Gynecological smear “for flora”: what to look for and how to understand

Coccobacilli are a consequence of the occurrence of sexually transmitted infections in a woman or the development of bacterial vaginosis. Also, such bacteria may be present in the feces, which will soon lead to the appearance of dysbacteriosis.

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Coccobacilli - what is it?

The content of the article

Coccobacillary flora is the presence of a certain kind of bacteria, which are combined into 2 subspecies - bacilli and cocci. These include chlamydia and the causative agents of the disease - gardnerellosis. An imbalance in the flora of the genital organs occurs due to an increase in the number of coccobacilli. When this is associated with bacteria that are spread sexually, bacterial vaginosis develops, affecting hundreds of millions of women on earth. Cocci are beneficial microorganisms up to a certain point, but if the polymorphic flora is disturbed, the alkaline environment of the vagina increases, then the protection disappears and pathogenic bacteria begin to be active spread throughout the genitals, worsening the patient’s well-being. The appearance of cocci in a woman’s vagina can be caused by various factors, including:

• sexually transmitted infections;
• ignoring the rules of personal hygiene;
• weakening of the immune system;
• allergic reactions;
• long-term use of antibiotics;
• hormonal disorders;
• masturbation with dirty hands and so on.

The optimal ratio of coccobacillary flora in the female body. A control smear is taken at each scheduled visit to the gynecologist, or in the presence of painful symptoms of the reproductive system. Thanks to this analysis, the number of cocci bacilli in the discharge is determined. The resulting analyzes can be divided into 3 types:

1. In a slightly acidic environment, pH values ​​do not exceed 5.0.
2. Moderate value for a neutral environment – ​​pH 7.0.
3. An alkaline environment is characterized by pH values ​​greater than 7.5.

If the results obtained do not correspond to statistical data, then we are talking about the emergence of gram-positive cocci, which destroy the vaginal microflora and lead to deterioration of the patient’s reproductive system. When the mixed flora in the smear approaches alkaline in terms of indicators, then we can talk about the development of dysbacteriosis, due to advanced inflammation of the genital organs. Attention: multiplication of cocci is often a common cause of infertility, and therefore you should not delay a trip to the gynecologist (if specific discharge and pain in the ovarian area appear).

Preparing for a smear test

The optimal time for a smear on the flora is the middle of the cycle. During menstruation, biomaterial is not collected. This is due to the fact that the presence of blood cells can significantly distort its results.

Material for analysis can be taken from the urethra, from the vaginal walls or from the cervical canal. The preparatory measures for all three studies do not have any fundamental differences. At the consultation, the obstetrician-gynecologist will clarify whether antibiotics have been taken in the last two weeks before the appointment. If the answer is positive, the smear will be rescheduled for another time. The most reliable results can be obtained only by observing a number of conditions.

On the eve of the smear you should:

• for two to three days, eliminate the use of any vaginal suppositories;
• limit sexual intercourse in two to three days;
• the day before the test, do not take a bath (shower only);
• Avoid vaginal douching in two days;
• on the day of visiting the doctor, perform a standard toilet of the genitals with water;
• reschedule other gynecological examinations to another time (for example, colposcopy, ultrasound scanning with an intravaginal probe).

Additional diagnostics

If symptoms of dysfunction of the reproductive system appear (itching and burning in the vagina, copious dark-colored discharge with a specific odor, pain in the lower abdomen), it is important to immediately contact a gynecologist for examination and treatment of the disease. First of all, the woman’s microflora is checked, three control smears are made:

• vaginal vault;
• cervical canal;
• urethra.

Samples are applied to special glass and sent to the laboratory. The rods of coccal and bacillary flora have been carefully studied, and therefore there will be no problems with their identification. When identifying coccobacillary flora, additional research may require blood and urine. Only after conducting a comprehensive study will it be possible to determine the types of cocci and bacilli that inhabit the vaginal mucosa, as well as establish their number and the presence of concomitant diseases.

