Today, the importance of timely diagnosis, treatment and prevention of mycoses of smooth skin, in particular mycoses of the feet, is beyond doubt. The relevance of this problem is due to its widespread prevalence with a steady upward trend in incidence, a tendency to a long progressive course and a high frequency of relapses [1]. According to various expert estimates [2], 10-20% of the adult population suffer from mycoses of the feet. The prevalence of the disease in men is 2 times higher than in women. The prevalence of this infection increases significantly in elderly and senile age groups. In people 70 years of age and older, mycosis of the feet occurs in every second person. Moreover, in recent years there has been a tendency to increase the incidence of mycoses not only in adults, but also in children [3].
Another aspect that determines the relevance of this problem is the increase in the number of patients with so-called dermatoses of combined etiology (secondary infected dermatoses), when, against the background of a chronic skin disease (eczema, atopic dermatitis, psoriasis, erysipelas), leading to disruption of the barrier function of the skin, mycosis develops. This is especially true for certain localizations: folds, feet. In everyday clinical practice, a dermatologist most often encounters superficial mycoses affecting the feet and large folds - dermatophytosis, the causative agents of which can be fungi of the genus Trichophyton
,
Microsporum
or
Epidermophyton
. These microorganisms cannot use carbon dioxide from the air for their nutrition and therefore require ready-made organic substances. The optimal nutritional substrate for them is keratin, which is found in large quantities in the stratum corneum of the skin and its appendages.
Background conditions in the development of mycoses include various immunodeficiency states (HIV infection, paraneoplastic processes, long-term use of immunosuppressive drugs), endocrinopathies, and infectious diseases. Thus, in patients with diabetes, mycosis of the feet occurs 2.8 times more often than in people of the same age and gender who do not suffer from this endocrinopathy. Increased risk factors for the development of mycosis of the feet include microcirculation disorders (in diseases of the vessels and veins of the lower extremities), joint pathology (osteoarthrosis, hallux valgus)
), constant trauma to the skin, excessive sweating or, conversely, dry skin, leading to a decrease in the protective properties of the skin barrier [4].
Regarding the predominant causative agents of foot mycoses, the undisputed leader in etiology is Trichophyton rubrum
[5]. A long course without timely diagnosis and adequate treatment contributes to the involvement of the nail plates in the pathological process; in the future, there may be an alternation of the transition of infection from both the form of mycosis of the skin of the feet, which is the most contagious form, to onychomycosis, which is the most difficult form in terms of treatment, and vice versa . In this aspect, preventive (public, personal) measures, the basis for which can be considered identification of the source of infection and effective treatment, are a priority, since this infection is classified as anthroponotic.
Issues of the effectiveness of various methods of treating foot mycoses and indications for use are constantly discussed at Russian and international conferences, which is reflected in periodically updated clinical recommendations. However, the basic principles of treatment of patients with mycoses of the feet, including three main approaches (systemic, local, combination therapy) remain unshakable, in contrast to the criteria for their prescription. As data from surveys of patients with mycoses of the feet show, most of them prefer topical therapy to systemic therapy (5:1), while many self-medicate. Thus, among patients who took any medications without a doctor’s prescription, 77.6% of patients used external medications, and 24.3% used systemic medications [6]. The main points limiting the use of systemic antimycotics are side effects and the cost of the course of treatment, apparently these are the leading aspects of adherence to topical therapy among patients. When prescribing therapy, specialists must be guided by objective clinical and laboratory criteria that determine the indications for prescribing a particular type of therapy. Systemic methods for mycosis of the feet are indicated in case of ineffectiveness of external treatment, recurrent course and involvement of the nail plates in the process. In other cases, therapeutic measures may be limited to external treatment. Certain difficulties in choosing patient management tactics arise due to the availability of a wide range of antimycotic drugs with unclear and sometimes contradictory recommendations for their use. In any case, topical antifungal therapy remains the most widely used treatment for athlete's foot. It is also necessary to understand that timely treatment is the prevention of onychomycosis and in any case will be obviously more effective and more economically acceptable than treatment of onychomycosis of any severity. In the latter case, acceptable effectiveness with minimal costs and treatment time can be achieved only if the severity of the disease is less than 6 KIOTOS index values [6].
Currently, a fairly large number of systemic and topical antimycotic drugs (cream, varnish, solution) are registered. Depending on their chemical structure, they are divided into several groups (azoles, polyene antibiotics, allylamines, and others), known under different trade names and differ in their spectrum of activity and features of clinical use [7]. In this regard, the practicing physician faces a rather difficult task when choosing a topical drug, while the priority factor can be considered the optimal efficiency/safety ratio and a wide spectrum of action, including against possible contamination with various pathogens (mixed infection). Therefore, drugs that, along with an antimycotic effect, have specific activity against the accompanying microflora deserve special attention.
For the treatment of mycosis of smooth skin, including mycosis of the feet of dermatophytic and mixed etiology, one of the antifungal drugs registered in Russia is Zalain
(sertaconazole).
