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At least 19 recordsLinked to original sources
PubMed1976

Mechanism of action of miconazole: labilization of rat liver lysosomes in vitro by miconazole.

Miconazole, a potent antifungal agent, labilizes rat liver lysosomes. Its labilizing effect is followed by measuring the release of lysosomal hydrolases, namely, acid phosphatase, beta-glucuronidase, and arylsulfatase A. The effect of miconazole is concentration dependent in the range of 10(-5) to 1.2 x 10(-4) M. However, at higher concentrations, miconazole inhibits enzyme release but does not inhibit enzyme activities per se. The effect of miconazole depends on the drug/lysosome ratio and is influenced by the pH of the incubation media, being minimal at alkaline pH. Membrane-active drugs such as nystatin, 2-phenethyl-alcohol, hexachlorophene, and digitonin have been compared with miconazole for their lysosome-labilizing action. The effect of miconazole on the lysosomal membrane is confirmed by a decrease in turbidity of the lysosomal suspension.

Acid Phosphatase↗
PubMed1978

Treatment of experimental murine cryptococcosis: a comparison of miconazole and amphotericin B.

Miconazole was compared with amphotericin B in the treatment of murine cryptococcosis. Both subcutaneous and intraperitoneal administration of miconazole produced serum levels higher than the minimum inhibitory concentration for the challenge strain. However, maximal tolerable doses of miconazole gave no increase in survival. When combined with amphotericin B, miconazole demonstrated neither additive nor antagonistic effects on survival. Spleen and brain counts of cryptococci were not lowered by miconazole; also, miconazole did not alter the effect of amphotericin B on reducing tissue counts. In vitro studies confirmed that the strain of Cryptococcus neoformans was quite susceptible to both miconazole and amphotericin B. However, miconazole had a delayed onset of antifungal activity. This was apparent even at miconazole levels 20 times greater than the minimum inhibitory concentration. Also, the antifungal activity of miconazole was markedly inhibited by serum. Delayed antifungal activity and serum inhibition may limit the in vivo effectiveness of miconazole in murine cryptococcosis.

Amphotericin B↗
PubMed1978

Therapeutic failures with miconazole.

A retrospective review of therapeutic failures of miconazole in three patients is presented. Miconazole, a new imidazole derivative, is a broad-spectrum antifungal agent purportedly effective topically, orally, and parenterally against a number of species of fungi. Three patients with the following culturally proven deep fungal infections were treated with miconazole: (i) destructive arthritis (Sporothrix schenckii), (ii) meningoencephalitis (Cryptococcus neoformans), and (iii) disseminated aspergillosis (Aspergillus fumigatus). All the organisms were susceptible in vitro to 1.56 mug or less of miconazole per ml using a broth dilution technique. In each patient, miconazole administered intravenously in dosages of 30 mg/kg per day failed to control or eradicate infection. Miconazole serum levels ranged from <0.5 to 4.35 mug/ml as determined by radial diffusion bioassay. Cerebrospinal fluid levels were virtually undetectable. In one patient (C. neoformans), miconazole was given intraventricularly in doses of 15 mg without response. Therapeutic failures were attributed to suboptimal body fluid levels of miconazole. The reason(s) for such low levels of activity was not clear, but may have been poor penetrance into tissues, in vitro inactivation, and/or unusually rapid excretion. Untoward reactions from miconazole included fever, chills, nausea, vomiting, and phlebitis.

Adult↗
PubMed1978

Prophylactic treatment with miconazole in patients highly predisposed to fungal infection. A placebo-controlled double-blind study.

In a placebo-controlled double-blind study the prophylactic value of oral systemic treatment with the antimycotic agent miconazole was assessed in 30 highly predisposed patients receiving intensive cytostatic chemotherapy because of haematological malignancies. Patients colonized with Candida before treatment were not freed from this micro-organism by miconazole treatment. However, only 3 out of 6 initially non-colonized miconazole-treated patients became colonized during the study, against 10 out of 10 placebo-treated patients (p = 0.036). Seven out of 15 patients in the placebo group developed clinical mycosis, against only two out of 15 in the miconazole group. The miconazole-treated patients remained clinically free of mycosis for 252 out of 264 treatment days, while the placebo-treated patients remained free of mycosis for only 263 out or 338 treatment days (p = 0.0001). The results indicate that systemic miconazole treatment protects highly predisposed patients from colonization with Candida and prevents or postpones clinically established candidosis.

