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。     

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。     

Evaluation of in vitro activity of ciclopirox olamine,butenafine HCl and econazole nitrate against dermatophytes,yeasts and bacteria

Background In many instances, a cutaneous fungal infection may exist concomitantly with bacterial involvement. In this study we compared the in vitro activity of three antifungal agents against the dermatophytes, yeasts and bacteria recovered most commonly from cutaneous mycoses and bacterial infections. Methods Using a microdilution method adapted from the National Committee for Clinical Laboratory Standards (NCCLS), we determined the minimum inhibitory concentrations (MICs) of ciclopirox olamine, econazole nitrate and butenafine HCl against a panel of dermatophyte fungi and yeasts (n = 39) and bacterial isolates (n = 45). Results All three antifungals demonstrated comparable activity against the dermatophytes tested, with a MIC range of 0.03–0.25 µg/ml for ciclopirox, < 0.001–0.25 µg/ml for econazole and 0.03–0.25 µg/ml for butenafine. For yeasts, ciclopirox showed activity against all isolates, with an MIC range of 0.001–0.25 µg/ml, whereas econazole had a broader range of 0.125–> 0.5 µg/ml. Butenafine displayed limited activity against the yeast Candida albicans and no activity against Malassezia furfur. For the antibacterial activity studies, ciclopirox demonstrated activity against all isolates tested with a range of 0.06–2 µg/ml, while econazole showed activity against Gram‐positive bacteria only, with a MIC range of 0.004–0.25 µg/ml. Butenafine HCl had a limited activity against bacterial isolates tested, showing activity against β‐hemolytic Streptococcus Group A and Corynebacterium only. Neither econazole nitrate nor butenafine HCl demonstrated activity against any of the Gram‐negative strains evaluated in this study. Conclusions The data suggest that ciclopirox olamine has the broadest in vitro activity, in comparison to econazole and butenafine HCl, against bacteria, yeasts and bacteria. These findings may have implications in the use of these antimycotics in the treatment of mixed cutaneous infections where bacteria or yeasts are present in addition to dermatophytes.     

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.     

In vitro and in vivo cutaneous penetration and antifungal activity of naftifine

The topical antifungal agent naftifine has shown considerable potency against a broad spectrum of dermatophytes. In this study, an in vitro penetration test in human cadaver skin and an in vivo tape-stripping test were used to evaluate the penetration and antifungal activity of naftifine gel 1 percent and naftifine cream 1 percent compared with other antifungal agents. In both models, Trichophyton rubrum and T. mentagrophytes were the fungal species. Results show that naftifine gel 1 percent and naftifine cream 1 percent, in vitro and in vivo, penetrate the stratum corneum in concentrations that inhibit the growth of both fungal species. Following penetration in vitro, naftifine gel and cream were significantly more active against T. rubrum than econazole nitrate cream 1 percent. Following penetration in vivo, naftifine gel and cream were as active as econazole nitrate cream 1 percent and clotrimazole cream 1 percent against T. rubrum and T. mentagrophytes.     

The antibacterial efficacy of econazole nitrate in interdigital toe web infections

Twenty-four patients with severe interdigital toe web infections and no evidence of dermatophyte colonization received randomized treatment with either econazole nitrate (Spectazole) or its vehicle. Of the patients treated with econazole nitrate, 88% had good to excellent responses, whereas no patient treated with the vehicle showed improvement. The total aerobic flora in the econazole group decreased 93%, with decreases in the large-colony diphtheroids, lipophilic diphtheroids, and gram-negative bacteria. The results of this study demonstrate that the antibacterial activity of econazole nitrate makes it an effective agent for the treatment of severe interdigital bacterial infections uncomplicated by dermatophyte colonization.     

