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PubMed1983

Antifungal agents used in systemic mycoses. Activity and therapeutic use.

The development of the polyene antibiotic, amphotericin B, provided for the first time a drug which was clinically effective in many serious mycotic diseases. Unfortunately, it requires parenteral administration and is often toxic, factors which limit the total cumulative dose which can be given. Efforts to utilise combinations of amphotericin B with other agents were best realised with amphotericin B/flucytosine in cryptococcal meningitis, and to a lesser degree in systemic candidiasis. More recently, the introduction of new imidazoles has extended the range of applications of these drugs to fungal diseases. Two members of this group, miconazole and ketoconazole, are promising agents. Miconazole is a parenterally administered agent for patients acutely ill with candidiasis and other mycotic infections. It may be the drug of choice for Petriellidium boydii infections and it is an attractive alternative to amphotericin B for intrathecal administration to patients with fungal meningitis. Ketoconazole offers much less toxicity, the advantage of oral administration, and the possibility of indefinitely prolonged therapy. However, it does not attain high concentrations in either the urine or cerebrospinal fluid. With the imidazoles, we have entered a new era of antifungal therapy which may produce even better antifungal agents than those currently available.

Amphotericin B↗
PubMed1986

Tioconazole. A review of its antimicrobial activity and therapeutic use in superficial mycoses.

Tioconazole is a substituted imidazole antimicrobial agent structurally related to other drugs in this group. It has been shown to have a broad spectrum of activity in vitro against dermatophytes and yeasts, as well as against some chlamydia, trichomonads and Gram-positive bacteria. Both open and controlled clinical trials have clearly demonstrated the efficacy and safety of topical preparations of tioconazole for treating superficial dermatophyte or yeast infections of the skin and vaginal candidiasis. In comparative studies it was at least as effective as alternative imidazole antifungal drugs, and in a few trials significantly greater efficacy has been reported for tioconazole, compared with clotrimazole, miconazole, econazole and systemic ketoconazole. Preliminary studies in other clinical areas suggest tioconazole may be useful for treating onychomycosis (in a special nail formulation), napkin-rash due to Candida albicans, impetigo, and vaginal trichomoniasis, although comparative studies are needed in each of these settings to clearly assess its relative place in therapy. Thus, tioconazole is an effective and well tolerated treatment for vaginal candidiasis and superficial fungal infections of the skin.

Administration, Topical↗
PubMed1989

Itraconazole. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in superficial and systemic mycoses.

Itraconazole is an orally active triazole antifungal drug which has demonstrated a broad spectrum of activity and a favourable pharmacokinetic profile. It is a potent inhibitor of most human fungal pathogens including Aspergillus sp. In non-comparative clinical trials itraconazole was shown to be extremely effective in a wide range of superficial and more serious 'deep' fungal infections when administered once or twice daily. Generally, greater than 80% of patients with superficial dermatophyte or yeast infections are cured by itraconazole. Similarly, good to excellent response rates (clinical cure or marked improvement) are achieved in paracoccidioidomycosis, histoplasmosis, sporotrichosis, blastomycosis, systemic candidiasis, coccidioidomycosis, chromomycosis, aspergillosis and cryptococcosis. Understandably, given the rare nature of some of these diseases, clinical experience is relatively limited and further evaluation, preferably controlled trials with amphotericin B and ketoconazole, would help clarify the ultimate role itraconazole will have in their management. Preliminary findings also indicate that itraconazole may hold promise for the prophylaxis of opportunistic fungal infections in patients at risk, for example women with chronic recurrent vaginal candidiasis, immunodeficient patients with chronic mucocutaneous candidiasis, AIDS patients and patients receiving immunosuppressant drugs. In studies to date itraconazole has been very well tolerated. Transient changes in indices of liver function occurred in 1 to 2% of patients; however, symptomatic liver dysfunction (as occurs infrequently with ketoconazole) has not been reported. Wider clinical experience is needed to permit clear conclusions as to whether liver dysfunction can result from itraconazole administration. Thus, while several aspects of the drug's profile require further investigation, itraconazole is a promising new oral treatment of fungal disease. The extent to which itraconazole will be employed in preference to ketoconazole will be clarified by wider clinical experience.

Animals↗
PubMed1989

Bifonazole. A review of its antimicrobial activity and therapeutic use in superficial mycoses.

Bifonazole is a substituted imidazole antifungal agent structurally related to other drugs in this group. It possesses a broad spectrum of activity in vitro against dermatophytes, moulds, yeasts, dimorphic fungi and some Gram-positive bacteria. Both non-comparative and comparative clinical trials have clearly demonstrated the efficacy and safety of various formulations of bifonazole 1% (cream, gel, solution and powder) applied once daily in the treatment of superficial fungal infections of the skin such as dermatophytoses, cutaneous candidiasis and pityriasis versicolor. In comparative studies bifonazole was significantly superior to placebo and at least as effective as alternative imidazole antifungal drugs including clotrimazole, econazole, miconazole, oxiconazole and sulconazole. Preliminary studies in other superficial skin and nail infections/dermatoses suggest that bifonazole may be useful for treating onychomycoses (in a combination cream; bifonazole 1% plus urea 40%), otomycoses, erythrasma, sebopsoriasis, seborrhoeic dermatitis and rosacea. However, controlled trials are needed in each of these clinical settings to assess accurately its relative place in therapy. Thus, bifonazole is an effective and well-tolerated treatment for superficial fungal infections of the skin. Compared with the majority of topical antifungal drugs, which need to be applied at least twice daily, bifonazole offers the convenience of once daily administration, which may improve patient compliance.

Antifungal Agents↗
PubMed1995

Fluconazole. An update of its pharmacodynamic and pharmacokinetic properties and therapeutic use in major superficial and systemic mycoses in immunocompromised patients.