How long to wait for research results

In general, the time frame for a smear test for women is from one to four days. In this case, the day of the visit to the obstetrician-gynecologist is not taken into account. The duration of obtaining analysis results is determined by the specifics of the laboratory research method. The condition of the vagina, cervix and urethra is assessed within 24 hours. If the test results are unsatisfactory, the doctor may prescribe a PCR test*.

Advantages of the PCR method:

• reliability due to high sensitivity;
• speed of execution;
• specificity for STIs in any form;
• the ability to diagnose most infections of the urogenital tract;
• accuracy of determining the type of infectious agent.

Drugs used and treatment regimens for coccal and bacillary flora

The course of treatment consists of taking antibacterial agents, antibiotics, and immunomodulators. During pregnancy, medications are selected individually in order to avoid the negative impact of medicinal components on the developing organism. It is important to note that in the presence of coccobacillary infection, it is guaranteed that the woman’s sexual partner is infected, and therefore both of them need to be treated. To eliminate the disease, experts prescribe Metronidazole, together You can use gel and ointment with clindamycin. The effectiveness of such drugs is 95%, they are safer compared to tablet analogues. In some cases, to treat dysbiosis, it is enough to adjust the diet, introduce more plant products, fermented milk products with an average percentage of fat content into the diet. Probiotics can be prescribed as an adjuvant - “Linex” ", "Bifidumbacterin", "Lactobacterin", "Trilact". To improve the condition of the immune system, you need to take multivitamin complexes, eat more vegetables, berries and fruits. The list of folk remedies that can suppress the spread of pathogenic flora includes:

• Douching with herbal decoctions - chamomile, calendula, celandine. Perform the procedure for no more than 5-7 days; be sure to consult a doctor before starting the session.
• Vaginal suppositories with sea buckthorn oil and other essential extracts can be purchased at a pharmacy; the composition of the products is considered safe and has a positive effect on improving the functionality of the reproductive organs.
• Therapeutic tampons with sea buckthorn oil, honey, celandine can be prepared at home, however, before using them, it is important to have an informative conversation with your doctor.

To avoid relapse, it is necessary to pay more attention to the hygiene of the genital organs, to reconsider the means that can cause a violation of the acidity of the microflora. When having sexual intercourse, you need to use condoms, avoid casual sex, and undergo regular preventive examinations with a gynecologist. You should not self-medicate to avoid serious complications in a woman’s reproductive system. Coccobacillary flora does not always indicate serious diseases and pathological changes, so if any deviations from the norm are detected, you should not panic.

Bacterial vaginosis: new perspectives in treatment

A.A. KHRYANIN

, Doctor of Medical Sciences, Professor,
Novosibirsk State Medical University of the Ministry of Health of Russia; Vice-President of the ROO "Association of Obstetricians-Gynecologists and Dermatovenerologists", Novosibirsk, O.V.
RESHETNIKOV , MD, Senior Researcher,
Research Institute of Therapy and Preventive Medicine, Novosibirsk
Bacterial vaginosis is an infectious non-inflammatory syndrome characterized by the replacement of normal microflora (mainly lactobacilli) with polymicrobial associations of anaerobes and Gardnerella vaginalis. In recent years, the use of molecular biology techniques has shown that there is a much greater diversity of microorganisms associated with bacterial vaginosis than previously thought. Clindamycin has established itself as an effective and safe drug in the treatment of bacterial vaginosis in modern conditions.

The vaginal flora is a multicomponent microecological system that provides protection to all reproductive organs of women both under normal conditions and in pathology. The main representatives of the vaginal microflora are normally lactobacilli of various species (Lactobacillus spp.) and, to a lesser extent, bifidobacteria and corynebacteria, as well as anaerobic gram-negative bacilli of the genus Fusobacterium

and gram-negative cocci of the genus
Veillonella
. In healthy women of reproductive age, the leading place in the vaginal microcenosis is occupied by lactobacilli (anaerobic and aerobic origin), united under the general name “Dederlein's rods,” which make up more than 95% of the total vaginal microflora. Bifidobacteria, like lactobacilli, protect the vaginal mucosa from the effects of not only pathogenic, but also opportunistic microorganisms and their toxins, prevent the breakdown of secretory IgA, stimulate the formation of interferon and the production of lysozyme. In healthy women, anaerobic microflora prevails over aerobic microflora in a ratio of 10: 1 [1, 2].