Contact allergy to imidazoles used as antimycotic agents

The present article reviews the literature (up to 1994) on contact sensitivity to imidazoles and presents the results obtained from 15 patients observed at the Contact Allergy Unit in Leuven. The frequency as well as the cross-reaction patterns described are analyzed. Although allergic contact reactions may have been missed in the past (mainly because of problems with the correct choice of vehicle for patch testing), they seem to be relatively infrequent in view of their widespread use. The imidazole derivatives most frequently reported 10 be allergens are miconazole, econazole, tiocanozole, and isoconazole. As far as cross-reactivity is concerned, statistically significant associations were found in the patient data between miconazole, econazole, and isoconazole: between isoconazole and miconazole and econazole: and also between isoconazole and tioconazole. Patients sensitive to phenylethyl imidazoles (except ketoconazole) needing antimycotic therapy should be advised to use ketoconazole, clotrimazole, bifonazole, or, perhaps, the new flutrimazole. Clearly, non-imidazole antifungals can also be used.     

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。     

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.     

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.     

Epidemiology and in vitro activity of antimycotics against candidal vaginal/skin/nail infections in Singapore

BackgroundCandidal infections of the skin/nails and vagina are very common worldwide. Various in vitro test systems are available to help to determine the antifungal activity of drugs. The minimum inhibitory concentration (MIC) is a standard measure of the in vitro potency of drugs against yeasts. MethodsVaginal smears and skin/nail scrapings of 50 consecutive patients with candidal vaginitis and 46 consecutive patients (28 women, 18 men) with cutaneous/nail candidosis were used in the study. Direct microscopy and culture from vaginal smears and skin scrapings were performed on all patients. The MICs were determined using the broth dilution method. ResultsFor vaginal candidosis, the mean age of the patients was 28.2 years (range, 9–49 years). Candida albicans accounted for 58% of the isolates, C. glabrata for 32%, C. tropicalis for 6%, and C. parasilosis for 4%. At the MIC of 4 mg/L, 65–95% of C. albicans, 66–94% of C. glabrata, 33–100% of C. tropicalis, and 0–50% of C. parasilosis were susceptible to the drugs tested (ketoconazole, itraconazole, nystatin, amorolfine, clotrimazole, and miconazole). For cutaneous/nail candidosis, the mean age of the patients was 45 years (range, 19–82 years). C. albicans made up 59% of the isolates, C. parasilosis 20%, C. krusei 13%, C. glabrata 4%, and C. tropicalis 4%. At the MIC of 4 mg/L, 59–96% of C. albicans, 100% of C. glabrata, 83–100% of C. krusei, 89–100% of C. parasilosis, and 100% of C. tropicalis were susceptible to the drugs tested (ketoconazole, itraconazole, nystatin, amorolfine, clotrimazole, and miconazole). Conclusions C. albicans is the most common Candida species causing cutaneous/nail and vaginal candidosis in Singapore. The in vitro antifungal activities of ketoconazole, itraconazole, nystatin, amorolfine, clotrimazole, and miconazole are similar against the various Candida species. C. parasilosis in vaginal candidosis appears to be less susceptible. Here, itraconazole and amorolfine may be more effective.     

Comparative study of miconazole and clotrimazole in superficial mycosis

Two hundred cases of superficial mycosis (100 dermatophytosis, 40 candidiasis and 60 pityriasis versicolor) were studied for the comparative effect of miconazole and clotrimazole. The patients were evaluated both clinically and mycologically every 2 weeks for a period of 12 weeks. In dermatophytosis, miconazole showed accelerated response (75% cleared in 6 weeks) than clotrimazole (56%). In candidiasis, both were found to be effective (80-85%) cure though clotrimazole showed slightly earlier response (40% cure in 6 weeks) against miconazole (30% cure). In pityriasis versicolor both were, effective (miconazole 99.6% and clotrimazole 86.7%).     

Sulconazole versus clotrimazole in the treatment of dermatophytosis

Seventy-eight patients with dermatophyte infections were treated for 4 weeks with cither sulconazole nitrate 1% cream or 1% clotrimazole cream in a randomized, double-blind, parallel study. After 4 weeks of treatment dermatophytes could no longer be isolated from 92%, of clotrimazole-treated patients and 90%, of those treated with sulconazole. Both treatment groups showed 96%, eradication of the fungus 4 weeks after the end of treatment. One clotrimazole patient relapsed after giving a negative culture at the end of treatment and became positive 4 weeks later. There were no relapses for patients treated with sulconazole but one patient failed to respond clinically to 4 weeks of treatment. Three clotrimazole-treated patients relapsed clinically from week 4 to week 8. Significantly less erythema was observed in the sulconazole group compared to the clotrimazole group at week 8. A statistically significant difference in favour of sulconazole was observed also for maceration. Side-effects to clotrimazole were reported by three patients, one of whom required to be withdrawn from the study. None of the patients who received sulconazole complained of adverse effects. Sulconazole nitrate cream was shown to be a safe and effective treatement for dermatophyte infections of the skin and may offer some superiority to clotrimazole.     

