Clarithromycin in the treatment of urogenital infections

Inflammatory diseases of the urinary tract are among the most frequent causes of treatment of patients to a urologist. In this tract infections in most cases occurs as a mixed pathogenic (gonorrhea, trichomonas, chlamydia, herpes simplex virus) or opportunistic pathogens (ureaplasma, mycoplasma, anaerobes).

The greatest practical interest are intracellular pathogens, such as chlamydia, mycoplasma, ureaplasma. Despite differences in the biological properties of these agents, they all cause similar clinical manifestations of urogenital tract lesions in men (urethritis, uretroprostatitis, epididymitis, although etiological role of these infections in the development of prostatitis is not completely clear, and remains diskutabelnoy (EAU Guidelines on Male Genital Tract Infections, 2007)). For inflammation and chlamydial-mycoplasmal etiology Urea characteristic long latency during chronic, persistent lack of immunity, recurrent nature of the disease, sexual transmission of infection and the difficulty of selection of a rational and effective therapies.

Chlamydia - the smallest gram-negative bacteria with a unique intracellular developmental cycle. They are unable to produce their own energy and live off the energy of the host cell. Are two stages in the life cycle of chlamydia: infectious extracellular form (elementary bodies) and non-infectious intracellular (reticular cells). Elementary (infectious) infects cells mainly of columnar epithelium cells, after which, having passed the stage of metabolically active reticular cells and the stage of intermediate forms, replaced by new elementary bodies, which are released from the cell and infect neighboring. A complete cycle of reproduction of chlamydia - 48-72 hours.

Mycoplasmas belong to the family Mycoplasmataceae. This family is divided into two kinds - the genus Mycoplasma, including about one hundred species (for example, M. hominis, M. genitalium) and the genus Ureplasma, in which there are 3 types (clinical significance U. urealiticum). Manifestation of the pathogenic mycoplasma in the human body due to biological properties: small size, lack cell walls and the similarity of structure of cell membranes with cell membranes of the host organism, resulting in their introduction into the membrane of the cells and makes them more protected from the effects of humoral and cellular immunity factors . These specific features can be explained by the peculiarity of this infection that occurs predominantly latent, asymptomatic.

Urogenital infections are highly contagious. Patients who do not have pronounced symptoms of the disease are particularly at risk of an epidemic of these infections. The incubation period for chlamydia is 2-3 weeks, while mycoplasma from 3 to 5 weeks. Main modes of transmission - sexual, and household contact (rare), vertical.

Along with the acute infection may develop a chronic process. The nature of the disease depends on the human immune system, the massiveness of infection, pathogenicity and virulence of the infectious agent, and many other reasons. Complications of genitourinary disorders mikstinfektsii are expressed immunoregulation associated in particular with the suppression of T-lymphocytes, T-helper cells, decreased levels of interferon status of the patient.

Treatment of urogenital chlamydia - is complex and difficult. Monoinfection is quite rare, it is often compounded by association with other pathogens, sexually transmitted diseases. Intracellular pathogens have a high tropism for epithelial cells in the lesions and persist in specific areas membranoogranichennyh epithelium, which contributes to the experience of the period of drug therapy and may lead to failures in treatment. This makes the application not only etiotropic, but the pathogenetic funds. Inadequate selection of antibiotic and antibiotic irrational regime (dose and duration) may be violating the stages of chlamydia and contribute to their persistence. Thus, antibiotic therapy in patients with urogenital chlamydiosis often does not lead to the elimination of an infectious agent, but only to the clinical symptoms subsided, the translation process in oligosymptomatic symptomatic, subclinical or latent chlamydia. The widespread problem of chlamydial infection and its treatment require a constant search for new drugs and new techniques for their application. It should be noted that the drug is considered effective if its use is achieved eradication of chlamydia is not less than 70% of treated patients.