Sertaconazole contains an azole matrix and a fundamentally new compound - benzothiophene. Sertaconazole, even in relatively low concentrations (the minimum inhibitory concentration is within a fairly narrow range of values for the causative agents of all major skin mycoses and does not exceed 1 μg/ml), has a pronounced antifungal effect against the causative agents of mycoses, manifested in growth arrest, metabolic disorganization and death of fungal cells, which manifests itself in fungicidal and fungistatic effects. The spectrum of specific activity of Zalain
is quite wide and includes dermatophytes (
Trichophyton, Micro sporum, Epidermophyton
),
Candida
spp.
(including Candida albicans , Candida tropicalis
), as well as
Malassezia
spp. and causative agents of bacterial infections of the skin and mucous membranes (gram-positive strains of staphylo- and streptococci) [8].
The fungicidal effect of sertaconazole is due to the fact that one of its components (benzothiophene) has a structural similarity to tryptophan. This promotes the penetration of sertaconazole into the plasma membrane of the fungus. By damaging the cell wall of the fungus, benzothiophene causes the formation of funnels and tunnels in it. Destruction of the plasma membrane causes destruction of the cell skeleton and death of its contents as a result of lysis of organelles. The action of benzothiophene may explain the fungicidal activity of sertaconazole at low concentrations, which distinguishes the drug from other imidazole derivatives, as well as its effectiveness against fungal strains with cross-resistance to imidazoles. The main effect of the latter is due to the effect on the biosynthesis of ergosterol, which only leads to the suppression of fungal growth.
The fungistatic effect is associated with the azole matrix of sertaconazole, which, like other azoles, disrupts the synthesis of ergosterol in the cell membrane of fungi. Ergosterol is formed as a result of biosynthesis from simpler substances through a chain of reactions that includes the synthesis of the intermediate substance lanosterol. A key role in the conversion of lanosterol to ergosterol is played by the enzyme 14-α-demethylase, which is part of a group of enzymes known collectively as cytochrome P-450. All enzymes of the cytochrome P-450 group contain an iron-containing pigment. It is believed that sertaconazole, like other azole antifungals, binds to the iron atom of the hematin group and inactivates 14-α-demethylase. This leads to disruption of ergosterol synthesis and accumulation of lanosterol and other sterols. Their inclusion instead of ergosterol in the membrane significantly disrupts the structure and function of the fungal cell membrane [9].
The undeniable advantage of the drug is that the toxic effect on the cell membrane is noted within 10 minutes after application, and due to its high lipophilicity, the drug is deposited in the deep layers of the skin, where it remains effective for 48 hours after application. The drug is characterized by high safety due to the lack of systemic absorption and, accordingly, does not have a mutagenic or carcinogenic effect, and does not cause photosensitivity.
Material and methods
Inclusion criteria:
— established diagnosis of mycosis of the feet;
— availability of informed consent.
Non-inclusion criteria:
- increased individual sensitivity to the components of the drug;
— low patient compliance.
On an outpatient basis, we observed 76 patients (44 women and 32 men) aged from 18 to 72 years (average 54.3±8.2 years) with a verified diagnosis of mycosis of the feet. The diagnosis was confirmed by microscopic and cultural examination. T. rubrum was isolated by culture
36.8% had a mixed fungal-bacterial infection of the skin of the feet in various combinations:
T. rubrum
and
Staphylococcus
,
T. mentagrophytes var.
interdigitale and
Staphylococcus
,
T mentagrophytes var.
interdigitale and
Pseudomonas
,
T rubrum, Aspergillus terreus
and
Staphylococcus
.
In 29 (38.2%) patients, an intertriginous form of mycosis of the feet was diagnosed, which was clinically represented by infiltration and maceration of the stratum corneum in the depths of the interdigital folds of the feet and on the lateral surfaces of the fingers, with the formation of superficial erosions and rather deep cracks. The main subjective symptoms in this group of patients were complaints of itching, burning, and soreness. In 26 (34.2%) patients, the clinical picture was dominated by “dry” symptoms of mycosis in the form of a squamous form, in 21 (27.6%) - in the form of a squamous-keratotic form, which was clinically characterized by xerosis, hyperkeratosis, severe desquamation and painful cracks, especially in the heel area.
Depending on the prescribed treatment, patients were divided into three groups comparable in clinical and anamnestic parameters. All patients of group 1 ( n
=27) 2% sertaconazole cream was prescribed to the affected area;
patients of group 2 ( n
= 25) used 1% clotrimazole cream;
in group 3 ( n
=22) - 1% terbinafine cream. The drugs were used 1-2 times a day for an average of 4 weeks. Therapeutic efficacy was assessed (microscopic and cultural studies) before treatment and after 4 weeks of therapy. Clinical symptoms were assessed before treatment and at weeks 1 (D7), 2 (D14), 3 (D21) and 4 (D28) of therapy. Long-term results of observation were 6 months.
Patient monitoring met the standards for this pathology. The effectiveness of the treatment was assessed using highly valid indices of dermatological status: VAS (erythema, infiltration, fissures, desquamation, itching, pain), quality of life using the dermatological quality of life index (DIQL, Finlay, 1994). In accordance with the dynamics of the VAS and DIQL indices, the effectiveness of the treatment was assessed as follows: clinical remission - a decrease in the index by more than 95%; significant improvement - reduction of the index to 94-75%; improvement - a decrease in the index by less than 74-50%; 49-30% - slight improvement, no effect - a decrease in the index by less than 29%, deterioration - maintenance of negative dynamics or further progression of the process.
