Fluconazole and fungal infections

Diagnostic and treatment problem of ENT fungal diseases remains actual, as currently there is no tendency for decrease of weight of this pathology in the structure of ENT diseases. Particularly in recent years, the incidence of

The problem of diagnostics and treatment of ENT fungal diseases remains actual, since currently there is no tendency for the share of this pathology to decrease in the structure of ENT diseases. Particularly in recent years increased incidence of pharyngomycoses. The mucous membrane of the pharynx, including the tonsils, serves as a gateway for fungal infection. The main causative agents of oropharyngeal mucosa mycosis are different kinds of yeast-like fungi of the Candida genus. The frequency of candidiasis pharyngitis and tonsillitis has increased sharply for the last 10 years, making up 30-45% in the structure of infectious lesions of the pharynx and tonsils. The increase in the number of patients with pharyngomycoses is caused by a significant increase in the risk factors of their development among which the leading positions are occupied by iatrogenic immunodeficiency conditions resulting from massive antibiotic therapy, long-term use of glucocorticoid and immunosuppressive drugs in cancer, blood diseases, AIDS, organ transplantation, as well as in cases of severe somatic pathology, such as diabetes mellitus. This creates optimal conditions for the development of pharyngomycosis, the causative agents of which are Candida opportunistic fungi that can saprophyte on the oropharyngeal mucosa and in the environment, and under the above conditions they actively reproduce and become pathogenic.

The problem of revealing and rational treatment of pharyngomycosis becomes important not only because of its increasing spread, but also because chronic tonsillitis and pharyngitis are more severe than other inflammatory processes of the same localization and can become a primary focus of disseminated visceral mycosis, or become a cause of fungal sepsis. Despite the creation and introduction into clinical practice of a large number of local and a number of systemic antifungal drugs, the treatment of candidiasis pharyngitis and candidiasis tonsillitis is a rather complicated task. For patients with developed resistance of fungi to various antimycotic agents, selection of therapy for them seems to be a problem. This is largely due to the natural resistance of certain species of fungi of the genus Candida to the antifungal drugs used in clinical practice. Most of them have mainly fungistatic effect, which contributes to the formation of resistance to antimycotics .

As other drugs of azole group, fluconazole inhibits formation of ergosterol, the main component of the cell membrane of fungi, acting on the enzyme 14a-demethylase, which is a part of the cytochrome Р450 system. Disruption of membrane biosynthesis determines the fungistatic effect of the drug, and in higher concentrations, damage to the membrane, during peroxidation and other processes leads to cell death of the fungus (fungicidal effect). Unlike other azole preparations fluconazole possesses high specificity towards cytochrome P450-dependent enzymes of the fungus.

The aim of this work was to evaluate the efficiency of a new drug from the azoles group fluconazole in the treatment of oropharyngeal candidiasis diseases.

Fluconazole, a member of the triazole antifungal class, is a potent selective inhibitor of sterol synthesis in fungal cells. For ergosterol synthesis inhibitors to take effect, conditions must be provided for their penetration into the fungal cell, accumulation in sufficient concentration, movement to microsomes on which the target enzyme is located, and binding to this enzyme. Fluconazole, highly effective in opportunistic mycoses. All patients underwent general clinical and mycological investigations. Diagnosis of the disease included analysis of the results of the following studies:

• Study of the objective clinical picture of the disease in the lesion nidus, t. е. At the site of the fungus, including a description of all clinical manifestations, as well as the type and nature of the pathological secretion.
• Study of the features of the fungus in the pathological material by microscopic examination of native and stained preparations.
• Identification of cultural features of the fungus, involving the description of the initial colonies of fungi obtained by inoculation of pathological material on various nutrient media.
• Identification of fungus species using a number of media and studying both microscopic picture of fungus, peculiarities of its development, and its biological activity.

The clinical course of pharyngomycosis in such patients was characterized by a number of peculiarities. In chronic fungal tonsillitis the main complaints of patients are pain in the throat, foreign body sensations, tingling, itching in the throat, burning. Objectively: hyperemia, swelling of the sinuses (both anterior and posterior) without visible infiltration, which distinguishes the fungal process from the bacterial one; the tonsils themselves are hyperemic, lacunes are dilated, the mucous membrane is partially eroded. One of the characteristic objective signs of mycotic disease of tonsils is the presence of plaques both on the tonsils and on the sinuses; sometimes the plaques extend to other parts of the oropharynx. Plaques are formed not only in the period of exacerbation, but also in the absence of exacerbation of chronic tonsillitis. Most often, they are small, dotty or island-like, located near the tonsil lacunae, whitish in color, of a curd-like nature, soft, and easily removable. Frequent exacerbations (from 2 to 10 times a year) are characteristic of chronic tonsillitis.