Administration, Oral↗
PubMed1977

Cutaneous candidiasis: treatment with miconazole nitrate.

In a well-controlled, double-blind, randomized study, 30 patients with cutaneous candidiasis were treated with a 2% miconazole nitrate lotion or its placebo control. By the 14th day, 13 of the 15 patients [87%] treated with miconazole nitrate achieved clinical and mycologic cures. Only a single patient treated with the placebo lotion would be classified as a therapeutic cure. In a second portion of the study those patients judged to be therapeutic failures were treated with the lotion containing 2% miconazole nitrate. By combining the results of both portions of the study we find that miconazole nitrate lotion produced both a clinical and mycologic cure in all patients receiving the active lotion. The miconazole lotion formula was well tolerated by all patients and no side effects were noted. The fact that miconazole nitrate acts rapidly in relieving symptoms, is well tolerated, and is highly effective against dermatophytes, yeasts and gram-positive bacteria, makes it a welcome addition to available topical therapy of skin infections.

Candida albicans↗
PubMed1978

Miconazole therapy for fungal meningitis.

Eight patients with fungal meningitis (5 with the coccidioidal type, 2 with cryptococcal, and 1 with histoplasmosis) were treated with intravenous (IV) and intrathecal (IT) miconazole after previous therapy with amphotericin B proved unsuccessful. Miconazole was well tolerated with both IV and IT administration. The CSF concentration of miconazole one hour after an IV infusion of 800 mg was 0.1 to 0.3 microgram/ml. When 20 mg of miconazole was administered intrathecally via lumbar injection in patients with coccidioidal meningitis, 6.5, 2.4, 0.77, and 0.24 microgram/ml, respectively, was found in the CSF at the cisternal level at 12, 24, 48, and 72 hours, respectively. Miconazole is apparently an effective fungistatic drug of low toxicity and is a potentially useful agent in the treatment of systemic mycoses and fungal meningitis, in particular.

Adult↗
PubMed1979

Intraocular penetration of miconazole in rabbits.

Data from this in vivo albino rabbit study suggest that miconazole nitrate may penetrate the ocular compartments better than either natamycin or amphotericin B after intravenous, subconjunctival, or topical administration. The concentrations of miconazole in cornea and in aqueous humor after either topical or subconjunctival administration were very high, and a further threefold increase in the levels was seen if the corneal epithelium had been removed prior to drug therapy. Miconazole was found in the vitreous in some animals after subconjunctival injections of the drug. Intravenous administration produced high concentrations of miconazole in the aqueous humor, which rapidly fell over eight hours. No signs of toxicity or adverse reactions were found in these short-term experiments. Miconazole may be a useful addition in our methods of treating keratomycosis and oculomycosis.

Administration, Topical↗
PubMed1978

Evaluation of miconazole therapy in experimental disseminated candidiasis in laboratory rats.

Miconazole, a broad-spectrum antimycotic agent with some antibacterial activity, has recently become available for experimental parenteral use in the United States. Its efficacy as an anticandidal drug was tested in adult Wistar rats. A previously established infectious dose of 5 x 10(6)Candida albicans was intravenously injected into 250- to 300-g animals. This dose was fatal to 95% (20/21) of placebo-treated control animals within the 2-week postinfection observation period. Only 4% (2/53) of rats receiving intramuscular miconazole treatment died. Miconazole therapy in Candida-infected rats at a dosage of 50 mg/kg per day resulted in 85% survival, and, although 100 mg/kg per day was 100% efficacious, it was a relatively large volume to give intramuscularly to a rat. Therefore, 75 mg/kg per day was used as a therapeutic dose, and it gave favorable results in this study. Histological examination of all placebo-treated animals revealed C. albicans and a marked inflammatory response in the kidney, brain, and heart. C. albicans organisms were observed to be very prominent in these tissues by using the Gomori methenamine silver stain, and were cultured from these organs. Miconazole-treated rats that were killed after surviving the 2-week observation period had minimal histopathological changes, and the organisms present did not exhibit the same staining characteristics, nor were they isolated like those in the placebo-treated group. Miconazole appears to be an efficacious drug for parenteral therapy, as demonstrated in this reproducible model of disseminated candidiasis in laboratory rats, and more extensive experimental studies are indicated.