Lactobacilli convert glycogen, which is contained in large quantities in the vaginal epithelial cells of women of reproductive age, into lactic acid, increasing the acidity of the vagina. In addition, lactobacilli produce hydrogen peroxide. As a result, the acidic environment of the vagina and hydrogen peroxide inhibit the growth of opportunistic microbes (staphylococci, streptococci, E. coli, anaerobic bacteria, Gardnerella vaginalis, Mobiluncus spp.

), which are found in small quantities in the vagina of the vast majority of women. If the proportion of lactobacilli decreases, their place in the ecosystem is taken by opportunistic microbes (primarily Gardnerella vaginalis). Thus, the acidic environment of vaginal contents, lactobacilli and the protective factors they produce form a powerful natural barrier to the penetration of pathogenic bacteria, protecting the upper parts of the woman’s reproductive tract.

A feature of the vaginal microflora is its variability under the influence of both exogenous (use of tampons, frequent vaginal showers and douching, change of sexual partner) and endogenous factors (neuroendocrine diseases, diabetes, hypothyroidism). Microcenosis is influenced by physiological and hormonal changes (puberty, pregnancy, menopause), phases of the menstrual cycle, and various disorders of menstrual function [3]. The use of certain medications (antibiotics, hormones) and surgical interventions also plays a role.

Bacterial vaginosis (BV) (formerly known as vaginal dysbiosis) is a general infectious non-inflammatory syndrome associated with vaginal dysbiosis and accompanied by an excessively high concentration of obligate and facultative anaerobic opportunistic microorganisms in combination with a sharp decrease in the number or absence of lactic acid bacteria in the vaginal discharge ( table 1

).

With bacterial vaginosis, elimination of lactobacilli occurs, accompanied by colonization of the vagina by anaerobes: Fusobacterium, Mobiluncus, Peptostreptococcus, Gardnerella vaginalis

. Despite the fact that BV is characterized by its polymicrobial nature, the main microorganism that triggers the process is Gardnerella vaginalis, a facultative anaerobic gram-negative rod; It is this that determines the main symptoms of BV.

The fact is that G. vaginalis

has the unique ability to form a so-called biofilm on the surface of the urogenital mucosa.
Biofilm a
conglomerate of microorganisms located on any surface, the cells of which are attached to each other. Typically, cells are immersed in an extracellular polymeric substance (extracellular matrix) they secrete - mucus. It is believed that 95-99% of all microorganisms in the natural environment exist in the form of biofilm. Microorganisms form a biofilm under the influence of a number of factors, including cellular recognition of sites of attachment to the surface and the presence of nutrients or aggressive substances, oxygen, etc. In the biofilm formation mode, the cell changes its behavior, which is determined by the regulation of gene expression.

It is this biofilm, like cement or glue, that attracts other microorganisms to itself, forming a conglomerate of bacteria, most of which have a pathogenic, or at least dangerous, effect for humans. Biofilms have been found to consist primarily of Gardnerella vaginalis

, while
Atopobium vaginae
was present in 80% of cases and constituted 40% of the biofilm mass.
Other bacteria are much less common, including bacteria belonging to the genera Bacteroides, Corynebacterium, Lactobacillus, Veillonella, Ruminococcus and Streptococcus
[4].

Factors contributing to the development of BV include:

— Immunodeficiency states of the body (chronic stress, diseases, massive treatment with antibiotics and cytostatics, radiation therapy, diabetes, vitamin deficiency). — Hormonal dysfunction of the ovaries, including age-related hormonal changes, hormone therapy. — Inhibition of local immunity factors and lactobacilli (vaginal douching, foreign bodies, intrauterine contraceptives, use of spermicides, contraceptive suppositories and creams containing 9-nonoxynol (Patentex Oval, Nonoxynol) — Massive infection of the vagina, promiscuous relationships.

