Laktozhinal, 100 million CFU, vaginal capsules, 14 pcs.

Compound

Pharmacodynamics

Lactobacillus casei is a type of gram-positive rod-shaped anaerobic non-spore-forming bacteria, normal obligate flora of the oral cavity and intestines; along with other types of lactobacilli (L. acidophilus, L. fermentum, L. cellobiosum, etc.), are represented in the normal flora of a woman’s vulva and vagina.

Colonization of the vagina by living rods L. casei rhamnosus Doderleini creates a similar physiological environment in the vagina. The strain of L. casei rhamnosus Doderleini in the composition of the drug LACTOGINAL has antagonistic activity against a wide range of pathogenic and opportunistic bacteria (including Staphylococcus spp., Proteus spp., enteropathogenic Escherichia coli), improves local metabolic processes and helps restore natural local immunity.

When a LACTOGINAL capsule is introduced into the vagina, the gelatin shell of the capsule dissolves, releasing a lyophilized culture of live lactobacilli. In vitro it has been shown that L. casei rhamnosus Doderleini leads to the necessary decrease in pH within a few hours after administration, helping to restore the natural microflora of the vagina.

Dosage regimen

The drug is used intravaginally. The capsule should be inserted into the vagina, moistened with a small amount of water to accelerate the dissolution of the drug.

To restore normal vaginal microflora after antibacterial therapy for bacterial vaginosis, 1 caps is used. morning and evening for 7 days or 1 caps. daily for 14 days.

In preparation for scheduled gynecological operations; during prenatal preparation of pregnant women at risk for bacterial vaginosis, 1 caps is used. morning and evening for 7 days or 1 caps. daily for 14 days - as part of complex therapy.

The dosage regimen should be adjusted depending on the severity of the clinical effect.

In order to prevent relapses of vulvovaginal candidiasis (including exacerbations of recurrent vulvovaginal candidiasis) after local and/or systemic therapy with antifungal drugs, 1 caps is used. for the night. The duration of drug therapy is determined by the doctor. The course of treatment should not exceed 21 days. The issue of repeat courses is decided individually.

Directions for use and doses

Intravaginally.

Insert the capsule deep into the vagina, moistening it in a small amount of water to accelerate the dissolution of the drug.

For rehabilitation therapy after the use of antibiotics and prevention of bacterial vaginosis: 1 caps. morning and evening for 7 days or 1 caps. daily for 14 days.

In preparation for planned gynecological operations and bacterial vaginosis; prenatal preparation of pregnant women at risk for inflammatory diseases: 1 caps. morning and evening for 7 days or 1 caps. daily for 14 days - as part of complex therapy.

The dosage regimen should be adjusted depending on the severity of the clinical effect.

Currently, much attention is paid to vaginal diseases, especially those caused by opportunistic flora, which include bacterial vaginosis. The prevalence of this pathology ranges from 20 to 80% of all diseases for which patients visit an outpatient gynecologist. Numerous studies have established that vaginal dysbiosis and infections have a direct adverse effect on a woman’s reproductive function. The presence of bacterial vaginosis is associated with inflammatory diseases of the pelvic organs, chorioamnionitis, spontaneous miscarriages [15], non-developing pregnancy, premature birth [4, 6, 15, 18], chronic fetal hypoxia, weakness and incoordination of labor, the development of metroendometritis, peritonitis, sepsis [2, 3, 6, 11, 13, 15]. A decrease in body weight and the development of pneumonia in newborns have been noted [3, 4, 6]. In addition, the presence of bacterial vaginosis reduces the quality of life of women, creates intimate problems and discomfort in the sexual sphere. Normal vaginal microbiocenosis is represented mainly by lactobacilli, a small number of anaerobes and aerobic microorganisms, which are in a state of dynamic equilibrium. The number of lactobacilli in healthy women is 107-108 CFU/ml. It is known that several species of lactobacilli are present in vaginal secretions ( L. acidophyllis, L. casei, L. crispatus, L. gasseri, L. jensenii, L. inserts

and some others). During their life, these bacteria, when breaking down glycogen, produce lactic acid, synthesize hydrogen peroxide, and have adhesive ability, but the severity of these qualities differs among different strains. The maintenance of colonization resistance is ensured by the acid-forming function of lactobacilli and the ability to synthesize hydrogen peroxide.