Animals↗
PubMed1978

Systemic miconazole treatment of a patient with chronic granulomatous mucocutaneous candidiasis.

Miconazole given intravenously and orally was evaluated in the treatment of a patient with drug-resistant, chronic, widespread horny candida lesions. Marked clinical improvement occurred after 4 weeks of the first course of treatment, in which 400 mg of miconazole per day was given intravenously. After 3 months no signs of the disease were apparent. The patient remained free of symptoms for 3 months, after which the lesions recurred and a second course of treatment, with 200 mg of miconazole per day intravenously, was started. A prompt clinical clearing was seen within 3 weeks, after which the miconazole (1 000 mg per day) was given orally. During oral administration of the drug a limited degree of recurrence of horny patches occurred. Systemic miconazole seems to be the drug of choice in the treatment of systemic chronic mucocutaneous candidiasis.

Administration, Oral↗
PubMed1977

Treatment of fungal meningitis with miconazole.

Twelve patients with fungal meningitis (ten cases were due to Coccidioides immitis, two were from Cryptococcus neoformans) were treated with brief courses of intravenous (IV) miconazole. Eleven patients, including patients with severe, chronic disease, had been treated unsuccessfully with amphotericin B. Four patients also received miconazole injected directly into the CSF. The drug was well tolerated by any route, with mild reversible side effects. After IV administration the miconazole concentration in the CSF rarely exceeded the minimal inhibitory concentration (MIC) of the infecting organism. Intra-CSF administration of 20 mg generally produced levels above the MIC for 24 hours. Five of ten patients with coccidiodial meningitis responded clinically. Of these five, four received only IV miconazole; three relapsed after therapy was stopped. Miconazole appears promising as a treatment of fungal meningitis, but trials of longer duration might prevent relapse.

Adolescent↗
PubMed1978

Vulvovaginal candidiasis treated with clotrimazole cream in seven days compared with fourteen-day treatment with miconazole cream.

Clotrimazole 1 per cent vaginal cream administered daily over a seven-day period was compared with miconazole nitrate 2 per cent vaginal cream administered daily over a 14 day period for the treatment of vulvovaginal candidiasis in a double-blind study of 65 women with clinical symptoms of this condition,, for whom treatment was randomly allocated. When efficacy of treatment was evaluated in 44 of these patients, a success rate, based on both clinical and mycologic criteria, of 75 per cent was found in the 20 patients treated with clotrimazole for seven days as compared with a 63 per cent success rate in the 24 patients treated with miconazole for 14 days. Of the 65 women enrolled in the study, two of the miconazole-treated patients experienced burning sensations, whereas the clotrimazole-treated patients experienced no adverse reactions. Thus, in this group of patients clotrimazole 1 per cent vaginal cream was shown to have a slightly, but not significantly, better efficacy than the miconazole nitrate 2 per cent vaginal cream, with no adverse reactions and in half the treatment time.

Adolescent↗
PubMed1976

Effect of culture media on the antifungal activity of miconazole and amphotericin B methyl ester.

The capacity of four culture media to obfuscate the antifungal activity of miconazole and amphotericin B methyl ester was evaluated qualitatively by examination of five isolates each of Candida albicans, Candida tropicalis, Candida parapsilosis, Torulopsis glabrata, and Cryptococcus neoformans, and quantitatively by determination of the absolute minimal inhibitory concentrations for a strain of C. albicans. Miconazole, like the predecessor imidazole (clotrimazole), was antagonized by two complex, undefined media (Sabouraud's glucose and brain-heart infusion agars) but not by either of two synthetic formulations (synthetic amino acid medium, fungal and modified yeast-nitrogen base). The antifungal activity of amphotericin B methyl ester, like that of the parent compound amphotericin B, was not materially affected by the culture medium used for testing. When added separately to synthetic amino acid medium (fungal), neither purines nor pyrimidines antagonized miconazole. Ether extraction of Sabouraud's glucose agar failed to diminish the antagonism of this medium for miconazole.