The work also included a survey of patients (doctors) about the convenience and comfort of using 2% sertaconazole cream ( Zalain
).
Analysis and processing of statistical data was carried out using the nonparametric Friedman method and the Mann-Whitney test. Statistical data analysis was carried out using SPSS v.21 and Prism 6 Graphpad programs. Differences at p
<0,05.
results
In group 1, after 1 week of therapy (D7), positive dynamics were observed in relation to all clinical symptoms of mycosis. Thus, the severity of erythema decreased by 16.7% from 3.6 (Q1=3.2; Q3=4.0) to 3.0 (Q1=2.8; Q3=3.2) points, infiltration decreased by 13 .2% - from 3.8 (Q1=3.4; Q3=4.2) to 3.3 (Q1=3.1; Q3=3.5) points. At visit D14, VAS erythema and VAS infiltration decreased by 55.7 and 44.1%, respectively ( p
<0.01), compared with D0 indicators.
After 4 weeks (D28), the VAS erythema index was reduced by 95.4% - to 0.2 (Q1=0.1; Q3=0.3) points ( p
<0.05), VAS infiltration - by 93.1% up to 0.3 (Q1=0.1; Q3=0.5) points (
p
<0.05) (Fig. 1).
Rice.
1. Average indicators (scores) of the severity of erythema/infiltration after application (visit D28) of 2% sertaconazole cream (according to the dynamics of the VAS index). Note. Here and below: the ordinate axis shows the median values (p<0.05) in accordance with the Mann-Whitney test. In groups 2 and 3, after 1 week of therapy (D7), significant positive dynamics were also observed, but to a lesser extent. Erythema decreased by 10.8 and 5.7%, respectively - from 3.7 (Q1=3.4; Q3=4.0) to 3.3 (Q1=3.0; Q3=3.6) and 3. 5 (Q1=3.2; Q3=3.8) to 3.3 (Q1=3.1; Q3=3.5) points, infiltration decreased by 10.2 and 11.5%, respectively - from 3.9 (Q1=3.7; Q3=4.1) up to 3.5 (Q1=3.3; Q3=3.7) and 4.0 (Q1=3.8; Q3=4.2) up to 3, 5 (Q1=3.3; Q3=3.7) points. At visit D14 in group 2, the VAS erythema and VAS infiltration indices decreased by 34.6 and 32.3%, respectively ( p
<0.01) in comparison with D0 indicators.
In group 3, the reduction was 33.5 and 33.7%, respectively. After 4 weeks (D28) in group 2, the VAS erythema index was reduced by 83.8% - to 0.6 (Q1=0.5; Q3=0.7) points with ( p
<0.05), VAS infiltration reduced by 89.7% - to 0.4 (Q1=0.2; Q3=0.6) points (
p
<0.05), in the 3rd group VAS erythema was reduced by 85.7% - to 0, 5 (Q1=0.3; Q3=0.7) points (
p
<0.05), VAS infiltration was reduced by 90.0% - to 0.4 (Q1=0.3; Q3=0.5) points (
p
<0.05) (Fig. 2, 3).
Rice. 2. Average indicators (scores) of the severity of erythema/infiltration (visit D28) (according to the dynamics of the VAS index) in the 2nd group.
Rice.
3. Average indicators (scores) of the severity of erythema/infiltration (visit D28) (according to the dynamics of the VAS index) in the 3rd group. In group 1, after 1 week of therapy (D7), there was a pronounced positive trend in relation to desquamation: the VAS index decreased by 18.2% - from 4.4 (Q1=4.0; Q3=4.8) to 3. 6 (Q1=3.4; Q3=3.8) points, the severity of cracks decreased by 19.8% - from 2.5 (Q1=2.4; Q3=2.6) to 2.0 (Q1= 1.8; Q3=2.2) points. At visit D14, the VAS desquamation and VAS fissure indices decreased by 58.4 and 57.9%, respectively ( p
<0.05) in comparison with D0 indicators.
After 4 weeks (D28), VAS desquamation was reduced by 86.4% - to 0.6 (Q1=0.5; Q3=0.7) points ( p
<0.05), VAS fissure was reduced by 92.1% - up to 0.2 (Q1=0.1; Q3=0.3) points (
p
<0.05) (Fig. 4).
Rice.
4. Average indicators (scores) of the severity of desquamation/cracks after application (visit D28) of 2% sertaconazole cream (Zalain) according to the dynamics of the VAS index. In groups 2 and 3, after 1 week of therapy (D7), less pronounced positive dynamics were noted than in group 1, both in terms of desquamation (VAS index decreased by 8.7% - from 4.5 (Q1= 4.1; Q3=4.9) to 4.0 (Q1=3.9; Q3=4.2) points and by 9.0% from 4.4 (Q1=4.2; Q3=4.6 ) to 4.0 (Q1=3.9; Q3=4.2) points, respectively, and the severity of cracks by 8.6% from 2.3 (Q1=2.1; Q3=2.5) to 2 .0 (Q1=1.8; Q3=2.2) points and by 9.2% from 2.5 (Q1=2.3; Q3=2.7) to 2.3 (Q1=2.0; Q3=2.6) points. At visit D14 in group 2, VAS desquamation and VAS fissures decreased by 44.2 and 41.9%, respectively ( p
<0.05) in comparison with D0 indicators.