For the treatment of patients with chronic urogenital chlamydiosis in clinical practice is widely used macrolide antibiotic, showed high efficacy in vitro and in vivo. They are characterized by a small number of side effects and good tolerability. Macrolides have a fairly broad spectrum of activity: Gram-positive bacteria, Gram-negative bacteria, except Enterobacteriaceae, intracellular pathogens and opportunistic pathogens (C. pneumoniae, M. pneumoniae, C. trachomatis, M. hominis, M. genitalium, U. urealiticum etc. .) Macrolide attracts special attention clarithromycin (Klarikar) - semi-synthetic antibiotic acid-fast. It should be emphasized that the pharmacological characteristics of macrolides, including clarithromycin, is their ability to cross cell membranes and accumulate in the cells of the microorganism, including in immunocompetent cells. High clinical efficacy of clarithromycin (Klarikara) are attributed to its anti-inflammatory effect and influence on the functional activity of phagocytes of peripheral blood. It is established that clarithromycin increases the phagocytic activity of neutrophils and macrophages and enhances their migration into the inflammatory focus, where the drug concentration increases in the scores (30-40) times, in addition, it increases the activity of T-killers. In addition, clarithromycin affects the processes of immune response by changing the host's synthesis by monocytes and macrophages critical mediators of the immune response, such as tumor necrosis factor, interleukins, colony-stimulating factor and others, which makes him an antibiotic with immunomodulatory effects on the human body.

Clarithromycin has demonstrated very high activity against S. trachomatis and M. hominis: (MPK50 in vitro 0,007 mg / L and 0.12 mg / L, respectively).

With respect to intracellular pathogens clarithromycin about 8 times more active than erythromycin, which provides a more comfortable double use of the drug in outpatient practice.

преобразуется в печени в активный метаболит √ 14-гидроксикларитромицин, который также обладает антибактериальной активностью. All macrolides ingestion have so-called "effect of the first passage through the liver" to form a pharmacologically inactive metabolites. Clarithromycin is converted in the liver to the active metabolite - 14-gidroksiklaritromitsin, which also has antibacterial activity. In this 14-gidroksiklaritromitsin not inferior (and for a number of pathogens and superior) on the antimicrobial action of the main drug.

Clarithromycin, like other macrolides, has a low degree of ionization and lipid soluble, and therefore is widely distributed in tissues and organs. This antibiotic penetrates well into various cells, microorganism and the maximum concentration of clarithromycin in mononuclear leukocytes and polymorphic serum than in 10-40. Clarithromycin does not create long subingibiruyuschih concentrations, and its absorption is independent of food intake.

Great value and the fact that clarithromycin - this is the only macrolide with high rates of excretion via the kidney (the other macrolides have a pronounced hepatic excretion path). This allows you to receive better clinical efficacy in the treatment of urethritis, prostatitis and other infectious and inflammatory diseases of the urinary system.

The above-described property clarithromycin cause the advisability of appointing the drug for the treatment of patients with inflammatory diseases of the urogenital tract, which are the etiological agents of intracellular pathogens such as Chlamydia, Mycoplasma and Ureaplasma.

In recent years, information was obtained on a high clinical effect of clarithromycin in the treatment of infections, sexually transmitted diseases.

On the combined data from 204 patients with chlamydial urethritis treated with clarithromycin at a daily dose of 200 to 1000 mg for 3-14 days, clinical response was excellent or good in 188, ie, in 92%. In addition, out of 116 patients with urethritis caused by ureaplasma, cure was achieved in 99, ie, 85%. (K. Moricawa, H. Watabe, M. Araake, S. Moricawa).

In another study, a positive result was achieved in 92% of cases of chlamydial urethritis clarithromycin therapy etiology, with almost half of chlamydia was associated with other urogenital infections: Trichomonas, gonococci, mycoplasma (NS Potekaev, N. Potekaev).

Given the positive data from the literature on the effectiveness of clarithromycin in the treatment of urogenital infections were conducted their own study, which allowed to evaluate the effectiveness of this antibiotic in patients with urogenital chlamydial infection.