Amphotericin B↗
PubMed1975

Miconazole: a review of its antifungal activity and therapeutic efficacy.

Miconazole2, a synthetic imidazole derivative, is a new topical antifungal agent for use in the local treatment of vaginal, and skin and nail infections due to yeasts and dermatophytes. It is particularly active against Candida spp., Trichophyton spp., Epidermophyton spp., Microsporum spp. and Pityrosporon orbiculare (Malassezia furfur), but also possesses some activity against Gram-positive bacteria. In vaginal candidiasis, miconazole vaginal cream has produced higher cure rates than conventional nystatin vaginal tablets or amphotericin B vaginal cream. There have been no published comparisons with nystatin vaginal cream or foaming vaginal tablets - the nystatin dosage form preferred by some clinicians. The vaginal cream has also achieved a cure where previous nystatin or natamycin therapy had failed. Miconazole has proved equally effective in both Candida and dermatophyte infections of the skin, but as yet there have been no published comparisons with other antifungal agents. However, it has been successfully used in chronic skin infections which had not responded satisfactorily to other agents such as natamycin and pecilocin. Preliminary experience with oral and intravenous miconazole therapy in systemic candidiasis is promising. Miconazole preparations are well accepted and tolerated.

Administration, Oral↗
PubMed1978

Paracoccidioidomycosis (South American blastomycosis): treatment with miconazole.

Six patients with multisystem paracoccidioidomycosis proven by serology and culture or smear were treated with relatively brief courses of intravenous miconazole. Two had relapsed following prior therapy; 6 had active pulmonary, 4 laryngeal, 2 oropharyngeal, 2 lymphoid, and 1 abdominal disease. Paracoccidioides brasiliensis was highly susceptible to miconazole in vitro; minimal inhibitory concentration was less than or equal to 0.001 microgram/ml. Clinical examination showed a prompt and objective response in all patients, confirmed by smear or culture and X-rays; in 4/6 serological response was shown. Side effects were minor. Two patients relapsed 3--5 mo after therapy; another had a rise in antibody 6 mo after therapy and was given maintenance oral sulfa. One remains in remission 7 mo after treatment; two given oral sulfa after response to miconazole remain in remission 4--6 mo after treatment. Paracoccidioidomycosis responds well to miconazole, but longer courses may be needed to prevent relapse.

Adolescent↗
PubMed1975

The action of miconazole of the growth of Candida albicans.

The growth of Candida albicans was studied in control cultures and in the presence of miconazole or clotrimazole. Each drug prolonged the lag phase and reduced the total final population. Although miconazole, at the low concentrations used, was a less potent inhibitor than clotrimazole in the main logarithmic phase, it was more fungicidal. The antifungal activity of miconazole on C. albicans was inversely proportional to the number of cells inoculated in the media. The effects of miconazole on growth depended on the nutrients in the medium and were most pronouncedwhen it was added to cultures of C. albicans in the lag and main logarithmic phase of growth. The growth inhibitory effects of sub-fungicidal doses of micronazole (smaller than or equal to 10-6 M) on C. albicans seemed to be reversible.

Antifungal Agents↗
PubMed1976

Recurrence of vulvovaginal candidosis during pregnancy. Comparison of miconazole vs nystatin treatment.

The efficacy of miconazole and nystatin in the treatment of vulvovaginal candidosis was compared in a multicenter trial involving 94 pregnant patients. All patients had subjective complaints and were mycologically positive. Miconazole 2% vaginal cream was applied once daily for at least 10 days by 45 patients, whereas the 49 others received nystatin tablets for intravaginal application during 7 to 9 days. At the first examination following treatment, the cure rate with miconazole was 83% and with nystatin 68%. Follow-up examinations revealed a significantly lower recurrence rate in the miconazole-treated group. No important adverse experiences were noted.

Adult↗