In group 3, VAS desquamation and VAS cracks decreased by 45.1 and 42.2%, respectively ( p
<0.05), compared with D0 values.
After 4 weeks (D28) in group 2, the VAS desquamation index was reduced by 86.7% - to 0.6 (Q1=0.5; Q3=0.7) points ( p
<0.05), VAS fissures was reduced by 90.3% - up to 0.2 (Q1=0.1; Q3=0.3) points (
p
<0.05).
After 4 weeks (D28) in the 3rd group, VAS desquamation was reduced by 88.6% - to 0.5 (Q1=0.4; Q3=0.6) points ( p
<0.05), VAS fissures was reduced by 91.8% - up to 0.2 (Q1=0.1; Q3=0.3) points (
p
<0.05) (Fig. 5, 6).
Rice. 5. Average indicators (scores) of the severity of desquamation/cracks (visit D28) according to the dynamics of the VAS index in group 2.
Rice.
6. Average indicators (scores) of the severity of desquamation/cracks (visit D28) in group 3 according to the dynamics of the VAS index. Similar dynamics in group 1 were noted with regard to subjective symptoms of mycosis of the feet. Thus, after 1 week of therapy (D7), VAS itching decreased by 43.4% - from 5.3 (Q1=5.0; Q3=5.6) to 3.0 (Q1=2.8; Q3=3, 2) points, VAS pain decreased by 14.6% - from 4.1 (Q1=4.0; Q3=4.2) to 3.5 (Q1=3.2; Q3=3.8) points. At visit D14, VAS itching and VAS pain decreased by 78.4 and 32.3%, respectively ( p
<0.05), compared with D0 indicators.
After 4 weeks (D28), VAS itching was reduced by 100% to 0 points ( p
<0.05), VAS pain was reduced by 100% to 0 points (
p
<0.05) (Fig. 7).
Rice.
7. Average indicators (scores) of the severity of itching/pain after application (visit D28) of sertaconazole cream (Zalain) according to the dynamics of the VAS index. In groups 2 and 3, after 1 week of therapy (D7), VAS itching decreased by 38.6 and 39.5%, respectively. At visit D14, VAS itching and VAS pain decreased by 72.5 and 65.7%, respectively, and 69.4 and 68.5%, respectively ( p
<0.05) in comparison with D0 indicators.
After 4 weeks (D28) in the 2nd group, VAS itching was reduced by 98.9 and by 98.1% in the 3rd group and amounted to 0.1 (Q1=0.0; Q3=0.2) points ( p
<0.05), VAS pain was reduced by 100% to 0.0 points (
p
<0.05) (Fig. 8, 9).
Rice. 8. Average indicators (scores) of the severity of itching/pain (visit D28) in group 2 according to the dynamics of the VAS index.
Rice.
9. Average indicators (scores) of the severity of itching/pain (visit D28) in group 3 according to the dynamics of the VAS index. Based on the total reduction of VAS indices (erythema, infiltration, desquamation, cracks, itching, pain) after 2 weeks of therapy (D14), the effectiveness of treatment in group 1 was 68.2%, and after 1 month (D28) it reached 96.2% . 2 (7.4%) patients with squamous-keratotic form of mycosis of the feet responded to the therapy torpidly, for whom therapy was extended to 6 weeks. Special methods (microscopic and cultural studies) at visit D28 showed elimination of the pathogen in 100% of cases. In no clinical case, side effects or complications from the use of 2% sertaconazole cream were observed in patients. High clinical effectiveness was accompanied by an improvement in the quality of life of patients. Thus, the DIQI index decreased by 80.3% - from 14.2 (Q1=13.0; Q3=15.4) to 2.8 (Q1=2.6; Q3=3.0) points.
In group 2, after 2 weeks of therapy (D14), the effectiveness of treatment was 59.6%, and after 1 month (D28) it reached 88.0%. In group 3, after 2 weeks of therapy (D14), the effectiveness of treatment was 62.1%, and after 1 month (D28) it reached 86.4%. The quality of life index of patients also improved significantly: in group 2 by 78.2% - from 15.1 (Q1=13.3; Q3=16.9) to 3.3 (Q1=2.9; Q3=3 .7) points, in the 3rd group by 76.1% - from 14.6 (Q1=13.8; Q3=15.6) to 3.5 (Q1=2.9; Q3=4.1) points. Special methods (microscopic and cultural studies) at visit D28 showed elimination of the pathogen in the 2nd group in 92.0% of cases, in the 3rd group - in 90.1% of cases.
These data were fully consistent with the survey data of the doctors who conducted the study and the patients themselves: 94.4 and 94.7%, respectively, noted good or very good effectiveness and ease of use of Zalain
(Fig. 10). Compliance was 100%: not a single patient stopped using the cream due to low effectiveness or inconvenience of using the drug.
Rice.
10. Data from a survey of doctors/patients to assess the effectiveness and comfort of using sertaconazole cream (Zalain) at visit D28. Long-term results of observations for 6 months after a course of therapy with sertaconazole showed a high preventive orientation - there were no relapses of the disease in 100% of patients. In group 2, 3 (12%) patients and in group 3, 2 (9.1%) patients had a relapse of the disease.