Antibacterial drugs are widely used in the treatment of patients with bacterial vaginosis, but their use does not guarantee a long-term effect and is often accompanied by relapses of the disease associated with a low number of lactobacilli and insufficient activity of normal microbiocenosis [1, 5, 7, 8-10, 12, 14, 16 , 17]. The tendency of bacterial vaginosis to develop as a recurrent disease creates real difficulties in treating such patients [5, 16]. Often there are asymptomatic forms of bacterial vaginosis, which have no less impact on the state of the reproductive system than those with a pronounced clinical picture [12-15, 21].

Active and unsystematic use of antibiotics in modern medical practice leads to disruption of the vaginal microbiocenosis. The etiology of bacterial vaginosis is currently not fully established. However, it is known that the pathogenesis of the disease is associated with the presence of several microorganisms, with a sharp decrease in the content of lactobacilli and a significant increase in the number of anaerobic, aerobic and microaerophilic microorganisms. Gardnerella vaginalis, Atopobium vaginae, Mobiluncus are found in bacterial vaginosis

spp.,
Prevotella
spp.,
Peptostreptococcus
spp.,
Mycoplasma hominis, Ureaplasma urealyticum
, etc. [19]. It has been established that in bacterial vaginosis, the pathological mechanism is associated with the formation of bacterial biofilms, which are colonies of microorganisms that attach to the vaginal epithelium and cover it completely or partially. Such biofilms often turn out to be resistant to antibacterial therapy, contribute to an increase in pH and displace endogenous lactoflora. It is known that lactobacilli can also form beneficial biofilms, produce surfactant, synthesize hydroxyl radicals that have antibacterial properties, in addition, lactobacilli are able to adhere to biofilms synthesized by pathogenic pathogens, and some types of lactobacilli contribute to the death of pathogenic biofilms.

Treatment of pregnant women with bacterial vaginosis presents certain difficulties, since its course is recurrent. Observations in recent years make us turn to probiotics as second-line therapy, which, as part of a complex of drugs, can represent one of the methods of treating patients with bacterial vaginosis, due to their ability to destroy biofilms created by pathogenic microorganisms, maintain vaginal pH within normal limits (no more than 4 ,5) and enable the formation of colonization resistance due to the lactobacilli included in their composition. The goal of treatment is not only to eradicate pathogenic microorganisms, but also, first of all, to ensure and long-term maintenance of normal microbiocenosis with the help of lactobacilli. Laktozhinal belongs to tribiotics and consists of three components: a combination of a prebiotic, a strain of Lactobacillus casei rhamnosus

spp.
35, presented in the form of a living culture, eubiotics (active metabolites) formed during the life of lactobacilli. Lactobacillus casei rhamnosus
spp.
35 [20, 21], by breaking down glycogen, they produce lactic acid, which reduces the pH of the vaginal contents, makes it possible to resist the proliferation of opportunistic microorganisms and helps maintain and restore normobiocenosis. The use of lactoginal promotes the formation of protective biofilms by lactobacilli, which creates an obstacle to the adhesion of pathogenic microorganisms. Thus, “bacterial competition” leads to the restoration of normal vaginal microflora. In addition, lactobacilli are capable of synthesizing hydrogen peroxide and other compounds that have bactericidal and bacteriostatic effects against pathogenic microbes. It has been established that Lactobacillus casei rhamnosus
spp.
35 have bactericidal activity against Gardnerella vaginalis, Prevotella bivia
, and certain strains of
Candida albicans
.

The purpose of our study is to study the comparative effectiveness of the use of lactoginal and ecofemin drugs as part of complex therapy for patients with bacterial vaginosis, as well as to evaluate the effectiveness of lactoginal monotherapy. Unlike the tribiotic lactoginal, ecofemin is presented as soluble vaginal capsules containing Lactobacillus acidofilus

108-109 CFU/ml, which are capable of producing hydrogen peroxide. This strain is isolated from the vaginal microflora of healthy women, using lactose as a medium.

One of the goals of the study was to compare the effectiveness of drugs containing different strains of lactobacilli in women of reproductive age. Particular attention was paid to studying the issue regarding long-term results of treatment and relapse prevention.

Material and methods

A total of 92 women aged 18 to 35 years with a confirmed diagnosis of bacterial vaginosis participated in the study. Patients randomly included in the study were divided into three groups. The presence of bacterial vaginosis at the time of inclusion in the study was confirmed by objective examination and laboratory methods using the criteria of R. Amsel et al. (1983), pH-metry (pH>4.5), detection of “key cells” in smears, data from a study of vaginal microbiocenosis using polymerase chain reaction (PCR) in real time (femoflora 16 analysis).

