Persistence of miconazole in vaginal secretions after single applications. Implications for the treatment of vaginal candidosis.

In vaginal secretions from 16 healthy women aged between 20 and 27 years miconazole persisted in biodetectable concentrations for at least 48 hours after insertion of a single miconazole vaginal pessary. This finding casts doubt on cure rates in vaginal candidosis determined soon after the end of treatment and suggests that current treatment courses with imidazole antifungal agents may be longer than their nominal three or five days.     

Recurrent vaginal candidosis: prospective study of effectiveness of maintenance miconazole treatment.

In a prospective study, 100 women with recurrent vaginal candidosis were treated with miconazole, using two 100 mg vaginal pessaries a day for one week, then one pessary twice a week for three months followed by one pessary a week for a further three months. Fifty four women elected to continue using one pessary a week for longer than six months. Symptomatic vaginal candidosis did not occur in any patient during regular maintenance treatment. Of the 46 women who discontinued treatment before six months, however, 22 had a recurrence. Maintenance prophylactic treatment with miconazole pessaries appears to be an acceptable and effective method of preventing recurrent episodes of vaginal candidosis.     

Miconazole as adjuvant therapy for oral lichen planus: a double-blind randomized controlled trial

BACKGROUND: Topical steroids are the first choice for the treatment of oral lichen planus (OLP). Antifungal drugs are often employed together with them, to prevent secondary oral candidosis, although it has been suggested anecdotally that they can also be beneficial for OLP itself. OBJECTIVES: To compare the effect of clobetasol propionate with and without a topical antifungal drug (miconazole) on the symptoms and extension of OLP. METHODS: A randomized, parallel, double-blind trial was conducted at the Unit of Oral Medicine and Pathology of the University of Milan. Thirty-five outpatients with histologically proven OLP were randomly assigned to receive either clobetasol propionate and miconazole, or clobetasol propionate and placebo for 6 weeks. Primary outcomes included symptoms and extension of lesions; adverse effects were also recorded. RESULTS: All the patients who concluded the study (30 of 35) showed clinical and subjective improvement within 3 weeks. The addition of miconazole did not affect in a significant way the signs and symptoms of OLP. No cases of clinical candidosis were seen in the patients taking miconazole, while one-third (five of 15) of the placebo group were affected. CONCLUSIONS: Although effective in preventing iatrogenic candidosis, the addition of miconazole to topical steroid treatment does not improve the efficacy of the therapy.     

Single blind comparison of ketoconazole 200 mg oral tablets and clotrimazole 100 mg vaginal tablets and 1% cream in treating acute vaginal candidosis.

A single blind study of 103 women with vaginal candidosis was undertaken to compare treatment with conventional topical clotrimazole and oral ketoconazole. Both treatment regimens were equally effective in terms of clinical symptoms, negative results on culture for Candida albicans, and relapse rates. As treatment for vaginal candidosis takes several days, patient compliance is important and the success of a treatment regimen may depend on its acceptability to patients. Those in this study who had previously been treated for vaginal candidosis were asked to compare their current and previous treatments. Significantly more (p less than 0.001) of those treated with ketoconazole than those treated with clotrimazole found it more acceptable than previous treatment. This indicated a strong preference for oral treatment, and oral antifungal agents may be the treatment of choice for vaginal candidosis in the future.     

Contact dermatitis from topical imidazole antifungals: 15 new cases

Contact allergy from topical imidazole antifungals is seldom reported. 15 such cases, over a 12-year period, are reported here. Results are discussed particularly with regard to imidazole cross-reactions and to sensitization to topicals combining miconazole and hydrocortisone.     

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.     

Comparison of miconazole-coated tampons with clotrimazole vaginal tablets in the treatment of vaginal candidosis.

