According to modern concepts, bacterial vaginosis is an infectious non-inflammatory syndrome of polymicrobial etiology, associated with dysbiosis of the vaginal biotope and characterized by a quantitative increase in obligate and facultative anaerobic opportunistic microorganisms and a decrease or complete disappearance of lactobacilli, especially those producing peroxide. The etiological spectrum of bacterial vaginosis is represented by microaerophilic, obligate anaerobic gram-positive and gram-negative bacteria ( Gardnerella vaginalis, Atopobium vaginae , Mobiluncus
spp,
Peptostreptococcus
spp.
, Prevotella
spp
., Bacteroides
spp. and etc.). As a rule, in laboratory studies it is possible to identify associations of various microorganisms that interact according to the principle of symbiosis [1].
According to epidemiological studies [2], bacterial vaginosis is one of the most common infectious diseases of the vagina, and the frequency of its detection varies from 12 to 80% and depends on the population of women examined.
Clinically, bacterial vaginosis is manifested by the presence of homogeneous discharge from the genital tract, often with an unpleasant odor, which significantly reduces the quality of life of patients. Symptoms of the disease also include the following: discomfort in the external genital area, pain during sexual intercourse (dyspareunia), and less commonly, itching and/or burning in the genital area.
Bacterial vaginosis is detected mainly in women of reproductive age. The disease does not pose an immediate threat to a woman’s life, but is a risk factor for the development of pregnancy complications: spontaneous abortion, intra-amniotic infection, premature rupture of amniotic fluid, premature birth. Also, bacterial vaginosis can potentiate the development of postoperative infectious complications, inflammatory diseases of the pelvic organs, peritonitis, abscesses of the pelvic organs with the introduction of intrauterine contraceptives. The long course of the disease is one of the risk factors for the development of cervical neoplasia, and also increases susceptibility to sexually transmitted infections (STIs), especially HIV infection and genital herpes [3, 4].
According to modern domestic and foreign recommendations, drugs from the 5-nitroimidazoles (5-NIMZ) group and clindamycin are used in the treatment of bacterial vaginosis [5, 6]. 5-NIMZ derivatives are drugs with a bactericidal action and selective activity against infectious agents. The targets of 5-NIMZ action in microbial cells are DNA, RNA and cellular proteins. Of all the representatives of the 5-NIMZ group, metronidazole, ornidazole and tinidazole are currently widely used.
Metronidazole is the most commonly used drug in the 5-NIMZ group in the treatment of infectious diseases. However, in recent years, studies have appeared demonstrating a decrease in the sensitivity of the etiological agents of urogenital trichomoniasis and bacterial vaginosis to metronidazole, which does not allow achieving the desired effectiveness of therapy. Numerous side effects are also known when using this drug, especially from the gastrointestinal tract.
Despite the possible cross-resistance of infectious agents to nitroimidazoles, the problem of their resistance to metronidazole can be most effectively solved by using other drugs of this group, for example, ornidazole. It should be taken into account that the effectiveness of therapy largely depends on the quality of the prescribed drug. One of the most important characteristics that determines the identity of pharmaceutically equivalent drugs according to the main pharmacokinetic parameters in vivo
, is bioequivalence. In this case, drugs are equivalent if they provide the same bioavailability of the drug substance. Most original drugs (as opposed to generics) are manufactured in accordance with GMP standards and, in addition to pharmacokinetic studies under various conditions, undergo extended clinical studies up to phase IV.
Tiberal is an original high-quality preparation of ornidazole, which has confirmed a high profile of efficacy and safety of use in numerous studies on the treatment of patients with bacterial vaginosis [7-9]. Tiberal, like other drugs of the 5-NIMZ group, is active against gram-negative and gram-positive anaerobic bacteria and protozoa. However, when developing the drug, the already known disadvantages of metronidazole were initially taken into account, which made it possible to improve its pharmacological properties. Thus, after taking Tiberal, the effective concentration in the blood is maintained much longer, which is associated with the half-life of the drug, which is 13-14 hours (for metronidazole - 8.5 hours), and the maximum concentration of Tiberal in the blood is observed already 3 hours after its oral administration administration, while less than 15% of the drug is bound to plasma proteins (metronidazole - more than 20%).
The purpose of the study was to study the effectiveness, safety and tolerability of the use of tiberal (ornidazole) tablets in the treatment of patients with bacterial vaginosis in comparison with the effectiveness of therapy with trichopolum (metronidazole) in the same form.
