifonazole and ketoconazole were without significant effect. It is thus concluded that inhibition of superoxide anion release reflects the ability of these drugs to inhibit protein kinase C, but not their potency to antagonize CaM. Given the role of reactive oxygen species in lissue damage hy neutrophils. we propose protein kinase C, rather than CaM, as another potential target of anti-inflammatory therapy.     

婴幼儿皮肤念珠菌病的致病菌株及药敏试验分析

目的 分析婴幼儿皮肤念珠菌病的致病菌种类及对抗真菌药物的敏感性。方法 收集皮肤念珠菌病患儿病例，对临床分离的致病菌进行常规菌种鉴定，采用琼脂稀释法（药基法）对临床分离的念珠菌进行6种药物（氟康唑、咪康唑、联苯苄唑、益康唑、克霉唑、制霉菌素）敏感性试验，选取9株白念珠菌临床菌株和1株白念珠菌标准菌株，参考NCCLS M27-A推荐的微量液体稀释法界定琼脂稀释法的药敏分界点，分析耐药性。结果 共收集75例皮肤念珠菌病病例，分离到的88株念珠菌均为白念珠菌，用琼脂稀释法所测的MIC范围是：氟康唑1 ～ 256 mg/L，咪康唑0.25 ～ 64 mg/L，联苯苄唑0.5 ～ 64 mg/L，益康唑0.25 ～ 32 mg/L，克霉唑1 ～ 64 mg/L，制霉菌素0.5 ～ 32 mg/L。临床株对唑类药物均有耐药株出现，氟康唑1株，克霉唑4株，益康唑3株，咪康唑5株，联苯苄唑9株。结论 婴幼儿皮肤念珠菌病主要由白念珠菌引起；白念珠菌对5种唑类药物均有耐药株出现，且有交叉耐药现象，对制霉菌素敏感。     

Imidazoles and benzoyl peroxide: a comparative trial of two treatment schedules

A double-blind, split-face, self-controlled pilot trial was designed for comparing the therapeutical effect of (a) combination of 2% miconazole nitrate and 5% benzoyl peroxide applied twice daily and (b) topical application of 1% isoconazole nitrate in the morning followed in the evening by 5% benzoyl peroxide. There were no clinically relevant differences between both treatment regimes. These results are interpreted in terms of bioavailability of the active substances.     

Contact dermatitis to a canine anti-dandruff shampoo

A 40-year-old teacher presented after her third episode of acute facial oedema within 4 months. Each episode occurred 1-2 days after visiting her mother's house. Patch testing showed positive reactions to miconazole and econazole nitrate. The patient denied use of any antifungal creams, but it transpired that her mother's dog was being shampooed weekly with an antifungal shampoo containing miconazole. No further episodes were recorded after discontinuing the antifungal shampoo.     

Comparison of the in vitro antifungal activities of clotrimazole, miconazole, econazole and exalamide against clinical isolates of dermatophytes

The in vitro antifungal activities of clotrimazole, miconazole nitrate, econazole nitrate, and exalamide against 64 clinical isolates of various dermatophyte species obtained from out-patients seen at the Nippon Medical School Hospital were simultaneously compared using a liquid microculture method. The rank order of activity against the 64 isolates of dermatophytes was clotrimazole > econazole nitrate > miconazole nitrate > exalamide. For a given antimycotic, the minimal inhibitory concentration was affected by the dermatophyte species.     

Anthralin is a potent inhibitor of pityrosporum orbiculare/ovale in vitro.

Two strains of Pityrosporum orbiculare/ovale were grown in a liquid medium and exposed to different concentrations of the imidazoles ketoconazole and clotrimazole as well as anthralin, liquor carbonis detergens and salicylic acid. With regard to growth inhibition of yeast cells, the efficacies of anthralin and the imidazoles were similar, a half-maximal inhibition being achieved with an anthralin concentration of 7 mg/l. Liquor carbonis detergens and salicylic acid also inhibited growth of Pityrosporum orbiculare/ovale, but only at much higher concentrations. The response to salicylic acid was mainly due to its acid pH.     

Anti-inflammatory and anti-itch activity of sertaconazole nitrate

Cutaneous fungal infections are frequently associated with an inflammatory component including irritated skin, itching and stinging/burning. Therapeutic anti-fungal agents that have anti-inflammatory activity have the potential to provide clinical benefit beyond fungus eradication. Recently, certain anti-fungal agents have been shown to have intrinsic anti-inflammatory activity, therefore we sought to determine the extent of the anti-inflammatory activity of these compounds. The anti-inflammatory activities of eight anti-fungal agents (butoconazole, ciclopirox olamine, fluconazole, miconazole nitrate, sertaconazole nitrate, terconazole, tioconazole and ketoconazole) were compared in a number of preclinical models of dermal inflammation and pruritus. While butoconazole, ciclopirox olamine, fluconazole, and miconazole nitrate were all found to have anti-inflammatory activity, only sertaconazole nitrate reduced the release of cytokines from activated lymphocytes and mitigated inflammation in animal models of irritant contact dermatitis and neurogenic inflammation. In addition, sertaconazole nitrate inhibited contact hypersensitivity and scratching responses in a murine model of pruritus. Furthermore, the in vitro and in vivo anti-inflammatory activity of sertaconazole nitrate was found to be greater than other topical anti-fungal agents examined. These studies demonstrate that topical administration of clinically relevant concentrations of sertaconazole nitrate resulted in an efficacious anti-inflammatory activity against a broad spectrum of dermal inflammation models and itch. The anti-inflammatory properties of sertaconazole may contribute to the efficacy of the drug in the treatment of cutaneous fungal conditions and provide greater anti-inflammatory activity compared with other anti-fungal agents.     

Widespread Candida folliculitis in a nontoxic patient.

We present a case of widespread Candida folliculitis in a nontoxic, immunocompetent woman. Predisposing factors included obesity and use of systemic antibiotics and topical steroids. Diagnosis was made through potassium hydroxide and Gram's stain examination of the pustular contents. The patient was treated with oral ketoconazole and topical econazole, with resolution of the eruption in six weeks. We suggest that temperature played a role in the follicular location of the lesions.     

The activity in vitro of five different antimycotics against Pityrosporum orbiculare.

The activity in vitro of miconazole, clotrimazole, econazole, sodium omadine, and sodium thiosulphate against Pityrosporum orbiculare was found to correlate with the good clinical results these drugs produce in tinea versicolor. In addition many substances used as solvents or in vehicles had an inhibitory effect in vitro against P. orbiculare. The influence of the culture medium, especially lipids, on the action of imidazole derivatives is discussed.