If pregnancy was detected at the time of participation in the study, as well as if STIs and vulvovaginal candidiasis were detected, patients could not continue to participate in the study.

The 1st group included 32 women who used 2% dalacin (clindamycin) cream intravaginally, after which they used ecofemin; the 2nd group included 30 patients who used dalacin in the form of a cream in the first stage and lactozhinal in the second stage of therapy, The 3rd (control) group consisted of 30 patients who received lactozhinal as monotherapy without the use of antibiotics.

In group 1, 2% dalacin cream was used intravaginally at 100 mg for 7 days, then ecofemin in the vagina, 1 capsule 2 times a day for 6 days.

In the 2nd group, treatment was carried out using dalacin in the form of a cream intravaginally, 100 mg for 7 days, then lactoginal capsules were used intravaginally, 1 capsule in the morning and evening for 7 days.

In the 3rd group, patients received the following treatment: in the morning and evening for 7 days, the vagina was douched with isotonic sodium chloride solution, and then Lactozhinal capsules were used, one 2 times a day, in the vagina for 7 days.

To assess the effectiveness of the drugs used, an analysis was carried out of the dynamics of complaints, objective examination data, pH-metry of the vaginal contents, microscopy of smears, the results of studying the composition of the vaginal microflora using real-time PCR (femoflor 16) immediately after treatment 1, 3, 6 months from the beginning treatment. The main baseline indicators were comparable in all three groups.

Results and discussion

Before treatment, the majority of patients in all groups complained of copious discharge with an unpleasant odor (in group 1 - 30 (93.75%) patients, in group 2 - 29 (96.66%), in group 3 - 29 (96.66%), noted itching and burning in the area of ​​the external genitalia in the 1st group - 5 (15.62%) women, in the 2nd - 4 (13.33%), in the 3rd - 5 (16.66%). Discomfort during sexual intercourse bothered 16 (50%) patients in group 1, 14 (46.66%) in group 2, and 15 (50%) in group 3. The patients were positive according to the criteria of R. Amsel et al. %), in the 3rd - in 28 (93.33%).Measurement of the pH of vaginal contents showed an increase in this indicator of more than 4.5 in all women (Table 1)

.

A real-time PCR study revealed a variety of gram-positive and gram-negative flora; there were no signs of inflammation in patients of all groups (Table 2)

.

Before treatment, in all groups a decrease in the number of lactobacilli was found to 102-103 CFU/ml; there was an increase in the number of Gardnerella vaginalis, Mobiluncus
spp.,
Atopobium vag., Candida alb
. By the beginning of the second day of treatment, all patients noted an improvement in their condition. By the end of the course of therapy, complaints disappeared, pH-metric indicators returned to normal in 100% of patients in all three groups. Immediately after the course of treatment, expectedly good results were obtained, but it seemed especially important to identify the duration of the therapeutic effect over 6 months and evaluate the treatment methods used, identifying the likelihood of relapse in each group.

As can be seen from table. 2

, despite the fact that during the initial analysis of lactobacilli, the normal amount in group 1 was almost 2 times higher (group 1 - 56.2%, group 2 - 23.3%, group 3 - 26.6% ), the treatment results in groups 2 and 3 were higher in terms of maintaining normal flora, and, very importantly, remained high as a result of a long-term 6-month follow-up.
In group 3, the fastest and most persistent growth of lactobacilli was noted (after 1 month - 93% of patients, after 6 months - 90%). The data is shown in the form of a histogram in Fig.
1 .

Figure 1. Growth of lactobacilli in patients of the examined groups before and after treatment.
Despite the equal initial number of patients with increased Gardnerella vag

.
in all groups, after 1 month from the start of therapy, the result in the 2nd and 3rd groups was significantly higher (1st group - 46.9%, 2nd - 60%, 3rd - 80%) and this the positive result persisted for 6 months (in the 1st and 2nd groups the indicators improved (see Fig. 1)
to 69 and 80%, respectively, and in the 3rd group this figure was 83%), which may provides relapse prevention.
Despite the fact that standard therapy includes antibiotic therapy or metronidazole, in some cases (intolerance, allergic reaction) antibiotics have to be abandoned. The results of the study indicate that in most cases, lactoginal therapy can be quite effective, especially in preventing relapses if the full course of treatment is followed (Fig. 2)
.