╩, Pharmacare) в комплексной терапии больных с хламидийным уретритом. Purpose: To evaluate the effectiveness of antibiotic clarithromycin ("Klarikar╩, Pharmacare) in the treatment of patients with chlamydial urethritis.

Materials and Methods: We carried out the etiological diagnosis of infections transmitted predominantly sexually transmitted diseases (STDs) in 95 male patients with chronic urethritis clinic at the age of 18 to 46 years. Indications for examination were complaints of itching, burning and discomfort in the urethra in 14 (14.7%) patients, mucous and pus from the urethra in 13 (13.7%) patients, dysuria (cramps, frequent urination) in 9 (9 5%) patients. 59 (62.1%) patients did not show complaints from the lower urinary tract. The indications for examination in this group of patients were complaints and STI identified in sexual partners. Diagnosis was carried out by the fence material from the urethra, urethral cytologic brush and microscopic examination of smears stained with Romanovsky-Giemsa and direct immunofluorescence reaction (RPIF) for chlamydia, ureaplasma, mycoplasma, trihomanady, gardnerella (╚RecombiSlide╩, NPF "LABdiagnostika"). All patients with chlamydial urethritis etiology in the combined therapy has been appointed as clarithromycin ("Klarikar╩, Pharmacare) in a daily dose of 500 mg for 14 days. Clarithromycin therapy was combined with immunomodulation (tsikloferon, viferon), drugs that improve the microcirculation (trental, chimes), vitamin therapy (aevit, antioxidant complex). The results of therapy and its efficacy assessed after 4 weeks and 2 months after completion of the dynamics of complaints of subjective sensations and the results of control tests.

Results

Diagnosis of STIs identified chlamydial urethritis etiology in 51 (53.7%) patients. In this group, 23 (45.1%) patients diagnosed with chlamydia as monoinfection. In 8 (15.7%) patients with chlamydia were combined with ureaplasmas, 6 (11.8%) with mycoplasmas, 3 patients (5.9%) with T. vaginalis, and 6 (11.8%) with gardnerellezom. 5 patients (9.7%) had mixed infection (chlamydia, mycoplasma, ureaplasma). Clarithromycin was assigned to patients with chlamydial monoinfection (23 patients) as an antimicrobial monotherapy.

In this group of complaints of itching, burning and discomfort in the urethra was presenting 11 (47.8%) patients, mucous or purulent discharge from the urethra - 3 (13.0%) patients, dysuria - 5 (21.7%) patients. 4 (17.4%) patients did not show complaints from the lower urinary tract.

At the completion of therapy, 20 out of 23 patients treated group (87%) reported subjective improvement. Complaints of itching, burning and discomfort in the urethra had disappeared in 8 (72.7%) of 11 patients, dysuria (resident and frequent urination) in all 5 (100%) patients. All patients with mucous or purulent (3 patients), urethral discharge cropped. Among patients who had previously complained of, 3 men (15.8%) noted no subjective improvement. 4 (17.4%) patients in the treatment group had asymptomatic chlamydial urethritis.

In carrying out control tests (RPIF) 4 weeks after completion of therapy chlamydia were diagnosed in 2 (8.7%) patients in a persistent intracellular forms. After 2 months of chlamydia found another 3 patients (13.0%), requiring repeated courses of therapy with a change of antibiotic. Eradication of Chlamydia achieved in 18 (78.3%) patients.

Side effects and allergic reactions while taking clarithromycin ("Klarikar╩, Pharmacare) were observed.

Thus, clarithromycin has proven efficacy against high intracellular pathogens such as chlamydia, mycoplasma, ureaplasma, good tolerability, bioavailability, immunomodulatory effect on macrophage phagocytic-system, with rare side effects that do not require discontinuation of the drug, ease of use.

Conclusions:

Clarithromycin ("Klarikar╩, Pharmacare) is an appropriate antibacterial drug for the treatment of chlamydial urethritis with high efficiency (chlamydia eradication was achieved in 78.3% of patients) and satisfactory tolerability. Receive a daily dose of clarithromycin 500 mg for 14 days, provides a high clinical and microbiological effects.

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