Pharmacological properties of the drug Tinidazole
Tinidazole is active against both protozoa and most anaerobic microorganisms. The following are sensitive to tinidazole: Trichomonas vaginalis, Entamoeba histolytica, Giardia intestinalis, Bacteroides spp., Clostridium spp., Eubacterium spp., Fusobacterium spp., Gardnerella spp., Peptococcus spp., Peptostreptococcus spp. After oral administration, tinidazole is rapidly and completely absorbed. With intravenous administration, the maximum concentration in the blood plasma is achieved 1 hour after the end of the infusion; after 6 hours, the content of tinidazole in the blood serum is 2 times higher than the MIC for anaerobes. Binding to plasma proteins is insignificant; the content of active tinidazole is 88%. Tinidazole penetrates well into body tissues and areas of inflammation. At comparable plasma concentrations, tinidazole penetrates into the CSF better than metronidazole (88 and 43%, respectively). In the peritoneal fluid, fallopian tubes, endometrium, myometrium, cervical canal, vaginal secretions and skin, the concentration of tinidazole is almost equal to its concentration in the blood plasma and exceeds the MIC. 20–25% of tinidazole is excreted in the urine during the day; Tinidazole passes into breast milk in large quantities.
results
The main subjective manifestations of bacterial vaginosis in the examined women were pathological discharge of a creamy homogeneous nature from the genital tract, which was observed in 30 (100.0%) patients of the 1st group and in 29 (96.7%) patients of the 2nd group. Also, patients of the 1st and 2nd groups complained of an unpleasant “fishy” smell of discharge from the genital tract - 28 (93.3%) and 27 (90.0%), respectively, discomfort in the genital area - 16 (53, 3%) and 14 (46.7%) patients, respectively, and pain during sexual intercourse - 10 (33.3%) and 11 (36.7%) patients, respectively.
In all examined patients, microscopic examination of the vaginal contents revealed “key cells.” A positive amino test result was determined in 29 (96.7%) patients of the 1st group and in 30 (100%) of the 2nd group. Also, most patients showed an increased pH value of the vaginal contents - more than 4.5. Both groups were comparable in terms of clinical signs of bacterial vaginosis (Fig. 1).
Rice. 1. Results of clinical examination of patients before prescribing therapy (p>0.05).
The average severity of pathological discharge according to patients of the 1st group was 2.4, according to patients of the 2nd group - 2.2; unpleasant odor of discharge from the genital tract - 1.7 and 1.7; discomfort in the genital area - 1.2 and 0.8; pain during sexual intercourse – 0.6 and 0.6, respectively. According to the results of an objective examination, the average severity of pathological discharge in patients of the 1st group was 2.3, in patients of the 2nd group - 2.2.
When analyzing the qualitative composition of vaginal microflora, the following results were obtained :
A. vaginae
was identified in 12 (40.0%) patients of group 1 and 16 (53.3%) of group 2
, G. vaginalis
- in 28 (93.3%) and 29 (96.7%) patients, respectively.
Other microorganisms associated with bacterial vaginosis were also identified: Mobiluncus , Leptotrix
(Fig. 2).
Rice.
2. Results of laboratory tests of patients before prescribing therapy. According to the bacteriological study, the majority of the examined patients (83.3% of patients of the 1st group and 80.0% of the 2nd group) had representatives of the Lactobacillaceae
were not determined, in 3 (10%) and 3 (10%) patients of the study groups, respectively, the number of lactobacilli was at the level of 102-103 CFU/ml, and in 2 (6.7%) and 3 (10%) patients, respectively - at the level of 104-105 CFU/ml (Fig. 3).
Rice.
3. Results of assessing the lactobacillary component of the vaginal microflora before prescribing therapy in patients of the examined groups. After establishing that the clinical and laboratory data of the examined patients met the criteria for inclusion in the study, all patients were prescribed therapy according to the regimens given in the “Material and Methods” section.
14 days after the end of therapy, subjective and objective clinical indicators were assessed, and laboratory tests were performed.
According to the results of a survey of patients, it was found that 1 (3.3%) patient of the 1st group and 5 (16.6%) patients of the 2nd group complained of discharge from the genital tract. Also, 1 (3.3%) patient of the 1st group and 4 (13.3%) patients of the 2nd group complained of an unpleasant “fishy” smell of pathological discharge. Discomfort in the genital area bothered 4 (13.3%) patients of the 2nd group, pain during sexual intercourse was noted by 1 (3.3%) patient of the 2nd group.
When assessing the nature of vaginal discharge, the following data were obtained: in 1 (3.3%) patient of the 1st group and 4 (13.3%) of the 2nd group, the vaginal discharge had a creamy character and an unpleasant “fishy” odor, characteristic of a bacterial vaginosis; in 1 (3.3%) patient of group 2, vaginal discharge was cheesy and accompanied by hyperemia and swelling of the vaginal mucosa. A positive amino test result was determined in 4 (13.3%) patients of the 2nd group, a vaginal pH value of more than 4.5 - in 1 (3.3%) patient of the 1st group and 3 (13.3%) of the 2nd group. th group. Microscopic examination of the vaginal contents in 1 (3.3%) patient of the 1st group and 4 (13.3%) of the 2nd group revealed “key” cells, which also confirmed the diagnosis of bacterial vaginosis in the examined women (Fig. 4 ).
Rice. 4. Results of clinical examination of patients after therapy (p<0.05).