Figure 2. Growth of Gardnerella vaginalis in patients of the examined groups before and after treatment. It is quite possible that this is due to the in vitro confirmed fact of the production of Lactobacillus casei rhamnosus
spp. 35 bacteriocin Lactocin-160, which is active against a number of pathogenic microorganisms of the vaginal microflora. According to research [26], the bactericidal activity of lactocin is due to the disturbances it causes in the cell membranes of pathogenic microorganisms, probably due to the formation of pores leading to ATP leakage.

Despite the fact that during the initial study to identify Atopobium vag

.
Atopobium vag
is normal . in the 3rd group there was the least (13.3%) in contrast to patients in the 1st - 53.1% and 2nd - 23.3%, the highest result after 6 months was obtained in the 3rd group - 93%.

It should be noted that, in general, the results obtained on the influence of lactobacilli strains on Atopobium vag

.
requires a longer period of time compared to other pathogenic microorganisms (Fig. 3)
.
Figure 3. Growth of Atopobium vaginae in patients of the examined groups before and after treatment.
When analyzing the results of therapy in relation to the quantitative composition of Mobiluncus
(Fig. 4)
, we observed a situation similar to the number of
Gardnerella vag
.

Figure 4. Growth of Mobiluncus + Corynebacterium in patients of the examined groups before and after treatment. in all groups: 1 month after the start of therapy, the favorable result for identifying Mobiluncus
in groups 2 and 3 was significantly higher (group 1 - 50%, 2 - 63.3%, 3 - 90 %) and to varying degrees of severity, the therapeutic effect persisted for 6 months (group 1 - 71.9%, group 2 - 90%, group 3 - 90%)
(see Table 2)
, which can be considered as a better result in preventing relapses of bacterial vaginosis. This may be due to the fact that, according to modern research, the treatment of bacterial vaginosis requires a combination of lowering the pH of the vaginal environment and subsidizing lactobacilli to restore normal vaginal biocenosis. Considering that the waste products of lactobacilli are preserved in the vaginal capsules of Lactoginal, this may explain the higher treatment results in groups 2 and 3.

Of course, it should be noted that the results obtained can only be interpreted as a trend towards persistent cure, since no statistically significant differences were confirmed in any of the groups ( p

≥0.05). Nevertheless, the study can be considered as a pilot project, the purpose of which is to attract the attention of specialists to the development of new alternative treatment regimens for bacterial vaginosis. In the future, it may be possible to organize an in-depth study.

Thus, the results obtained can be interpreted as evidence that the use of probiotics in the treatment of patients with bacterial vaginosis significantly improves the results of therapy and contributes to the active normalization of vaginal microbiocenosis. In modern studies, it is very common to evaluate treatment results immediately after receiving therapy. We, first of all, set ourselves the task of tracking the long-term effect of the treatment and finding ways to minimize the possibility of relapses in the future. Taking into account the different activities of lactobacilli ( Lactobacillus acidophilus

and
Lactobacillus casei rhamnosus
spp.), the choice of one or another probiotic as part of the complex therapy of bacterial vaginosis should be determined based on the activity of lactobacilli included in the drug. Laktozhinal contains strains of lactobacilli that are able not only to adhere to the vaginal epithelium, maintaining the pH of the vaginal discharge, but also, according to a number of authors [24, 25], have a direct bactericidal effect on pathogenic microorganisms.

Thus, the possibility of prescribing lactoginal as monotherapy for bacterial vaginosis in women who cannot widely use antibiotics due to allergic reactions and other conditions seems very promising and requires further study.

conclusions

1. The results of the study indicate that the use of probiotics containing the Lactobacillus casei rhamnosus

, in the treatment of patients with bacterial vaginosis, significantly improves the results of therapy and contributes to the active normalization of vaginal microbiocenosis.

2. The choice of probiotic for use as part of complex therapy for patients with bacterial vaginosis should be determined by the activity of lactobacilli strains included in the drug.

3. Lactobacilli in the composition of lactoginal have a competitive inhibitory effect on a wide range of bacterial strains and can play an important role in maintaining the balance of the vaginal ecosystem.

4. The use of lactozhinal as monotherapy for bacterial vaginosis in women who cannot widely use antibiotics due to allergic reactions and other conditions seems very promising.