Inflammatory diseases of the genital organs negatively affect a woman’s reproductive function and often cause infection of the fetus and newborn. Irrational use of drugs suppresses local immunity, which reduces the resistance of the vaginal biotope and contributes to the growth and progression of the number of colonies of pathogenic microorganisms.
The problem of vaginal candidiasis (VC) has acquired particular relevance. Its frequency in recent years has more than doubled, making up in different regions of Ukraine from 20 to 50% in the structure of infectious pathology of the lower genital organs.
There is evidence that with recurrent VC, the gastrointestinal tract serves as a reservoir of fungi and a source of vaginal reinfection. According to another point of view, the activation of endogenous fungal infection due to a violation of the protective role of the normal microflora of the vagina plays a leading role in the development of VC. VK often manifests itself with local or systemic antibiotic use. Apparently, a decrease in the titer of lactobacilli with the loss of the characteristic acidic environment of the vaginal biotope forms favorable conditions either for the primary penetration of fungi into the vagina, or for their intensive reproduction. VC develops against the background and exacerbates local suppression of cellular and humoral immunity under the influence of a high level of prostaglandins E2 and a decrease in interleukin-2 production. In addition, due to the presence of estrogen-binding proteins in Candida albicans, there are disturbances in the effects of estrogen at the level of vaginal cells. This damages the protective barrier on the part of the vaginal epithelium due to a decrease in the colpotrophic effect of estriol. A decrease in the content of interleukin-2 also has a systemic effect in chronic candidiasis, which leads to a violation of the synthesis of neurosteroids and neurotransmitters in the central nervous system.
Candidal infection impairs the proliferation and maturation of oligodendroglial elements as the main source of synthesis of biologically active substances in the brain, and most patients with chronic candidiasis have polyendocrine disorders, including premenstrual syndrome. The presence of VC aggravates the course of the underlying disease in women with menstrual irregularities, hyperplastic endometrial processes, climacteric syndrome.
The most common in the clinic are candidal vulvovaginitis, cervicitis and urethritis.
It is customary to isolate the acute form of VC, when the duration of the disease does not exceed 2 months, and the chronic, lasting more than 2 months. Currently, chronic vaginal candidiasis accounts for about 50-60% of all cases of the disease, and the recurrence rate reaches 25%.
Chronization of VC can be facilitated by a combination of candidiasis and trichomoniasis, since Trichomonas have the ability to keep undigested pathogenic microorganisms, including Candida, for a long time, forming a kind of “reserve” for reinfection.
Endocrine pathology, primarily disorders of carbohydrate metabolism (diabetes mellitus, metabolic syndrome X), as well as hyperandrogenism often accompanying these diseases, obesity, taking combined oral contraceptives and menopause contribute to the accumulation of glycogen in the vaginal epithelium. This allows the yeast fungi to persist on the cells of the deep layers of the vaginal epithelium, complicating therapy and facilitating chronicity. At the same time, Candida albicans is more often found in patients with type I diabetes, and Candida glabrata in women with type II diabetes.
Clinically, VC (usually acute) is manifested by itching and burning in the vagina, profuse cheesy leucorrhoea, and dyspareunia. On examination, there is swelling and hyperemia of the vaginal mucosa with whitish deposits of pseudomycelium filaments and desquamated epithelial cells, long-term non-healing abrasions and ulceration. However, it should be borne in mind that in about half of the cases, chronic candidiasis has an erased oligosymptomatic course.
The diagnosis is based on complaints, history data, objective research and laboratory methods, primarily bacterioscopy of vaginal discharge. Laboratory confirmation is extremely important, since the opinion formed by the majority of gynecologists “candidiasis is abundant cheesy leucorrhoea” is only partially correct. Only in half of the cases, this clinical sign is due to vaginal candidiasis [6].
The presence of mycelium and spores in wet smears treated with 10% KOH solution confirms the diagnosis. It is possible to use a bacteriological culture method, the material for research in which are whitish films and tiny plaque from the mucous membrane of the vagina, cervix and external genital organs. The use of bacteriological express diagnostic kits is very promising, it does not require a lot of time, it is not difficult to carry out such analyzes, but it is associated with certain material costs. They are based on a qualitative reaction of the nutrient medium, leading to its staining brown in the presence of Candida growth.