Prevalence of BV

It is not possible to determine the true incidence of BV due to the fact that in 1/3 of women this disease is asymptomatic. The few studies have found the prevalence of BV to range from 3.14% in asymptomatic women aged 18 to 72 years (screened in the Netherlands) to 49% in women aged 13 to 65 years in a colposcopy office in the United States. The wide variation in reported prevalence rates may be due to the inclusion of different patient groups, demographic variations, and different diagnostic criteria. Overall, based on the results of 21 studies, the overall prevalence of BV was 27.1%, with no significant difference between developed (28.0%) and developing (23.5%) countries [5].

During the Human Microbiome Project, molecular biology techniques revealed that there is a much greater diversity of microorganisms associated with BV than was apparent using culture methods. As an example, here is a list of microorganisms previously unknown in BV: Atopobium vaginae, BV-associated bacteria (BVAB-1, BVAB-2 and BVAB-3) from the order Clostridiales, Megasphaera spp, Leptotrichia spp, Dialister spp, Chloroflexi spp, Olsenella spp, Streptobacillus spp, Shuttleworthia spp, Porphyromonas asaccharolytica

[6].

These diverse organisms accumulate to form distinct communities or profiles, which suggest that BV is not a single entity but a syndrome of variable composition, causing a variety of symptoms, different phenotypic outcomes, and resulting in variable responses to different antibiotic regimens. Some organisms or combinations of organisms are highly specific for BV, so in the future the use of molecular quantitative assays will allow better diagnosis of each BV subtype and individualized therapy. A woman's race and geographic region, as well as different racial groups within the same geographic region, have significant differences in which microorganism is dominant in the vaginal environment. In most populations, L. crispatus is the dominant isolate, and in white women, L. crispatus and/or L. jensenii are more common than any other Lactobacillus

[6].

Among African American women in the United States, the prevalence of gram-negative bacteria BVAB1, which was previously mistakenly perceived as Mobiluncus spp,

. [7].

A recent meta-analysis involving more than 10,000 women demonstrated an association between BV and precancerous conditions, namely cervical intraepithelial neoplasia/dysplasia [5]. Since only a minority of patients infected with HPV develop cervical dysplasia, studies of cervical carcinogenesis should include the presence of an additional contributing factor. This factor is BV. Biochemical changes in the vaginal secretions of women with BV include the formation of metabolic products such as propionate and butyrate, which can damage epithelial cells. In addition, BV-associated anaerobes release volatile amines (especially putrescine, trimethylamine and cadaverine), which appear in the vaginal environment after the conversion of amino acids derived from the abundance of anaerobes, and form, in combination with nitrites (derived from bacterial nitrates), nitrosamines. These carcinogenic compounds are capable of forming DNA adducts and therefore mutagenic events. Local accumulation of nitrosamines during episodes of BV may promote cellular transformation in the cervical epithelium in combination with other oncogenic agents such as HPV infection. In addition, patients with BV and dysplasia showed an altered profile of local cervical immunity, namely nitric oxide (NO) and cytokine concentrations (IL-6, IL-8 and IL-10). Finally, another important additional cofactor in cervical carcinogenesis may be the relative absence of hydrogen peroxide (H2O2), normally produced by lactobacilli. This prevents the selective induction of apoptosis, which is a key element of lactobacilli-stimulated antitumor defense [5].

In non-pregnant women, the presence of BV is associated with an increased risk of infection of the upper genital tract with non-sexual infections and STIs, as well as HIV infection. During pregnancy, BV increases the risk of post-abortion sepsis, early miscarriage, recurrent miscarriage, late miscarriage, premature rupture of membranes, spontaneous preterm contractions and preterm birth, histological chorioamnionitis and postpartum endometritis. As a result, abnormal vaginal flora may predispose to increased colonization of the genital tract, infiltration of membranes, microbial invasion of the amniotic cavity, and fetal damage [6].

