National Medical University named after O.O. Bohomolets, Kyiv
State Institution “Institute of Urology of National Academy of Sciences of Ukraine”, Kyiv

Summary. The article presents the results of research of clinical and microbiological efficacy of Grandazol in the comprehensive treatment for inflammatory disorders of male genital organs of trichomonal bacterial origin.
Key words: inflammatory disorders of male genital organs, urogenital trichomoniasis, sexually transmitted infections, Grandazol.

Inflammatory infections in the urology and issues of their treatment and prevention represent one of the most pressing problems of the contemporary medicine. This is due to their prevalence, frequent recurring, social-economic and reproductive significance as well as to the progressing growth of microorganisms’ resistance to antibiotics [1].

Despite significant achievements in the research of origin and pathogenesis in introduction of new methods of diagnostics and treatment, inflammatory disorders of male genital organs (IDMGO) are high on the list among urologic diseases.

Every year an increasing spread of IDMGO is observed, therefore treatment of this pathology becomes currently particularly critical [2].

The etiological factor of IDMGO is both nonspecific microflora and pathogens of sexually transmitted infections (STI).

As of today, the STI reached epidemic proportions in Ukraine. This is determined by a whole number of factors: low level of the population’s sexual culture; a broad liberalization of sexual relationships; early sexual debut and lack of awareness about means of contraception; low level of financial security; insufficient and imbalanced nutrition; environmentally unfavorable conditions; hereditary and iatrogenic disorders of local and systemic immunity; active migration processes; decreasing quality and
efficiency of preventive and clinical work of medical institutions due to inadequate funding; complexity of diagnostics; change in microflora spectrum and increasing amount of strains of microorganisms that have preserved their pathogenic properties after inferior and inadequate treatment; asymptomatic or pauci-symptomatic course of this disease; lack of immunity after recovery [3, 8, 16, 17].

Urogenital trichomoniasis (UT) is a widespread STI the pathogen of which is Trichomonas vaginalis – a protozoan single-celled microorganism adapted in the course of evolution to parasitization in organs of human genitourinary system [20]. Trichomoniasis is a widespread disease and ranks first among sexually transmitted diseases [4]. The world database receives reports on 170 – 200 millions of trichomoniasis cases annually [5–8]. The infection frequency in the developed countries amounts to 2-10%, and in developing countries – 15-40%. Among patients with a mixed urogenital infection, carriers
of trichomonas amount to 40-50%, at that the disease is in 50% of cases asymptomatic. It should be taken into account that carriage of trichomonas leads to an epidemiological dissemination of pathogens among sexual partners [3, 9, 10].

In Ukraine, the official UT incidence rate is 1,263.7 cases for 100,000 of population, however, the real indicator is 5 times higher and amounts to some 6% of the whole population or 12% of sexually active population of reproductive age [11].

Trichomonal infection is the cause of emergence of IDMGO in 23-40% of patients and, respectively, being a widespread disease, it impacts the population’s reproductive function and the demographic situation [12, 18]. One characteristic feature of Trichomonas vaginalis is their exceptional capacity for the association with other STI pathogens, therefore UT often develops along with a concurrent infection (together with chlamydial, ureaplasma, mycoplasmal infections and gonorrhea), which makes its treatment more difficult and contributes to emergence of complications. Trichomonas often serve as
reservoirs, whilst preserving these pathogens in unchanged state (endocytobiosis), and some of them even actively replicate inside of Trichomonas vaginalis [13-15].

Trichomonas vaginalis affects urinary tract, seminal vesicles, prostate gland. UT entails the following complications in men: balanitis, balanoposthitis, urethritis, paraurethritis, cowperitis, epididymitis, prostatitis, vesiculitis, cyctitis [19].

The complexity of clinical laboratory diagnostics of a bacterial infection lies in the availability of simultaneously 2-3 and more various pathogens. Certain difficulty in identification of the disease in men is related to peculiarities in the genital system’s constitution. In case of a trichomonal lesion of the prostatic urethra part and prostate at the expense of a barrier function of the membranous sphincter, it is not always possible to reveal a pathogen in excretes [24].

As to the morphology of trichomonas, the number of their atypical forms has increased. These forms possess low mobility and have an ameboid or spherical shape, which complicates a bacterioscopical diagnosis. Frequent absence of pathognomic clinical implications of urogenital trichomoniasis, its course with minimal clinical implications make laboratory methods a basis for diagnosis of the disease. Judgments of many kinds with respect to diagnosis methods can be found in literature, which to a certain degree misleads practicing physicians. The selection of research methods when identifying sexually transmitted infections depends on many factors: anamnestic data, examination results, preliminary research (direct smear), list of laboratory tests conducted in a clinic, their cost, the patient’s wherewithal. Thus, the selection of methods and examination algorithm should not only correspond to the regulatory environment (protocols, standards) but also be individual for each patient. Preparation of a patient and material sampling technique certainly have an effect on the quality of the diagnosis process.