Fungal chronic pharyngitis differs from mycosis of tonsils mainly by localization of the pathological process. Unequal hyperemia and infiltration of the mucous membrane of the posterior wall of the oropharynx is a characteristic clinical sign of a chronic pharyngitis of fungal etiology. Against the background of subatrophy there is an enlargement of lateral rollers and a single, rounded infiltrative inflammatory process in the center. The presence of small plaques is also a sign of mycotic pharyngitis. The nature of inflammation is chronic, accompanied by frequent exacerbations.

Mycological diagnostics has revealed causative agents of pharyngomycosis in 44 patients. In fungal pharyngitis – Candida albicans (22), Candida krusei (2), Candida tropicalis (3), Candida guilliermondi (1). In fungal chronic tonsillitis – Candida albicans (10), Candida stellatoidea (3), Candida intermedia (2), Candida pseudotropicalis (1). All patients received fluconazole orally in a dose of 50 mg

1 time per day. In chronic fungal pharyngitis the duration of treatment was 14 days, in chronic fungal tonsillitis – 20 days.

Control clinical and mycological examination was performed after 10 days, after 1 month and after 2 months after taking the drug.

Thus, as a result of the treatment of 44 patients with pharyngomycosis with fluconazole the cure was achieved in 29 (65%) patients (confirmed by mycological and clinical tests), improvement in 14 (33%) patients, no effect was observed in 1 (2%) patient. When analyzing the results of the study separately by nosological groups (form of the disease), it was found that the cure of the fungal process in candida pharyngitis was achieved in 71% of patients, and in candida tonsillitis – in 56%. This is understandable, since fungal chronic tonsillitis is a more severe disease than chronic fungal pharyngitis, and its therapy is more difficult and rarely effective enough with other antimycotic agents. A clear dependence of treatment efficacy on the duration of the disease has been established. In all the cases when the therapy was inconclusive (1) or complete cure was not achieved, the duration of the fungal process was from 7 to 15 years. The study did not reveal the relationship between the effectiveness of treatment and the type of fungus – the causative agent of the disease. Fluconazole appears to have a fungicidal effect on all Candida species that were identified as causative agents of pharyngomycosis in this study.

Good tolerability of the drug should be noted. No adverse reactions or manifestations of allergy have been reported while taking fluconazole.

On the basis of the above it can be concluded that on the whole the positive effect of fluconazole treatment was achieved in 97% of pharyngomycosis patients.

Twenty seven patients (15 females and 12 males aged 17 to 58 years) with duration of the disease from 3 months to 8 years participated in the comparative clinical trial of Diflucan (fluconazole). The causative agents were Candida albicans (21), Candida stellatoidea (4), Candida krusei (2). All patients underwent general clinical and mycological examinations similar to those performed during the examination of patients on fluconazole therapy. Diflucan was treated in the same dosages as fluconazole, i.e. е. 50 mg once daily. Duration of treatment was: in chronic fungal pharyngitis – 14 days, in chronic fungal tonsillitis – 20 days.

As a result of treatment of 27 patients with pharyngomycosis with Diflucan, a cure, confirmed by mycological and clinical studies, was achieved in 18 patients, an improvement – in 8 patients, and no effect – in one patient. Thus, the cure was achieved in 66% of cases, and on the whole, a positive effect of diflucan treatment was obtained in 96% of the patients suffering from pharyngomycosis. Tolerability of the drug was evaluated as good. Only three patients experienced abdominal complaints in the form of nausea, dyspepsia, diarrhea.

Thus, in a comparative analysis of the effectiveness of therapy with drugs of the azole class: fluconazole, similar results were obtained. Tolerability of fluconazole appeared to be higher, as no adverse reactions were observed during its treatment, which significantly improves patients’ adherence to treatment with this drug.

Thus, high efficacy of fluconazole in the treatment of patients with pharyngomycosis (97% positive effect), its good tolerability and convenient use (once a day) allow to consider this drug as the most promising in the treatment of chronic tonsillitis and chronic pharyngitis of candidiasis etiology.