Careful observation of 49 women (vaginal samples taken weekly during pregnancy and monthly after childbirth) showed that a relatively greater diversity of microorganisms present in the birth canal was associated with the risk of preterm birth, and the highest risk was found in women whose vaginal secretions contained few lactobacilli , as well as microorganisms of the species Gardnerella spp

and
Ureaplasma spp.
Most women have postpartum disturbances in the vaginal microbiota with a decrease in
Lactobacillus spp
and an increase in various anaerobes, such as
Peptoniphilus, Prevotella and Anaerococcus
species. This impairment was not associated with gestational age at delivery and persisted for up to 1 year postpartum. The findings have important implications for predicting preterm birth and for understanding the potential impact of persistent changes in the postpartum microbiota on maternal health, including outcomes in subsequent short-term pregnancies [8].

Laboratory diagnosis of BV

BV can be diagnosed clinically or using a set of clinical criteria, microscopic, enzymological, chromatographic methods, as well as using qualitative or semi-quantitative cultural methods [6].

In world medical practice, clinical and laboratory criteria proposed by Amsel R. (1983) are used, listed in Table 2 [9]. The diagnosis of bacterial vaginosis is considered confirmed if three or four of the following criteria are present:

The presence of at least 3 positive signs out of 4 is considered diagnostically significant:
1. Clinical manifestations. 2. Increased pH of vaginal discharge > 4.5. 3. Positive amine test (increased smell of rotten fish when reacting with 10% KOH). 4. Gram smear microscopy criteria: desquamated epithelium in large quantities, “key cells” make up 20% of all epithelial cells, leukocytes are rare.

The culture method has the highest sensitivity and specificity in the diagnosis of bacterial vaginosis.
Its high information content is due to qualitative and quantitative indicators of the composition of the vaginal microbiocenosis. Accordingly, with bacterial vaginosis, there is a decrease in the number of lactobacilli and an increase in the content of opportunistic flora. Disadvantages of the method: relative high cost and duration of implementation. The study of Gardnerella DNA in scrapings from lesion sites using PCR is an important additional criterion for BV. Expanded criteria for diagnosing BV
1. Predominance of epithelial cells over leukocytes (no more than 30 per field of view). 2. No visual signs of inflammation. 3. The presence of at least 20% key cells. 4. Detection of less than 5 lactobacilli per field of view by immersion microscopy. 5. Polymicrobial picture of the smear (abundant polymicrobial coccal and rod G-/G+ flora. 6. Increased bacterial contamination in the cytological preparation.

Nugent criteria

The low sensitivity of the Amsel criteria and the presence of asymptomatic forms of bacterial vaginosis forced us to look for other methods and criteria for confirming the diagnosis. At the end of the 80s. Spiegel proposed using a scoring system for diagnosing bacterial vaginosis, taking into account the ratio of morphotypes of lactobacilli and vaginal gardnerella during microscopy of a Gram-stained vaginal smear. However, the system did not take root, and only in 1991 Nugent RP et al. proposed their laboratory criteria for diagnosing bacterial vaginosis (Nugent's Diagnostic Criteria for Bacterial Vaginosis), which are still widely used in world medicine [10]. It is based on a system of points (points) from 0 to 7 and their combination for diagnosing and assessing the degree of bacterial vaginosis by assessing three bacterial morphotypes of the vagina ( Table 3

):

A - Lactobacilli - large gram-positive rods ( Lactobacillus acidophilus: large gram-positive rods)

B - Gardnerella vaginalis and Bacteroides species:small gram-variable or
gram-negative
C -
Mobiluncus species:curved gram-variable
rods

A recent study compared the Amsel and Nugent criteria; as a result, it turned out that the Amsel criteria are somewhat less informative, but can be used in the absence of a specialized laboratory [11].

In recent years, the global scientific community has developed criteria for the differential clinical and laboratory diagnosis of BV and other similar or associated conditions (diseases). There are nonspecific manifestations that can be recorded by a gynecologist, followed by more accurate laboratory analysis (Table 4) [12].

Treatment
Recognition of the importance of BV and its association with STIs and poor reproductive prognosis has led to the search for better and more comprehensive treatment options. There is a wide range of differential diagnosis for vaginal discharge, and the success of treatment often depends on the correct diagnosis, however, a large percentage of patients are treated without additional specific tests.