In order to receive more reliable data, the following rules must be adhered to:
– a negative result of any examination does not exclude the presence of trichomonas;
– examination of material obtained should be carried out by all accessible methods simultaneously;
– it is necessary to use for the assessment not only urethral discharge and prostatic secretion, but also uropsammus of freshly voided urine, secretion of bulbourethral glands, sperm [18, 21].

The complexity of IDMGO treatment is due to the high virulence and resistance of pathogens to antibacterial drugs applied in urological practice, with persistent course of a disease and weakening of body defenses.

When determining a background therapy for treatment of STI, account should be taken of the WHO recommendations as to the criteria for antibacterial drug selection. The requirements envisage:
– high efficacy;
– low toxicity and good tolerability;
– slow development of the pathogen’s resistance to applied medicinal products;
– opportunity to reduce administration frequency;
– opportunity to take drugs orally.

The quality of an efficient and timely therapy against trichomoniasis contributes greatly to the disease’s expansion, course and prognosis. The treatment success depends on a right individual selection of the medicinal product, its pharmacokinetics and pharmacodynamics. The therapy’s inefficiency is often linked to the noncompliance with the recommended treatment regimen or re-infection.

During a combination treatment of IDMGO, it is advisable to use antibacterial drugs with a broad spectrum of action. With reference to the wide spectrum of possible pathogens the structure of which includes, as a rule, anaerobic microbes, the tendency of Trichomonas vaginalis to endocytobiosis, the treatment regimens with inclusion of antibiotics and imidazoles are the most rational and practiceproven, in particular, during the acute and subacute periods of disease. Two, or sometimes more individual medications are included into these regimens. The combined antibacterial medications that became available in recent years, allow conducting treatment with a single medicinal product, thus enhancing patient compliance, considerably increasing the treatment efficacy and reducing the drug load on the organism [13].

These properties are displayed by the combined antibacterial medication Grandazol which contains active substances levofloxacin (2.5 mg/ml) + ornidazole (5 mg/ml). The medication is available in 100 ml vials (250 mg levofloxacin + 500 mg ornidazole) and 200 ml (500 mg levofloxacin + 1,000 mg ornidazole); in tablets (250 mg levofloxacin + 500 mg ornidazole).

The availability of various drug forms of Grandazol enables the use in the acute period of infusion (intravenous) administration route, ensuring 100% bioavailability and high concentration of the active ingredient in blood plasma within shortest time, with subsequent transfer of the patient to oral administration without dose adjustment [27].

Levofloxacin is an antibiotic that belongs to the group of fluoroquinolones. The fluoroquinolones are fundamentally different from other antimicrobial drugs by their mode of action. Their bactericidal effect is attributable to inhibition of two vitally important ferments of a microbial cell – DNA-gyrase and topoisomerase IV which results in a disturbance of synthesis of a bacterial DNA. Levofloxacin is active in respect of gram-positive and gram-negative pathogens including strains resistant to penicillins, cephalosporins and aminoglycosides. The advantages of levofloxacin: administration once a day; favourable pharmacokinetics; high level of penetration of prostate tissues; good bioavailability; similar pharmacokinetic parameters at oral and parenteral administration; high activity in respect of STI pathogens (Mycoplasma hominis, Ureaplasma urealyticum, Chlamydia trachomatis, Neisseria gonorrhoeae) [25, 26].

Ornidazole is a synthetic drug of nitroimidazole group with antibacterial (anti-anaerobic) and antiprotozoal action. Its antitrichomonal activity is due to the presence of a nitro group in the molecule. The nitro radical is able to break down DNA strings of a trichomonal cell. The effect emerges quickly. Cell division and cell mobility are terminated within 1 hour, and the cell itself dies within 8 hours [22].

The spectrum of action of Grandazol corresponds to its components – ornidazole and levofloxacin:
Staphylococcus spp., Streptococcus spp., Enterococcus spp., Enterobacter spp., H.influenzae, Legionella spp., Е.coli, Klebsiella spp., Salmonella spp., Proteus spp., Shigella spp., N.gonorrhoeae, Chlamydia trachomatis, Mycoplasma hominis, Ureaplasmaurealyticum, Bacteroides fragilis, Clostridium spp., Peptostreptococcus spp., Peptococcus spp., Gardnerella vaginalis, and also Trichomonas vaginalis etc.

Objective of paper: to study efficacy, safety and tolerability of Grandazol (manufactured by Yuria- Pharm) as well as its impact on the clinical course and laboratory indicators when treating IDMGO of trichomonal and bacterial origin.