The severity of pathological discharge according to the patient of the 1st group was 2.0, according to the patients of the 2nd group - 2.2; unpleasant odor of discharge from the genital tract - 1.0 and 1.6, respectively; discomfort in the genital area - 0 and 1.6, respectively; pain during sexual intercourse - 0 and 1.0, respectively. According to the results of an objective examination, the severity of pathological discharge in the patient of the 1st group was 2.0, in the patients of the 2nd group - 2.2.
A qualitative assessment of the vaginal microflora revealed that
A. vaginae
and
Mobiluncus
were identified in the vaginal contents only in patients of group 2 in 3 (10.0%) and 2 (6.7%) subjects, respectively.
G. _ vaginalis
were detected in 1 (3.3%) patient of group 1 and 2 (6.7%) patients of group 2 (Fig. 5).
Rice.
5. Results of bacterioscopic examination of vaginal contents in patients of the examined groups after therapy (p<0.05). When assessing the lactobacillary component of the vaginal microflora after therapy, it was found that normalization of indicators (the number of lactobacilli at the level of 105-107 CFU/ml) was achieved in 21 (70.0%) patients of group 1 and in 14 (46.7% ) patients of group 2. It was noteworthy that 10 (33.3%) patients of group 2 had representatives of the Lactobacillaceae
were not determined; in group 1 this figure was 10% (Fig. 6).
Rice.
6. Results of assessment of the lactobacillary component of the vaginal microflora in patients of the examined groups after therapy (p<0.05). There was no significant difference in the ease of use of the drugs. However, when analyzing adverse drug events, it was revealed that 6 (20.0%) patients of group 2 experienced side effects from the gastrointestinal tract (nausea, metallic taste in the mouth, pain in the epigastric region, diarrhea) during treatment with metronidazole ). In 1 (3.3%) patient of group 1, discomfort in the epigastric region was recorded during treatment, which resolved spontaneously after completion of therapy.
When monitoring vital signs, no clinically significant deviations were identified in any of the examined patients.
Use of the drug Tinidazole
Tablets are taken during or after meals. For trichomoniasis and giardiasis - 2 g once. For amoebic dysentery (acute form) - 2 g once a day for 3 days. In the case of amoebic liver abscess - individually, depending on the activity of the process. Treatment begins at a dose of 1.5–2 g per day for 3 days; in the absence of clinical improvement, treatment is continued for another 2 days. Children with acute intestinal amebiasis - 30–60 mg/kg orally once a day for 3 days. For amoebic liver abscess - 50-60 mg/kg orally per day for 5 days.
Discussion
According to the data obtained, clinical signs of bacterial vaginosis after treatment were significantly more often recorded in patients of group 2 compared with those in patients of group 1: in 4 (13.3%) and 1 (3.3%) patients, respectively . In 1 (3.3%) patient of the 2nd group, in addition, clinical signs of vulvovaginal candidiasis were identified.
Normalization of lactobacillary microflora indicators was established in 83.3% of patients in group 1, which significantly exceeded these indicators in patients in group 2 (56.7%). At the same time, the absence of representatives of the Lactobacillus
in laboratory studies, it was observed in 10 (33.3%) patients treated with Trichopolum (metronidazole), and only in 3 (10.0%) patients treated with Tiberal (ornidazole). However, the results obtained may be a consequence of the patient sample and dictate the need for further research to study the effect of drugs on the lactobacillary microflora of the vagina.
Against the background of the therapy, it was possible to achieve a decrease in the intensity of the average severity of pathological discharge (as assessed by patients) by 16.7% in patients of the 1st group, while there was no dynamics in patients of the 2nd group, the unpleasant “fishy” smell of discharge from the genital tract - by 41.2 and 5.9%, respectively, discomfort in the genital tract - by 100% in patients of the 1st group with an increase of 62.5% in patients of the 2nd group, the severity of pain during sexual intercourse - by 100% in patients of the 1st group with an increase in the indicator by 40% in patients of the 2nd group, the severity of pathological discharge according to the doctor’s assessment - by 13.0% in patients of the 1st group with no dynamics in patients of the 2nd group (Fig. 7 and 8).
Rice. 7. Dynamics of the level of severity of symptoms of the disease in patients of group 1 before and after treatment.
Rice. 8. Dynamics of the level of severity of symptoms of the disease in patients of group 2 before and after treatment.
When assessing the overall effectiveness of therapy by the patient, the following results were obtained: “marked improvement” was indicated by 29 (96.7%) patients of the 1st group and 20 (66.7%) patients of the 2nd group, “minor improvement” - 1 (3.3%) and 5 (16.7%) patients, respectively, about “condition without changes” - 3 (10.0%) patients of group 2, about “deterioration” - 2 (6.7%) patients 2nd group.
When assessing the overall effectiveness of therapy by a doctor, clinical recovery was registered in 29 (96.7%) patients of group 1 and 20 (66.7%) patients of group 2, significant improvement - in 2 (6.7%) patients 2 group, improvement - in 3 (10%) patients of group 2, condition unchanged - in 1 (3.3%) patient of group 1 and 2 (6.7%) patients of group 2, deterioration — in 3 (10.0%) patients of group 2.