The presence of a wide range of therapeutic options diagnosing the main causes of vaginitis, and the lack of a clear diagnosis in 30% of patients, even after additional expensive examination, explains why many gynecologists use these drugs. Misdiagnosis or failure to diagnose other infections, associated mainly in cases of BV and T. vaginalis

, can lead to inadequate treatment, a new exacerbation and re-infection.

In non-pregnant women, treatment will not only eliminate vaginal discharge, but will also reduce the likelihood of infectious complications after an abortion and/or hysterectomy is possible for each woman. In addition, treatment of BV by restoring the acidic pH in the vagina reduces the risk of infection with the immunodeficiency virus and other sexually transmitted diseases.

In pregnant women, treatment with BV, along with the above-mentioned effects, helps reduce the risk of developing pregnancy complications, namely premature rupture of amniotic fluid, the onset of labor (contractions) and childbirth itself, as well as postpartum inflammation of the inner surface of the uterus (endometritis). Pregnant women with asymptomatic BV should also be treated, especially if there is a threat of premature birth.

The drug of choice for the treatment of BV is clindamycin.

This is an antibiotic of the lincosamide group for topical use in gynecology. The mechanism of action of the drug is associated with a disruption of intracellular protein synthesis in the microbial cell at the level of the 50S ribosomal subunit. It has a bacteriostatic effect, and in higher concentrations it has a bactericidal effect against some microorganisms. Has a wide spectrum of action. Active against microorganisms that cause bacterial vaginosis:

•
Gardnerella vaginalis. • Mobiluncus spp. • Bacteroides spp. • Mycoplasma hominis. • Peptostreptococcus spp.
Clindamycin (Dalacin)

.
Release form: vaginal cream and vaginal suppositories
. 5 g of cream (1 dose) vaginal 2% and one vaginal suppository contain: clindamycin phosphate 100 mg.

Pharmacokinetics.

After a single intravaginal administration of 100 mg of clindamycin, an average of 4% of the administered dose is systemically absorbed. Cmax in blood plasma averages 20 ng/ml.

Clinical studies on the use of clindamycin in women in the first trimester of pregnancy have not been conducted, therefore the use of Clindacin in the first trimester of pregnancy is possible only when the expected benefit to the mother outweighs the risk to the fetus. Use in the second and third trimesters of pregnancy is possible if the expected effect of therapy outweighs the potential risk to the fetus (adequate and strictly controlled studies have not been conducted in pregnant women; clindamycin passes through the placenta and can concentrate in the fetal liver, but no complications have been reported in humans). Studies have not determined whether treating bacterial vaginosis reduces the risk of adverse pregnancy outcomes such as premature rupture of membranes, preterm labor, or preterm delivery. FDA category of effect on the fetus is B.

A study conducted in Switzerland examined 5,377 pregnant women with symptoms of potential obstetric complications at 25–37 weeks' gestation. pregnancy. Symptomatic women were tested by culture for Mycoplasma hominis and Ureaplasma spp. and treated with clindamycin if positive. As a result of treatment, the percentage of premature births and respiratory complications in newborns significantly decreased [13].

Our colleagues from Belgium searched the PubMed and Web of Science databases to find new approaches in the prevention, treatment and prevention of relapses of BV. As a result, it turned out that clindamycin and metronidazole remain the main drugs in the treatment of BV. Other medications such as tinidazole, rifaximin, nitrofuran, decalinum chloride, ascorbic acid (vitamin C) and lactic acid are being intensively studied. It is believed that the use of a combination regimen, alternating and long-term administration to prevent relapses is promising. The benefits of parallel administration of probiotics are also undoubted [14].

A multicenter, randomized, double-blind study conducted in Germany, Austria, and Switzerland compared the effectiveness and tolerability of 2% vaginal clindamycin cream (5 g at night for 7 days) and oral metronidazole (500 mg orally for 7 days) in the management of BV. Patients were observed 5-10 days and 25-39 days after completion of treatment. As a result, cure or improvement was noted after 1 month in 83% of patients in the clindamycin group versus 73% in the metronidazole group, side effects were noted with equal frequency (12%) in both groups [15].