Depending on the state of the vaginal microcenosis, three forms of Candida infection of the vagina are distinguished:
Asymptomatic candida infection, in which there are no clinical manifestations of the disease, yeast-like fungi are detected in a low titer (less than 104 CFU / ml), and lactobacilli are absolutely dominant in the composition of microbial associates of vaginal microcenosis. quantity;
True candidiasis, in which fungi act as a mono-pathogen, causing a clinically pronounced picture of vaginal candidiasis. At the same time, in the vaginal microcenosis, Candida fungi are present in a high titer (more than 104 CFU / ml) along with a high titer of lactobacilli (more than 106 CFU / ml) and in the absence of diagnostically significant titers of any other opportunistic microorganisms;
Combination of VC and bacterial vaginosis, in which yeast-like fungi are involved in polymicrobial associations as causative agents of the disease. In these cases, yeast-like fungi (more often in a high titer) are detected against the background of a massive amount (more than 109 CFU / ml) of obligate anaerobic bacteria and gardnerella with a sharp decrease in the concentration or absence of lactobacilli.
Treatment of VC is carried out in several directions at once:
elimination or weakening of the influence of risk and pathogenetically significant factors;
etiotropic therapy with antimycotic drugs;
restoration of normal microflora of the vaginal biotope.
In this case, both specific and non-specific methods of treatment are used.
Nonspecific methods of therapy include well-known drugs: sodium tetraborate in glycerin, Castellani liquid, gentian violet, etc. The action of the above drugs is based on the maximum removal of mycelial forms of the fungus from the crypts of the vagina, as well as on violation of the process of attachment of the fungus to the vaginal wall and inhibition of reproduction. It should be emphasized that all these drugs are not etiotropic due to the fact that they do not possess fungicidal and fungistatic effects. In addition, the disadvantage of these methods is the need for medical procedures by medical personnel, multiple treatments, which in turn can lead to the fact that there is a risk of delay in the crypts of the vagina of fungal cells, and hence more frequent recurrence of the process.
Specific antifungal agents are available in dosage forms for internal and external use. They are represented by preparations of polyene (nystatin, levorin, amphotericin B, natamycin), imidazole (ketoconazole, clotrimazole, bifonazole) and triazole (fluconazole, intraconazole) series, as well as drugs from other groups (griseofulvin, nitroflungintozin), …
The action of fluconazole is aimed at inhibiting the sterol biosynthesis of the fungal membrane. The drug binds a group of heme dependent on cytochrome P-450 of the enzyme lanosterol-14-demethylase of the fungal cell, disrupts the synthesis of ergosterol, as a result of which the growth of fungi is inhibited. In this case, fluconazole selectively acts on the fungal cell, does not affect the metabolism of sex steroids. Concomitant use of fluconazole with oral contraceptives does not affect the effectiveness of the latter.
The leading triad of pathogens (C. albicans, C. parapsilosis, C. tropicalis) is the cause of more than 95% of candidiasis of all localizations and among the fungi of the genus Candida it is most sensitive to fluconazole.
It should be emphasized that the pharmacokinetic characteristics of drugs containing fluconazole, when taken orally and intravenously, are similar, which distinguishes them from other antimycotic drugs. The bioavailability of fluconazole is high and reaches 94%. Fluconazole is well absorbed in the gastrointestinal tract, penetrates the histohematogenous barriers. Its level in blood plasma after oral administration reaches 90% of that with intravenous administration.
It is important to note that the absorption of the drug from the intestine is independent of food intake.
Considering the long half-life of fluconazole from plasma (about 30 hours), this drug can be administered once, which determines its advantage over other antimycotic agents (already 2 hours after taking the drug, the therapeutic concentration in plasma is reached, and after 8 hours – in the vaginal contents) … The activity persists for at least 72 hours.
Recently, there has been a decrease in the effectiveness of all antimycotics and triazoles in the treatment of Candida non-albicans, which sometimes forces a change in the traditional scheme of prescribing fluconazole in the direction of increasing the “loading” dose to 200 mg.
While taking antimycotic drugs, patients with chronic vaginal candidiasis need a protein-vitamin diet with limited carbohydrate intake. The appointment of multivitamins and topical probiotics, for example, dried microbial mass of lactobacilli, is also shown. The use of a vaccine made from inactivated minus variants of lactobacilli has become widespread. Their use in 90% of cases provides a confirmed bacteriologically clinical recovery.
In the “first aid kit” of every obstetrician-gynecologist there is an arsenal of favorite means and treatment regimens for VC. At the same time, the leading role in their assessment is assigned to compliance in patients. Fluconazole is one of the few drugs that is not only effective in treating candidiasis, but also safe. This gives reason to consider it the # 1 drug in monotherapy. Fluconazole is preferable from the standpoint of pharmacoeconomics, it is safe in the treatment of VC, including in patients with a chronic recurrent form of this disease.