Sertaconazole in the treatment of acute vulvovaginal candidiasis
Yeast-like fungi of the genus Candida belong to the normal microflora of the vagina and are opportunistic microorganisms. Normal vaginal microflora implies the following: the average number of aerobic and anaerobic microorganisms in vaginal discharge is normally 105–108 CFU/ml, and their ratio is 10:1. In the vaginal microbiocenosis of women of reproductive age, peroxy-producing lactobacilli predominate (95–98%). By colonizing the vaginal mucosa, lactobacilli participate in the formation of an environmental barrier and thereby ensure the resistance of the vaginal biotope. The main mechanism that ensures colonization resistance of the vaginal biotope is their ability to form acids. Normally, the pH of the vaginal environment is 3.8–4.5. In addition, the protective properties of lactobacilli are realized in different ways: due to antagonistic activity, adhesive properties, and the ability to produce lysozyme and hydrogen peroxide. In the presence of a number of unfavorable factors, fungi acquire pathogenic properties and cause diseases. The development of CV can be caused by changes in hormonal levels due to: increased glycogen content in epithelial cells; pH shifts; direct stimulating effect of estrogens on fungal growth (pregnancy, long-term use of oral contraceptives), increasing the avidity of the vaginal epithelium to fungi, which contributes to their better adhesion; suppression of immune defense mechanisms. One of the main risk factors is antibiotic therapy, not only oral and parenteral use of drugs, but also their local use. Various conditions leading to suppression of the immune system of the macroorganism, for example, hypovitaminosis, chronic diseases, injuries, surgeries, taking antibiotics, cytostatics, radiation therapy, can also contribute to the development of LE. The species of greatest importance in the occurrence of vulvovaginitis is C. albicans, which causes disease in 80–95% of cases. In 54–76% of cases, the causative agents are C. glabrata, C. tropicalis, C. parapsilosis, C. krusei. Yeast-like fungi of the genus Candida belong to the family Cryptococcaceae. Fungal cells have a round or oval shape, sizes vary from 1.5 to 10 microns. Yeast-like fungi do not have true mycelium; they form pseudomycelium, which is formed due to the elongation of fungal cells and their arrangement in a chain. The pseudomycelium is devoid of a common shell and partitions. Yeast-like fungi at the junctions of the pseudomycelium can bud blastospores (groups of budding cells), and flask-shaped swellings can form inside the pseudomycelium, from which chlamydospores are formed. During the process of invasion, blastospores of yeast-like fungi are transformed into pseudomycelium. Yeast-like fungi are aerobes. The most favorable temperature for their growth is 21–37°C, pH 6.0–6.5. Yeast-like fungi of the genus Candida die when boiled for 10–30 minutes, withstand exposure to dry steam at a temperature of 90–110°C for 30 minutes, and can remain in very acidic environments (pH 2.5–3.0) for a long time, although their development slows down. The following stages are distinguished in the development of candidal infection: • attachment (adhesion) of fungi to the surface of the mucous membrane with its colonization; • germination into the epithelium; • overcoming the epithelial barrier of the mucous membrane; • entry into the connective tissue of the lamina propria; • overcoming tissue and cellular protective mechanisms; • penetration into blood vessels; • hematogenous dissemination with damage to various organs and systems. With CV, pseudomycelium penetrates deep into the epithelium. At this level, the infection can persist for a long time, because a dynamic balance is established between fungi, which cannot penetrate into the deeper layers of the mucous membrane, and the macroorganism, which restrains this possibility, but is not able to completely eliminate the pathogen. Violation of this balance leads either to an exacerbation of the disease, or to recovery, or to remission. There are three forms of CV. Candidateship. There are no complaints or pronounced clinical picture of the disease. During microbiological examination, small amounts of budding forms of yeast-like fungi are found in vaginal discharge in the absence of pseudomycelium in most cases. Candidate carrier status can develop into a clinically pronounced form. Acute form of CV. The duration of the disease does not exceed 2 months. The clinical picture is dominated by pronounced signs of local inflammation of the vulva: hyperemia, swelling, discharge, itching and burning. Chronic form of CV. The duration of the disease is more than 2 months, while infiltration, lichenification, and atrophy are pronounced on the mucous membranes of the vulva and vagina. Depending on the state of the vaginal microcenosis, three forms of Candida infection of the vagina are classified. • Asymptomatic candidiasis: there are no clinical manifestations of the disease, yeast-like fungi are detected in a low titer (≤102 CFU/ml), and the microbial associates of the vaginal microcenosis are dominated by lactobacilli in a moderately large number - 106–108 CFU/ml. • True candidiasis: fungi act as a monopathogen, causing a clinically pronounced picture of CV. Yeast-like fungi are present in a titer of >102 CFU/ml, lactobacilli are present in a high titer (>108 CFU/ml). There are no other microorganisms; opportunistic microorganisms are present in diagnostically insignificant quantities. • Combination of CV and bacterial vaginosis: yeast-like fungi participate in polymicrobial associations as causative agents of the disease. Fungi of the genus Candida are found in high titers (>104 CFU/ml) against the background of a massive amount (>109 CFU/ml) of obligate anaerobic