Recently, the concept of aerobic vaginitis has appeared in the world literature. Aerobic vaginitis is an inflammatory disease of the vagina caused by aerobic microflora with a sharp decrease or absence of normal vaginal lactoflora. Previously, the term “aerobic vaginitis” meant bacterial vaginitis. The basis of aerobic vaginitis, as with bacterial vaginosis, is the reduction or absence of normal vaginal lactoflora and its replacement with aerobic bacteria. The exact causes and mechanism of development of aerobic vaginitis are still unknown. It is also unknown why in some cases there is a proliferation of anaerobic microflora and the development of bacterial vaginosis, and in others the colonization of the vagina by aerobic microorganisms and the development of aerobic vaginitis. The most common etiological agents of aerobic vaginitis ( Escherichia coli, Enterococcus sp.

, group A beta-hemolytic streptococcus, Staphylococcus aureus).
In resolving this controversy, it turned out that vaginal suppositories containing kanamycin or clindamycin showed high effectiveness in relieving aerobic vaginitis in non-pregnant women. Additionally, clindamycin (vaginal suppositories) in combination with probiotics was found to be a better choice for pregnant women with aerobic vaginitis than metronidazole [16]. Conclusion
Bacterial vaginosis is a long-known pathological condition of the female genital area with well-developed clinical diagnostic criteria (Amsela and Nugenta).
New molecular diagnostic capabilities are constantly expanding our understanding of the various types of native and foreign microflora, indicating the diversity of the vaginal microbiota in each individual woman. In this case, the choice of the optimal drug provides clinical effectiveness against most pathogenic microorganisms. Such a drug can be clindamycin, the significance of which in the treatment of bacterial vaginosis is beyond doubt in recent scientific publications. References
1. Anderson MR, Klink K, Cohrssen A. Evaluation of vaginal complaints. JAMA 2004, 291:11:1368–1379. 2. Mitchell H. Vaginal discharge – causes, diagnosis, and treatment. BMJ 2004, 328:7451:1306–1308. 3. Khryanin A.A., Reshetnikov O.V. Bacterial vaginosis: new ideas about the microbial biosocium and treatment possibilities. Medical Council, 2014, 17: 128-133. 4. Verstraelen H, Swidsinski A. The biofilm in bacterial vaginosis: implications for epidemiology, diagnosis and treatment. Curr Opin Infect Dis 2013, 26: 86–89. 5. Gillet E, Meys JFA, Verstraelen H et al. Association between bacterial vaginosis and cervical intraepithelial neoplasia: Systematic review and meta-analysis. Plos One, 2012, 7, Issue 10 e45201. 6. Lamont RF, Sobel JD, Akins RA et al. The vaginal microbiome: New information about genital tract flora using molecular based techniques BJOG, 2011, 118(5): 533–549. 7. Muzny CA, Sunesara IR, Griswold ME et al. Association between BVAB1 and high Nugent scores among women with bacterial vaginosis. Diagn Microbiol Infect Dis., 2014 December, 80(4): 321–323. 8. Di Giulio DB, Callahan BJ, McMurdie PJ et al. Temporal and spatial variation of the human microbiota during pregnancy Proceedings of the National Academy of Sciences 2015/ www.pnas.org/cgi/doi/10.1073/pnas.1502875112. 9. Amsel R, Totten PA, Spiegel CA, et al. Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiologic associations. Am J Med 1983, 74(1): 14–22. 10. Nugent RP, Krohn MA, Hillier SL. Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation. J Clin Microbiol, 1991, 29(2): 297–301. 11. Mohammadzadeh F, Dolatian M, Jorjani M, Alavi Majd H. Diagnostic value of Amsel's clinical criteria for diagnosis of bacterial vaginosis. Glob J Health Sci., 2014 Oct 29, 7(3): 8-14. 12. Workowski K.A. Sexually transmitted diseases treatment guidelines, 2010. MMWR Recommend Rep 2010; 59:61–63. 13. Vouga M, Greub G, Prodhom G, et al. Treatment of genital mycoplasma in colonized pregnant women in late pregnancy is associated with a lower rate of premature labor and neonatal complications. Clin Microbiol Infect, 2014 Oct, 20(10): 1074-9. 14. Donders GG, Zodzika J, Rezeberga D. Treatment of bacterial vaginosis: what we have and what we miss. Expert Opin Pharmacother, 2014 Apr, 15(5): 645-57. 15. Fischbach F, Petersen EE, Weissenbacher ER, et al. Efficacy of clindamycin vaginal cream versus oral metronidazole in the treatment of bacterial vaginosis. Obstet Gynecol, 1993 Sep, 82(3): 405-10. 16. Han C, Wu W, Fan A, Wang Y, Zhang H, Chu Z, Wang C, Xue F. Diagnostic and therapeutic advancements for aerobic vaginitis. Arch Gynecol Obstet, 2015 Feb, 291(2): 251-7.