Fluconazole is a triazole antifungal agent which is now an established part of therapy in patients with immune deficiencies. It is effective against oropharyngeal/oesophageal candidiasis (candidosis) when used orally once daily either as treatment or secondary prophylaxis in patients with AIDS or as treatment or primary prophylaxis in neutropenia associated with cancer therapy. Fluconazole also resolves symptoms in up to 60% of patients with cryptococcal meningitis and AIDS. However, in this infection its efficacy as treatment relative to that of amphotericin B is equivocal, and its major role is as the drug of choice for maintenance therapy following amphotericin B induction. In this regard, fluconazole has been proven superior to amphotericin B and to itraconazole 200 mg/day. Comparisons with other drugs used for the treatment of mucosal candidiasis in patients with AIDS show fluconazole to be superior to nystatin, similar to itraconazole and at least as effective as clotrimazole and ketoconazole; it was more so than the latter azole in 1 study. In patients undergoing chemotherapy or bone marrow transplantation, fluconazole as primary prophylaxis has produced greater clinical benefit than a clotrimazole regimen. The incidence of adverse events appears to be somewhat higher in patients with AIDS compared with HIV-negative cohorts, but the qualitative pattern of events is similar. The most frequent events are gastrointestinal complaints, headache and skin rash: rare exfoliative skin reactions and isolated instances of clinically overt hepatic dysfunction have occurred in patients with AIDS. Issues yet to be clarified include: the use of fluconazole in children with AIDS, in whom results have been promising; its efficacy against other fungal infections encountered in immunocompromised patients; whether the drug influences mortality, as has been suggested by one placebo-controlled trial in patients undergoing bone marrow transplant; and the appropriateness of its potential for use as primary prophylaxis against cryptococcal meningitis in patients with AIDS, where it shows efficacy but there is concern over increasing risk of development of secondary resistance. Notwithstanding these undefined aspects of its clinical profile, fluconazole is now confirmed as an important antifungal drug in the management of fungal infections in patients with immune deficiencies. In patients with AIDS it is the present drug of choice as maintenance therapy against cryptococcal meningitis and is a preferred agent for secondary prophylaxis against candidal infections; it is also a favoured agent for primary prophylaxis in patients at risk because of neutropenia associated with chemotherapy or bone marrow transplantation .

AIDS-Related Opportunistic Infections↗
PubMed1986

Host-parasite relationship in opportunistic mycoses.

Aspergillosis and mucormycosis are opportunistic fungal infections that share several unique features. The etiologic agents of aspergillosis and mucormycosis are ubiquitous in the environment, but are opportunistic organisms and usually infect only patients predisposed by some underlying disease or treatment. These infections are typically characterized by hyphal tissue invasion and a predilection of the organism for blood vessel invasion with hemorrhage, necrosis, and infarction. Also, these organisms are not dimorphic, like the true pathogenic dimorphic fungi, as they grow both in the environment and within the host in hyphal forms. However, the host must contend with several forms to successfully eliminate them. Each form displays different antigenic and surface features and elicits different host responses. Finally, if germination and hyphal growth occur, the host must compete with a rapidly growing organism that is too large to be ingested by a single cell and so must be handled by extracellular defense mechanisms.

Aspergillosis↗
PubMed2002

[Serodiagnosis for deep-seated mycoses].

Early diagnosis and treatment for an immunocompromised patient with a deep-seated mycosis are very important for the prognosis of the patient. Several methods of serodiagnosis for deep-seated mycosis have been developed and are clinically available. Detection of (1,3)-beta-D-glucan from serum samples of a patient can be evaluated with high sensitivity and specificity. Antigens detection test for fungi is another useful method for this serodiagnosis. A novel sandwich ELISA to detect galactomannan has higher sensitivity than the latex agglutination test. The cryptococcus capsular antigen detection technique is also very useful for patients with cryptococcosis. Thus, serodiagnosis for deep-seated mycosis appears to be a useful tool for treatment of immunocompromised patients.

Antigens, Fungal↗
PubMed2005

Mycoses in Thailand: current concerns.

Scytalidium dimidiatum is the leading cause of fungal foot diseases in Thailand, in contrast to similar studies in which dermatophytes have been identified as the predominant pathogens. By contrast, the prevalence of Candida albicans in our study was only 2.6 approximately 3.0%. Scytalidium fungal foot infection is clinically indistinguishable from that caused by dermatophytes and should be included as a possible cause of treatment failure in tinea pedis and onychomycosis. Without proper culture identification, clinically diagnosed patients would be treated with a standard antifungal regimen leading to minimal response and be interpreted as drug resistant cases resulting in switching of drugs and more aggressive management procedures. Tinea capitis is another health problem in young children. However, for Microsporum canis and some ectothrix organisms, the effectiveness of treatment may be less than endothrix infection. Griseofulvin is still the mainstay antifungal although itraconazole and terbinafine are as effective. Pulse regimen may be another option with advantages of increased compliance and convenience. Two pulses of terbinafine may be sufficient for treating most cases of Microsporum infection, although additional treatment may be needed if clinical improvement is not evident at week 8 after initiating therapy. Chromoblastomycosis is another subcutaneous infection that requires long treatment duration with costly antifungal drugs. The most common pathogen in Thailand is Fonsecaea pedrosoi. Preliminary study of pulse itraconazole 400 mg/d 1 week monthly for 9-12 consecutive months showed promising results. The prevalence of Penicillium marneffei infection is alarming in HIV infected patients living in endemic areas. Diagnosis relies on direct examination of the specimens and confirmation by culture. Treatment regimens include systemic amphotericin B or itraconazole followed by long-term prophylaxis. Treatment outcome depends on the immune status of the patient.

Chromoblastomycosis↗