bacteria and Gardnerella with a sharp decrease in the concentration or absence of lactobacilli. In the clinic, the main symptom of CV is cheesy deposits of gray-white color, with a sour odor, pinpoint or 5–7 mm in diameter, sometimes merging with each other. The lesions are sharply demarcated, round or oval in outline, as if embedded in the mucous membrane of the vulva and vagina; the plaques contain masses of multiplying Candida fungi. In the acute stage of the disease, the cheesy films “sit” tightly, are removed with difficulty, exposing the eroded surface, and later - easily. Due to their rejection, thick whitish cheesy discharge appears. The mucous membrane in the affected area has a pronounced tendency to bleeding, and along the periphery of the lesion is intensely hyperemic. Itching often bothers patients during menstruation, after physical activity. In some cases, there may be a burning sensation and some pain when urinating. Sharp pain and burning usually bother patients during sexual intercourse, which can lead to the formation of a neurotic syndrome. Microscopic examination allows you to determine the presence of a fungus, its spores, mycelium, and the number of leukocytes. For species identification of the fungus, cultural examination and polymerase chain reaction are required. Treatment is indicated only in the presence of a clinical picture of the disease, confirmed microscopically and culturally. Drugs for the treatment of LE are available in various dosage forms (suppositories, tablets, creams) and are intended for local and/or systemic use. In acute cases, most specialists prefer topical medications. The intravaginal route of therapy is more preferable due to the fact that in this case the drug enters directly into the vagina, colonized by fungi. This ensures high effectiveness of small doses of the drug and eliminates systemic effects on the entire body, which reduces the risk of adverse reactions. Resistance often develops to many of the existing local drugs for the treatment of LE. The main mechanisms of fungal resistance are related to the fact that: • mutated fungal cells produce enzymes that block transport systems; • cells appear with a large number of pumps that release the drug from the cell; • mutated strains produce a substrate at high speed, which is not affected by the antimycotic; • the structure of the target enzyme on which the antimycotic acts changes, and it does not combine with the drug; • fungal cells have (or produce) an alternative enzyme pathway that compensates for the function of the lost enzyme. In vitro studies have shown that there is synergism between some antifungal drugs to overcome the problem of cross-resistance. As a result of the study of these interactions, it became possible to create a fundamentally new antimycotic drug - sertaconazole. Sertaconazole has a wide spectrum of action against pathogens that cause infections of the skin and mucous membranes: pathogenic yeast fungi (Candida albicans, C. tropicalis, C. pseudotropicalis, C. krusei, C. parapsilosis, C. neoformans; Torulopsis, Trichosporon and Malassezia), dermatophytes (Trichophyton, Microsporum and Epidermophyton), filamentous opportunistic fungi* (Scopulariopsis, Altermania, Acremonium, Aspergillus and Fusarium), gram-positive (staphylococci and streptococci, L. monocytogenes) and gram-negative (E. faecium, E. faecalis, Corynebacterium spp. , Bacteroides spp., P. acnes) microorganisms, representatives of the genus Trichomonas. Sertaconazole is highly active against strains of C. albicans serotypes A and B (mean minimum inhibitory concentration (MIC) values of 0.21 and 0.65 μg/ml after 24 and 48 hours, respectively), as well as against moderately sensitive and resistant imidazole derivatives strains. Sertaconazole is a new generation “dual class” antifungal drug. The drug contains two synergistic classes in one molecule: an azole and a benzothiaphene group. Sertaconazole has a fungicidal, fungistatic effect, blocks dimorphic transformation of fungi, has a wide spectrum of action, and is characterized by high compliance. In this case, the imidazole part of the molecule disrupts the biosynthesis of ergosterol, interferes with the cytochrome P450-dependent enzyme C-14a-lanosterol demethylase, inhibits fungal growth, and provides a fungistatic mechanism. The benzothiaphene structure replaces tryptophan in the fungal membrane, which leads to its destruction and death, i.e. fungicidal effect occurs. Thanks to this dual mechanism of action, the risk of relapse is minimal. Topical use of sertaconazole can increase the effectiveness of CV therapy. The treatment regimen involves a single dose of the drug. We observed patients (31 women) aged 19 to 46 years who presented with clinical symptoms of acute LE. Clinically, the diagnosis was confirmed by microscopic examination and cultivation on nutrient media. The diagnosis of acute LE was established based on the presence of clinical manifestations and the detection of Candida fungi in the vaginal discharge of more than 104 CFU/ml. Inclusion criteria were: absence of pregnancy and lactation, use of barrier methods of contraception, absence of other STIs, absence of use of all antifungal drugs, both locally and systemically. After confirmation of the diagnosis, all patients received local monotherapy with sertaconazole in a one-day course: one suppository (300 mg) deep into the posterior vaginal fornix at night. 