Dermatophyte infections in hereditary palmo-plantar keratoderma. Frequency and therapy

The frequency of dermatophyte infections in hereditary palmo-plantar keratoderma ( HPPK ) of the Unna - Thost variety was investigated in 280 patients admitted to the Department of Dermatology, Central Hospital, Boden , during 1977-1981, and was found to be 35.0%. The distribution of fungi did not differ from that found for the total number of dermatophytes. An almost complete therapeutical resistance was found especially in Trichophyton rubrum infections, when patients were treated with micronized griseofulvin and topical econazole cream. Treatment of dermatophyte infections in HPPK with 50% propylene glycol in distilled water gave poor results but when 1% econazole nitrate was added negative cultures were found in 86.4% of the patients treated for 3 weeks.     

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.     

A clinical double-blind trial of topical haloprogin and miconazole against superficial fungal infections

A clinical double-blind trial of topical haloprogin ointment and miconazole cream was carried out against superficial fungal infections of the skin and erythrasma. The trial showed that haloprogin had the same broad range of activity as miconazole being effective against dermatophyte, pityriasis versicolor, Candida and erythrasma infections. Patient acceptability was not as good for haloprogin as it was for miconazole.     

HUMAN INFECTIONS DUE TO TRICHOPHYTON EQUINUM VAR. AUTOTROPHICUM IN VICTORIA

Two cases of human ringworm caused by the dermatophyte Trichophyton equinum var. autotrophicum are reported from victoria. This fungus has been recorded as a cause of ringworm in horses in Australia but infections in man are rare and this is the first report giving details of human infections in Australia. In one of these cases the fungus was also isolated from the patient's horse. Treatment with econazole nitrate was successful in this case.     

TREATMENT OF SUPERFICIAL MYCOSES IN THE TROPICS: WHITFIELD'S OINTMENT VERSUS CLOTRIMAZOLE

Background. In tropical primary health care, essential drugs should be safe, effective, and as inexpensive as possible. To treat the very common dermatophyte infections of the skin, one may use inexpensive Whitfield's preparations, more expensive topical imidazole derivatives, or extremely expensive oral antifungals. Because a cream base is felt to be more appropriate than an ointment in tropical conditions, we wanted to compare the effectiveness of Whitfield's cream and a topical imidazole derivative in field conditions in the tropics. Methods. A double-blind trial was performed involving 153 patients with a dermatophyte infection of the skin in Karonga District, Northern Malawi, including 25 patients who were Hiv-i-seropositive, comparing Whitfieid's cream with clotrimazole cream. Results. 75 patients were treated with Whitfield's cream and 78 with clotrimazole cream for a period of 6 weeks. Cure rates ranged from 80% to over 90% depending on the definition of cure. If positive cultures after treatment were used as criterion for treatment failure, six were found in each treatment group. One in each treatment failure group was an mv-i-seropositive patient. Conclusions. The great majority of patients in the tropics with a dermatophyte infection of the skin can be cured with a topical antimycotic preparation and do not need expensive oral therapy. This also proved to be valid for HIV-I-seropositive patients. Whitfield's cream and clotrimazole cream are both very effective. The lower cost makes Whitfield's cream the treatment of choice in dermatophyte infections of the skin in tropical primary health care.     

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.     

Clotrimazole and econazole in the treatment of vaginal candidosis. A single-blind comparison

Clotrimazole and econazole used as treatment for vaginal candidosis are both effective when given for three days. In a single-blind controlled study of 110 women followed for 14 days the efficacy of treatment with clotrimazole and econazole for three days was equal. Eighty-six per cent of the group treated with clotrimazole were mycologically clear at 14 days compared with 90% of those treated with econazole. Both treatment regimens were equally acceptable to the patients and no side effects were reported.