Bibliography

1. Gynecology textbook. IV edition ed. Academician of the Russian Academy of Medical Sciences, Professor G.M. Savelyeva; prof. V.G. Breusenko 2012
2. Urogenital candidiasis. Clinical recommendations. Moscow, 2016 – 22 p.
3. Vulvovaginal candidiasis: pathogenesis, diagnosis and treatment tactics. Bayramova G.R., Amirkhanyan A.S., Chernova V.F. //Doctor.Ru 2018. No. 10 (154). pp. 32-36
4. Sherry L., Kean R., McKloud E., O'Donnell LE, Metcalfe R., Jones BL et al. Biofilms formed by isolates from recurrent vulvovaginal candidiasis patients are heterogeneous and insensitive to fluconazole. Antimicrob. Agents. Chemother. 2017; 61(9): e01065-17
5. Prilepskaya V.N. Vulvovaginal candidiasis. Clinic, diagnosis, principles of therapy: manual / V.N. Prilepskaya, G.R. Bayramova - M 2008 - 50s
6. Atlas of pathogens of fungal infections/E.N. Moskvitina and others - Moscow GEOTAR-Media, 2021 208p
7. Zordan R., Cormack B. Adgesis on opportunistic fungal pathogens In: Calderone RA, Clancy CJ, ed Candada and candidiasis/ Washington: ASM press; 2012: 243-259)
8. Zhang Y., Li W., Chu M., Chen H., Yu H., Fang C. et al. The AAA AT Pase Vps4 plays important roles in Candida albicans hyphal formation and is inhibited by DBeQ. Mycopathology 2016; (5-6) 329-39
9. Murciano C., Moyes DL, Runglall M., Yobouti P., Islam A., Hoyer LL et al. Evaluation of the role of Candida albicans agglutinin-like sequence (Als) proteins in human oral epithelial cell interactions. Plos one 2012.
10. Center for Disease Control (CDC) Sexually Transmitted Disease Treatment Guidelines, 2015.
11. Donders GG, Bellen G., Mendling W. Management of recurrent vulvovaginal candidosis as a chronic illness. Gynecol. Obstet. Invest 2010 70(4):306-21
12. Ankirskaya A.S. Muravyova V.V. Microbiological characteristics of vaginal infections caused by fungi of the genus Candida // sexually transmitted diseases 2001. pp. 12-14
13. Eschenbach DA Chronic vulvovaginal candidosis N Engl. J Med 2004; 351(9)
14. Tikhomirov A.L. Oleinik Ch.G. Optimization of treatment of recurrent vulvovaginal candidiasis // effective therapy in obstetrics and gynecology. 2007 No. 3 from 22-27
15. Bayramova G.R. Recurrent vaginal candidiasis. Clinic, diagnosis, treatment. dis. Doctor of Medical Sciences M. 2013 (46s)
16. Prilepskaya V.N. Bayramova G.R. Vulvovaginal candidiasis, modern ways to solve the problem. Difficult patient 2006 (from 33-36)