7 days after the use of sertaconazole, patients underwent repeated microscopic and cultural examination. In the absence of clinical and mycological recovery, a repeated single administration of 300 mg of the drug was prescribed with control after 7 days. Thus, each patient underwent three follow-up examinations after 7, 14 and 30 days. All patients at initial treatment had a curdled discharge - from moderate to strong, itching - from mild to severe. The identified pathogen was C. albicans. Of the nonspecific pathogens, the following were noted: epidermal staphylococcus - in 3 (9.7%) in the amount of 104 CFU/ml; bacteroids – in 8 (25.8%) in the amount of 104–105 CFU/ml; Proteus – in 3 (9.7%) patients. The duration of the disease ranged from 1 to 12 weeks. In 6 patients, accounting for 19.4%, candidiasis occurred due to the use of oral contraceptives, 17% (55) of patients indicated the relationship between the manifestation of the disease and the use of a course of antibiotic therapy. Ten patients indicated previous STIs (chlamydia, trichomoniasis, gonorrhea). 17 (55%) patients had previously reported episodes of acute LE, 10 (32.2%) of them more than once. For local treatment, women used clotrimazole, natamycin, miconazole, most without prior consultation with a specialist. Clinical studies have shown that 25 (80%) patients noted the disappearance or significant reduction in the severity of symptoms of the disease the very next day after using the drug. Slight itching and discharge were noted in 6 patients. They were prescribed a repeat course in the form of a single dose of sertaconazole. No side effects or allergic reactions were observed in any woman when using sertaconazole. Microscopic and cultural examination of vaginal discharge after treatment 7 and 14 days later revealed small amounts of yeast-like fungi in only 4 (12.9%) patients. When presenting 30 days after treatment, all patients showed complete clinical recovery. No nonspecific flora was detected in anyone. Thus, the high effectiveness of sertaconazole in a single dose (in rare cases, double) treatment regimen, its good tolerability, absence of side effects and ease of use allow us to consider this drug one of the best in the antimycotic therapy of acute LE. Literature 1. Clinical recommendations. Dermatovenereology / Ed. A.A. Kubanova. – M.: GEOTAR-Media, 2006. – 320 p. 2. Kurdina M.I. Experience in the treatment of vulvovaginal candidiasis // Bulletin of Dermatology and Venereology. – 2005. – No. 5. – P. 48–53. 3. Prosovetskaya A.L. New aspects in the treatment of vulvovaginal candidiasis // Bulletin of Dermatology and Venereology. – 2006. – No. 6. – P. 31–33. 4. Sergeev A.Yu., Sergeev Yu.V. Candidiasis. – M., 2001. – P. 247–264. 5. Serova O.F., Krasnopolsky V.I., Tumanova V.A., Zarochentseva N.V. Modern approach to the prevention of vaginal candidiasis against the background of antibacterial therapy // Bulletin of Dermatology and Venereology. – 2005. – No. 4. – P. 47–49. 6. Khamaganova I.V. Vulvovaginal candidiasis // Attending physician. – 2007. – No. 3. 7. Lutsevich K.A., Reshetko O.V., Rogozhina I.E., Lutsevich N.F. Clinical effectiveness of sertaconazole (Zalain) in the local treatment of vulvovaginal candidiasis during pregnancy // Ros. Bulletin of obstetrician-gynecologist. – 2008. – No. 3. – P. 77–80. 8. Podzolkova N.M., Nikitina T.I., Vakatova I.A. New antifungal drug Zalain for the treatment of acute vulvovaginal candidiasis // Consilium Medicum. Gynecology. –2006. – T. 8, No. 3. 9. Prilepskaya V.N., Bayramova G.P. Vaginal candidiasis: etiology, clinical picture, diagnosis, principles of therapy // Contraception and health. – 2002. – No. 1. – P. 3–8. 10. Minkina G.N. Treatment of acute candidal vulvovaginitis // Gynecology. –2001. 11. Krasnopolsky V.I., Serova O.F. Clinical effectiveness of orungal for chronic vaginal candidiasis // Ros. Bulletin of obstetrician-gynecologist. – 2003. – No. 1. – P. 30–32. 12. Sergeev A.Yu., Malikov V.E., Zharikov N.E. Etiology of vaginal candidiasis and the problem of resistance to antimycotics // National Academy of Mycology, series “Medical Mycology”. – 2001. 13. Strachunsky L.S., Belousov Yu.B., Kozlova S.N. Antibacterial therapy. Practical guide. – M., 2000. 14. Alimova N.G. Optimization of treatment of acute candidal vulvoginitis in women of reproductive age: abstract, 2009. – P.1–10. 15. Gil–Lamaignere C., Muller FM Differential effects of the combination of caspofungin and terbinafine against Candida albicans, Candida dubliniensis and Candida kefyr // Int. J. Antimicrob. Agents. 2004. Vol. 23, no. 5. P.520–523. 16. Grillot R. Epidemiological survey of Candidemia in Europe // Mycology newsletter. 2003. No. 1. P. 6. 17. Sobel JD Vaginitis // New Engl. J. Med. 1997. Vol. 337. P.1896–1903.
Discussion
Sertaconazole has a wide spectrum of antimycotic activity, which makes it possible to quickly achieve clinical and mycological recovery in patients with various clinical forms of mycosis of the feet; in addition, the drug has pronounced antibacterial activity, which is confirmed by the results of a cultural study. The high lipophilicity of sertaconazole leads to its accumulation in the deep layers of the skin, ensuring that it maintains an effective therapeutic concentration for 48 hours after application. The drug does not have a systemic effect, does not cause side effects and is well tolerated by patients, which has a positive effect on compliance. The duration of the drug is determined individually, depending on the characteristics of the clinical case, and on average is 2-4 weeks; in cases of torpid course, the use of the drug can be extended to 6 weeks. The overall clinical efficacy of sertaconazole 2% cream is 100.0%, which is significantly better than clotrimazole 1% cream (92.0%) and terbinafine 1% cream (90.1%). Complete recovery implies clinical cure with simultaneous eradication of the pathogen. Sertaconazole has a pronounced fungicidal effect, which minimizes the risk of relapses after a course of treatment. The use of sertaconazole causes the eradication of various types of fungi, including the genus Trichophyton rubrum
(often resistant to antifungal therapy, causing relapses), as well as accompanying microflora.
