Fluconazole and candidiasis: current views on the treatment of urogenital candidiasis

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Fluconazole and candidiasis infection of the urinary tract

Urogenital candidiasis — is a fungal disease of the mucous membranes and skin of the urogenital organs, caused by yeast-like fungi of the genus Candida.

Currently, more than 170 biological species of yeast-like fungi have been described, of which the causative agents of urogenital candidiasis are: C. albicans — 80% (abroad — в 45–70%), C. glabrata — в 15–30%, C. tropicalis, C. krusei, C. Parapsilosis — в 4–7% of cases.

The disease affects both men and women, but is more common in women of reproductive age. By prevalence, candidiasis vulvovaginitis ranks second among all vulvovaginal infections. Peak incidence occurs in 20–45 years.

Sexual transmission occurs in 30–40% of cases. More often (60–70%) the disease is caused by endogenous infection. During pregnancy the disease incidence increases by 10–20%, the risk of transmission to the newborn during childbirth is about 70–85%.

Risk factors usually include pregnancy, use of hormonal contraception and hormone replacement therapy (especially with first-generation hormones), long-term and unsystematic use of antibiotics, immunosuppressants, cytostatics and some other drugs. However, it should be noted that antibiotics act as a risk factor only against the background of existing candida carriage and their effect is short-lived. Carbohydrate metabolism disorders due to diabetes mellitus, contribute to the persistent course of urogenital candidiasis with frequent relapses, which are difficult to treat.

Immunodeficiency conditions, systemic diseases leading to immunodeficiency, also provoke the occurrence and recurrence of urogenital candidiasis. Candida infection is particularly severe in HIV-infected patients. Generalized Candida infections are not uncommon in the terminal stage of AIDS.

The main pathogenetic factors traditionally include an imbalance of the vaginal microflora, an increase in the concentration of estrogen and progestins in the tissues, a violation of the local immunity of the genital tract.

Vulvovaginal candidiasis — is the most commonly used name of the disease, because its main clinical manifestations are vulvovaginitis and vaginitis. However, according to localization, candida cervicitis, colpitis, urethritis, bartholinitis are also distinguished. A distinction is made according to the course of the disease:

  • Acute (fresh, sporadic) candidiasis (lasts no longer than 2 months);
  • Chronic, including: a) recurrent (at least 4 episodes per year); b) persistent (symptoms persist permanently, with some reduction after treatment).

Acute genital candidiasis is characterized by a pronounced inflammatory picture. The main complaints and symptoms of candidiasis vulvovaginitis — Itching and burning, constant or intensifying in the afternoon, in the evening, at night, after a long walk, and in patients with atopic predisposition — Under the influence of many different factors. In the vulva and labia area, itching is usually intense, accompanied by scratching. Severe, constant itching often leads to insomnia, neurosis. Itching, burning sensation, pain, especially in the area of the lesions, obstructs urination and can lead to urinary retention. Pain and burning sensation in the vagina increase during coitus and lead to a fear of intercourse and sexual frustration (dyspareunia).

The following symptom — Leukorrhea. The urine is not abundant, white, thick (creamy) or flaky, curd-like, filmy, and has a subtle, sour odor. Rarely, watery, with crusty-crusty spots. May be absent completely.

When the surrounding skin is affected, hyperemia, maceration of the skin, individual pustular elements, itching in the anus area are noted.

Candidiasis often relapses in patients with a predisposition, i.e. е. Recurrence of the disease after complete subsidence of clinical manifestations and restoration of impaired mucosal functions in the course of treatment is observed. If such relapses occur at least 4 times a year, the disease is classified as chronic recurrent vulvovaginal candidiasis. Treatment tactics in this case are different from those in sporadic episodes.

Another form of the course of a chronic infection — persistent vulvovaginal candidiasis, in which clinical symptoms persist permanently and only slightly subside after treatment. Relapses should be distinguished from exacerbations, which do not develop after the disease, but against a background of continuing clinical symptomatology. Of course, and the approach to treatment in this case is somewhat different than in other forms.

If previously the chronic and recurrent disease was explained by reinfection (either endo- or exogenous), nowadays the cause of these phenomena is considered to be a macroorganism condition, since the same strain of fungus is constantly released.

In the foreign literature, we often use the terms «complicated» и «secondary» vulvovaginal candidiasis. Complicated refers to both chronic forms and atypical etiology, pronounced clinical manifestations, the course against a background of severe predisposing conditions (diabetes mellitus, cancer, blood diseases, immunodeficiency, including HIV infection), t. е. cases, poorly amenable to therapy.

Secondary vulvovaginal candidiasis usually includes cases of the infection combined with an existing non-infectious lesion of the genitalia, such as lichen planus squamous cell, Behcet’s disease, pemphigoid.

As a rule, candidiasis symptoms develop rapidly, a week before menstruation and subside somewhat during menstruation. In the chronic persistent form, their intensity increases.

In terms of differential diagnosis, the other two most common vaginal infections have similar symptoms — Bacterial vaginosis and trichomoniasis.

Symptoms of bacterial vaginosis usually appear during the first week of the menstrual cycle and subside on their own in the middle of the cycle. Relapse of bacterial vaginosis sometimes follows a relapse of vaginal candidiasis.

Acute trichomoniasis is characterized by itching and more pronounced burning. The discharge tends to be more profuse, liquid, and frothy.

Microscopy of a native preparation or stained smear — The easiest and most accessible method of detecting the fungus, its mycelium and spores. Cultural diagnosis is recommended only in some cases:

  • To confirm the diagnosis in case of a negative microscopy result and the presence of a typical clinic;
  • for species identification when atypical etiology is suspected;
  • For antimycotic sensitivity testing (usually along with species identification).