The effectiveness and acceptability of miconazole-coated tampons were compared with those clotrimazole vaginal tablets in the treatment of vaginal candidosis in 100 women. Both treatments were highly effective in reducing the signs and symptoms of infection; 95% of the group treated with miconazole had negative culture results for Candida species immediately after treatment compared with 86% of those treated with clotrimazole. A 17.6% recurrence rate of positive culture results was found four weeks later in the miconazole-treated group compared with that of 30% in the clotrimazole-treated group. The miconazole tampons were highly acceptable to patients. Vaginal pH values did not differ significantly between those patients with candidosis and those treated and cured. Corynebacterium vaginale (Gardnerella vaginalis) vaginitis and nonspecific genital infection were common complicating factors during follow up.     

A New Treatment for Cutaneous Candidiasis: Sulconazole Nitrate Cream 1%

Sulconazole nitrate cream 1%, a new topical imidazole compound with a broad antifungal activity, was compared to its vehicle and to miconazole nitrate cream 2% in two double-blind parallel studies involving 96 patients with cutaneous candidiasis. Once daily application of sulconazole was as effective as twice daily application of miconazole and produced KOH and culture cures in 100% and 88% of patients, respectively. No systemic adverse reactions were reported. One vehicle-treated patient developed itching; six sulconazole- and three miconazole-treated patients developed erythema and/or pruritus, which was mild and transient. Sulconazole used bid was significantly superior to its vehicle and produced KOH and culture cures in 100% of patients.     

Oral Antifungal-Exacerbated Inflammatory Flare-Up Reactions of Dermatomycosis

Inflammatory flare-up reactions of some dermatomycoses, particularly those caused by zoophilic fungi, are typical and potentially severe adverse effects following the intake of some oral antifungals. However, this condition has not previously been reported with the most frequently used antifungals in dermatology, namely fluconazole, itraconazole, and terbinafine. In this report, we describe five patients, observed over a 10-year period, who presented with inflammatory exacerbations following oral antifungal therapy for dermatomycoses. We also review the literature on inflammatory reactions exacerbated by oral antifungal agents. Details of the patients' age, sex, occupation, and atopic background; the site of the lesion, its clinical and histologic features, and any systemic signs; the identity of the fungal pathogen; the antifungal agent taken by the patient; the time between drug intake and occurrence of the flare-up; the approach to management; and the outcome were documented for each patient. A PubMed literature search was also conducted, focusing on inflammatory exacerbations induced by griseofulvin, ketoconazole, itraconazole, fluconazole, and terbinafine. The patients were four farmers and one veterinarian (all male). All primary lesions were inflammatory dermatophytoses, including one kerion. Inflammatory exacerbation of the skin lesions started 12-24 hours after the intake of oral antifungals. Mild systemic changes, including slight fever and malaise, occurred in two cases. Itraconazole 400 mg/day was implicated as the causative agent in four cases and terbinafine 250 mg/day in one case. Mycologic cultures grew Trichophytonverrucosum in four cases. Antifungal treatment was discontinued in all patients. Oral and topical corticosteroids were administered to the two patients with systemic changes; the other three patients were treated with topical corticosteroids only. Two days after the onset of corticosteroids, lower doses of itraconazole (100 mg/day) and terbinafine (125 mg/day) were reintroduced. All lesions healed after 4-5 weeks. The PubMed search did not identify any articles that described inflammatory exacerbations of dermatomycoses induced by oral antifungals. Inflammatory flare-up of dermatomycoses is a rare but potentially severe cutaneous complication of oral antifungal use. Occupational contact with animals, inflammatory dermatomycoses, and zoophilic fungi represent common features in these patients. Although evidence-based data are not available, clinical experience shows that, in addition to antifungal therapy, topical and/or systemic corticosteroids are helpful to reduce the inflammatory reactions. The cases described in this article represent the first published report of oral antifungal-exacerbated inflammatory flare-up reactions of dermatomycosis in patients taking itraconazole or terbinafine.     

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.     

New topical agents for dermatophytosis.

Several new synthetic antifungal agents have recently become available for topical use. Reported experiences with haloprogin, miconazole and clotrimazole are reviewed. Topical preparations of these agents are nonirritating and effective in the treatment of superficial fungus infections. They are effective in the management of tinea versicolor and cutaneous candidiasis as well as dermatophytosis.     