The high therapeutic effectiveness of sertocanozole cream determines its high preventive orientation: complete elimination of pathological microflora. Long-term results of observations for 6 months after a course of therapy with Zalain
showed the absence of relapses in 100% of patients, while after using 1% clotrimazole, relapses were observed in 12%, and after using 1% terbinafine - in 9.1% of cases.
SERTACONAZOLE
Compound:
Active ingredient: sertaconazole;
1 pessary contains sertaconazole nitrate 300 mg;
Excipients: anhydrous colloidal silicon dioxide, solid fat.
Dosage form. Pessaries.
Basic physical and chemical properties: oval pessaries of white or almost white color.
Pharmacological group.
Antimicrobial and antiseptic agents used in gynecology. Imidazole derivatives. ATX code G01A F19.
Pharmacological properties.
Pharmacodynamics.
"Sertaconazole" is an antifungal drug, an imidazole derivative, which has high fungicidal activity and is intended for topical use in gynecology. The mechanism of action is to inhibit the synthesis of ergosterol and increase the permeability of the cell membrane, which leads to the destruction of pathogens. Effective against pathogenic yeast fungi (Candida albicans, Candida spp. and Malassezia furfur), dermatophytes (Trichophyton, Epidermophyton and Microsporium spp.) and pathogens that cause infectious diseases of the skin and mucous membranes, including gram-positive strains (Staphylococcus, Streptococcus ).
Pharmacokinetics.
There is no systemic absorption.
Clinical characteristics.
Indications.
Local treatment of vaginal candidiasis.
Contraindications.
Hypersensitivity to antifungal agents, imidazole derivatives, or to any excipients of the drug.
Simultaneous use of the drug with latex condoms or pessary.
Interaction with other drugs and other types of interactions.
When pessaries are used simultaneously with local contraceptives, their spermicidal effect may be reduced.
Concomitant use with latex condoms or pessaries is not recommended due to the risk of damage.
Features of application.
During treatment, it is not recommended to use soap with an acidic pH; you should use mostly cotton and do not douche. It is also advisable to apply an antifungal cream containing sertaconazole to the vulva and perineum.
When using the drug, it is recommended to abstain from sexual relations. It is recommended to consider the possibility of simultaneous treatment of the sexual partner. Treatment can be carried out during menstruation.
Factors (hygienic or lifestyle) that contribute to the development and manifestations of fungal infection should be identified and eliminated.
It is also recommended to treat other pathogens that may be associated with candidiasis.
Treatment should be discontinued if a local allergic reaction occurs.
In the absence of characteristic signs of vaginal candidiasis, a positive microbiological test in itself is not an indication for treatment.
Use during pregnancy or breastfeeding.
There is no data on the presence of embryotoxicity and teratogenic effect of sertaconazole. Considering the method of administration (single dose of treatment) and the lack of systemic absorption of the drug, the use of sertaconazole in pregnant women is possible provided that the expected benefit to the woman outweighs the potential risk to the fetus.
There is no data on the penetration of sertaconazole into breast milk. The drug should not be used during breastfeeding, unless, in the opinion of the doctor, the expected benefit to the mother outweighs the potential risk to the child.
The ability to influence the reaction rate when driving vehicles or other mechanisms.
Does not affect.
Method of administration and dose.
For adults, insert 1 pessary deep into the vagina in the evening before bedtime, 1 time per day. If the clinical signs of the disease do not disappear, the drug can be re-used after 7 days.
Children.
Sertaconazole is not prescribed to children.
Overdose.
After vaginal use, overdoses were practically not observed.
Adverse reactions.
Sometimes a transient local irritant reaction (burning sensation and itching) may occur. Allergic reactions often occur.
Best before date.
2 years.
Storage conditions.
Store in original packaging at a temperature not exceeding 25 °C.
Keep out of the reach of children.
Package. 1 pessary in a strip made of polyvinyl chloride film. 1 strip in a pack.
Vacation category. On prescription.
Manufacturer. PJSC "Monfarm", Ukraine.
The location of the manufacturer and his address of where his activities are carried out. Ukraine, 19100, Cherkasy region, Monastyrische, st. Zavodskaya, 8.
conclusions
Sertaconazole ( Zalain
) has a wide spectrum of antimycotic action against the main pathogens of mycosis of the feet, including mixed infections, which is confirmed by the elimination of the fungus according to microscopic and bacteriological research methods. The effectiveness of sertaconazole monotherapy for mycosis of the feet is 100% and is confirmed by a reduction in the VAS index (erythema, infiltration, desquamation, cracks, itching, pain). The use of sertaconazole cream is reliably preventive, as evidenced by the absence of relapses of the disease. According to the assessment of the effectiveness and comfort of using sertaconazole cream by the patients themselves, complete satisfaction was noted in 95% of patients, while adherence to treatment was 100%.
There is no conflict of interest.