Excretion greater than 1•10 4 CFU/mL in the absence of a clinical picture is considered asymptomatic colonization (candida nosivity), but no treatment is prescribed (10–25% of the population are transient carriers of Candida in the oral cavity, 65–80% — in the intestine, 17% — in the detritus of gastroduodenal ulcers). However, in the presence of predisposing (provoking) factors (e.g., antibiotics, chemo-, radiation, steroids, etc.), it is effective in preventing candidiasis. immunosuppressive therapy) is often prophylactic (preventive) treatment. A widely used prophylactic drug is nystatin. However, it is effective in preventing candidiasis only in the intestinal lumen. Its systemic absorption is no more than 3–5%, so it is not able to affect fungi that are not in the intestinal lumen. To prevent urogenital candidiasis, local forms of antimycotics (vaginal pills and suppositories, solutions and ointments) are preferred. In the prevention of candidiasis in persons with severe diseases that are considered predisposing factors (diabetes mellitus), only systemic azoles and amphotericin may be really effective.

Anticandidal drugs include:

  • polyenes — nystatin, levorin, amphotericin;
  • imidazoles — ketoconazole, clotrimazole, miconazole, bifonazole, isoconazole;
  • triazoles — fluconazole, itraconazole;
  • others — Flucytosine, nitrofungin, decamine, iodine preparations, etc.

Most cases of vulvovaginal candidiasis are treatable with topical antifungals and antiseptics.

Topical agents have the advantage of safety, since systemic absorption is practically negligible, while at the same time very high concentrations of the antimycotic are created directly in the affected area, i.e. е. On the mucosal surface.

Vaginal creams are recommended for the treatment of vulvitis, tablets and suppositories — vaginitis.

When treating pregnant women, topical antimycotics may be prescribed only in the second and third trimesters, as indicated. Systemic antimycotics in pregnancy are not recommended.

Concomitant infections or disorders of the vaginal microbiocenosis are quite common in candida vulvovaginitis. In such cases, combined drugs are used, which are highly clinically effective and can be successfully used in the treatment of vulvovaginitis of mixed etiology. Among these drugs, the most popular are:

  • Travocort — isoconazole nitrate + difluorocortolone-21-valerate;
  • Clion-D — miconazole + metronidazole;
  • macmiror complex 500 — nystatin + nifuratel;
  • Poliginax — Nystatin + neomycin + polymyxin;
  • Terginan — Nystatin + neomycin sulfate + ternidazole + prednisolone.

However, combined forms are not recommended for use abroad because, according to some researchers, they worsen pharmacokinetics due to competition of the components of the combination drug. In such cases, a combination of local treatment and systemic.

Local antiseptics are also used in the therapy of vulvovaginal candidiasis:

  • solutions of soda, boric acid, sodium tetraborate, potassium permanganate (for douches and tampons), aniline dyes (for lubrication in mirrors);
  • suppositories — Povidone-iodine (betadine, vocadine, iodoxide) — at night;
  • vaginal capsules — boric acid 600 mg/day;
  • Corticosteroid creams (class I and II).

In severe vulvitis warm baths with soda and local corticosteroid creams of classes I and II are prescribed. Excellent results in the course of therapy can be achieved by applying in severe vulvitis cream travocort, which contains antimycotic isoconazole in combination with a class II corticosteroid diflucortolone-21-valerate. This optimal combination allows a rapid relief of symptoms in women and especially in men. This cream is convenient to use because it is prescribed only once a day (at night) in women and twice (morning and evening) — in men. Travocort is odorless and does not stain underwear.

Highly active class III and IV corticosteroid ointments are not recommended because they can lead to exacerbation, exacerbation of symptoms. Pathogenetic therapy also includes the use of antihistamines and ketotifen.

In persistent cases and in disseminated candidiasis, systemic therapy is preferred, and in some cases — a combination of systemic and topical treatment.

Fluconazole preparations are «the gold standard» in the treatment of patients with candidiasis. Itraconazole and ketoconazole are also used to treat this pathology.

During pregnancy and lactation, the use of systemic drugs is not recommended, and the references to positive results in some works are not proven by a sufficient number of observations and scientific studies.

The duration of systemic therapy for uncomplicated vulvovaginal candidiasis is minimal (single administration, or no more than 5 days of oral medication).

A general recommendation for the treatment of complicated forms is to lengthen the course of therapy (the amount of local and systemic therapy is doubled).

Based on our own experience, we have proposed treatment regimens for uncomplicated and complicated vulvovaginal candidiasis (Tablets.).

Our observations suggest that relapse prevention methods using both topical and systemic medications are most adequate.

Treatment of chronic recurrent vulvovaginal candidiasis

  • Initial course: Diflucan (fluconazole) 50 mg daily for 14 days, or 150 mg every 3 days for 2 weeks (total for the course of 14 tablets of 50 mg or 5 tablets of 150 mg).
  • Prophylactic course: Diflucan (fluconazole) 150 mg once a week for 3 months–4 months.

Treatment of persistent vulvovaginal candidiasis

The initial course is the same as for chronic relapsing candidiasis. Supportive therapy consists of the constant intake of anti-candida drugs: fluconazole (Diflucan), tablets of 150 mg,1–Twice a month for 12–24 months.

In the treatment of candidiasis resistant to antimycotics, if the treatment is not effective, the diagnosis should be confirmed by sampling and reassessment of the pathogen, and then determining the species and sensitivity to antifungal drugs. The choice of systemic or topical antimycotic and its dosage is further carried out in accordance with the results of the study.

After the diagnosis is confirmed again, it is possible to switch to local therapy with antimycotics or antiseptics, prescribed in high doses, often and for long courses.

The use of vitamin complexes containing biotin is also advisable.