硝酸舍他康唑栓剂体内药效学实验研究

目的评估硝酸舍他康唑栓剂治疗大鼠念珠菌性阴道炎模型的疗效。方法取SD大鼠建立念珠菌性阴道炎模型,随机分成治疗组(4个剂量)、基质对照、阳性对照、阴性对照和空白对照共8组,硝酸舍他康唑栓剂和对照药分别每天给药1次,共治疗7天。分别于疗程结束时、停药1周后、2周后作真菌培养以判定疗效。结果硝酸舍他康唑栓剂对白念珠菌和热带念珠菌引起SD大鼠念珠菌性阴道炎的治愈率为100%(5/5),停药2周后仍保持满意的治疗效果。结论硝酸舍他康唑栓剂对念珠菌性阴道炎有较好的疗效。     

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.     

Six Novel Antimycotics

We have reviewed six new antimycotic agents which have potential applications for human cutaneous and mucosal diseases. Information on these six drugs was obtained via an English language search of PubMed through the US National Library of Medicine. The antimycotic agents reviewed include rilopirox, lanoconazole, NND-502, butenafine, eberconazole and voriconazole. Rilopirox is a synthetic pyridone derivative, related to ciclopirox, with a fungicidal action. Rilopirox is a hydrophobic, topical agent with potential application in mucosal candida infections, tinea versicolor and seborrheic dermatitis. Lanoconazole, an imidazole, is a topical agent with potential application in tinea infections and cutaneous candidiasis. The drug has been available for clinical use in Japan since 1994 and once-daily application to affected areas is recommended. In addition to its antifungal effect, animal data suggest that application of lanoconazole 0.5 or 1% cream is associated with accelerated wound healing. NND-502, a stereoselective analog of lanoconazole, is a topical agent with potential application in tinea pedis infection. NND-502 appears to be more effective in inhibiting ergosterol biosynthesis than lanoconazole or bifonazole and clinical trials comparing these agents are awaited. Butenafine is the first member of a new class of antifungals, the benzylamine derivatives, and has been approved for topical use in Japan (since 1992) and the US. Butenafine has a potent fungicidal action and the drug has been shown to be effective in multiple clinical trials in patients with tinea pedis, tinea corporis and tinea cruris. Butenafine has also been reported to exert an anti-inflammatory action after topical application and this may offer potential benefit over other topical antifungal agents. Eberconazole, an imidazole derivative, is a topical antifungal agent that has been shown to be effective in clinical trials in patients with tinea infections. Preliminary data indicate that the eberconazole is effective against some triazole-resistant yeasts such as Candida krusei and Candida glabrata. Voriconazole is an azole antifungal derivative of fluconazole. The drug is available in both oral and parenteral formulations. Oral voriconazole 200mg twice daily has been effective in treating oropharyngeal candidiasis and apergillosis in immunocompromised patients. After 12 weeks' treatment, a similar dosage of the drug elicited a positive response in 69% of nonimmunocompromised patients with invasive aspergillosis.     

Recurrent genital candidosis in women and the effect of intermittent prophylactic treatment

A study of clotrimazole for the treatment of recurrent genital candidosis unexpectedly showed that symptoms and infection can be dissociated. The aim of the study was to see if intermittent antifungal treatment would reduce symptoms in women constantly distressed by recurrent genital candidosis. Forty women seriously affected by the condition were initially given oral and local antifungal treatment. When the patients were symptom-free and the vagina was free of yeasts, they were entered into a double-blind clinical trial and were treated prophylactically for four months with either intermittent clotrimazole pessaries and cream or a placebo. The prophylactic treatment kept symptoms below a critical level but did not affect the return of the yeasts to the vagina. This dissociation between symptoms and vaginal yeasts was unexpected. Rectal yeast carriage was unaffected by prophylactic vaginal treatment. Male contacts and patients both showed a high incidence of non-specific genital infection. This association has seldom been reported. A few patients cultured yeasts from their homes but this environment was not considered a major source of reinfection. The vaginal pH did not appear to be altered by the presence of yeasts. The results of the study suggested that symptoms in women with recurrent genital candidosis were not caused by yeasts alone, and possibly the reason for recurrences might lie not in constant reinfection by yeasts, but in failure to recognise and remove a primary underlying factor, perhaps infection with other sexually transmitted agents. The question of a synergistic action between yeasts and other organisms is discussed.     

A study of candidosis: the role of fomites.

This study investigates treatment failure and recurrences of vulvo-vaginal candidosis. It reviews the factors possibly associated with both. Patients attending a department of genitourinary medicine with recurrent candidosis (N = 186) were entered in the trial. The patients were investigated for evidence of candidosis from vagina, rectal wall and buccal mucosa and were given antifungal therapy. Prevention and reinfection via fomites was studied by means of a single blind parallel study comparing the effect of soaking undergarments in the amphoteric biocide Tego 103G with the effect of a placebo soak. General and possible contributory factors influencing treatment and failure and recurrences were considered. The success rate of miconazole therapy was typical of any imidazole therapy: 85.4%. There was no evidence that modern oral contraceptives played a role in candidosis. Oral nystan reduced the rectal wall carriage from 39.2% to 23.2%. Oral yeast carriage rate in women was 37.6%. The recurrence rate over a six month period was 47.4%. The laboratory results of Tego soaking reduced the yeast carriage on panties from 85.2% to 23.4%. However, no evidence was found in the trial results that panties were a significant source of reinfection.     

A new drug combination for the topical treatment of acne. Miconazole 2% + benzoyl peroxide 5% versus benzoyl peroxide 5%--a double-blind study

A double-blind, controlled clinical trial with 60 patients was employed in order to study the relative merits of two treatment schedules in acne vulgaris. One therapy comprised the topical application of a cream containing a combination of miconazole 2% and benzoylperoxide 5% (Acnidazil, Janssen) twice a day. In the other therapy, we applied a cream containing only benzoylperoxide 5%. Both groups of patients showed large and statistically significant reduction in the number of comedones, papules, and pustules during 12 weeks of therapy. Acnidazil, however, was found to have definitely better therapeutical results than benzoylperoxide alone: The lesions improved significantly faster, tolerance was better, and the patients overall evaluation clearly favored Acnidazil. 86,2% of the patients treated with Acnidazil rated the results good to very good, in contrast to 63% of the patients treated with benzoylperoxide only (p = 0.037).     

Antiproliferative effects on keratinocytes of a range of clinically used drugs with calmodulin antagonist activity

Thirty-two drugs, including some in use for a variety of clinical disorders, were examined for their ability to inhibit calmodulin activity in vitro . From these. 10 drugs were selected for their inhibition of calmodulin activity and examined for their ability to inhibit proliferation of rapidly dividing human keratinocytes. A significant correlation between antiproliferative activity and calmodulin antagonist potency was found. Of these drugs there were several, including miconazole. dequalininm chloride, bromocriptine and tamoxifen, whose use is well established and well documented. The potential use of these drugs (and others identified in this way) as antipsoriatic agents is discussed.     

Genital candidosis*

Vaginal thrush is a condition that has been known to medicine for well over a century. Over the years it has received considerable clinical and laboratory attention, Candida albicans, by far the predominant cause of thrush, has been scrutinized in fine detail by biochemists, microbiologists and immunologists. A plethora of antifungals formulated for intravaginal use has been made available to combat the infection. Yet vaginal candidosis remains one of the most common gynaecological complaints in Europe and North America. Its diagnosis is usually simple, but its treatment can be extremely difficult. There is still doubt as to the major epidemiological and pathological factors involved in the aetiology of the infection, so the reasons for failure by some patients to respond to treatment are uncertain. Meanwhile, candidosis of the penis, which appears to have about one-tenth the prevalence of vaginal candidosis, has attracted very little research interest at all. This article will describe aspects of genital candidosis that have been the subject of research in recent years.