Antibiotic therapy of infections, sexually transmitted infections in pregnant women

The problem of choosing the optimal antimicrobial agent for treating infections, sexually transmitted diseases are discussed in the literature extensively. A pregnant woman needs to pharmacotherapy as much if not more, than nonpregnant women. 60-80% of pregnant women regularly took certain medications (drugs). The factors determining the impact of drugs on the fetus are the chemical properties of the drug, the rate of passage through the placenta, the duration of the maintenance of an effective concentration of the drug, especially the distribution in the tissues of the fetus, placental development stage, the chemical properties (lipophilicity, degree of ionization of the drug, molecular weight, the strength of binding to plasma proteins).

Safety during pregnancy drugs are classified into categories.

∙ A - controlled studies in women showed no risk to the fetus during the first trimester of pregnancy (in the absence of evidence of risk at a later date) and the possibility of harm to the fetus is questionable.

∙ B - animal studies showed no risk to the fetus, but there is no data obtained in controlled studies in pregnant women or animal studies noted adverse effect that was not confirmed in controlled studies in women in the first trimester (when there was no evidence of risk in other trimesters). Category B drugs - is routinely used in pregnancy means (eg, vitamins).

∙ C - in animal studies identified risk to the fetus (teratogenic, or other embriotsidny effect), and controlled studies in women has been conducted, data or laboratory testing on animals are not available. Drugs in this category should be used only when the necessity of its use justifies the potential risk to the fetus.

∙ D-is a proven risk of adverse effects on the fetus, but the possible effect of the drug in pregnant women can take this risk (eg, life-threatening condition). These drugs may be used only when no other safer alternatives.

∙ X - studies on humans or animals have demonstrated adverse effects on the fetus or there is credible evidence of such effects, obtained empirically, and the adverse effects of the drug outweigh the possible benefits. These drugs should not be used in pregnant women.

Modern principles of antibiotic therapy in pregnant women (EA Prokhorovich, 2004) involve consideration of both nonspecific and specific effects on the fetus regardless of whether it is toxic to the mothers.

- общее токсическое действие на плод или возникновение специального повреждающего эффекта (структурного или функционального), тератогенное - аномалия развития (характер порока определяется сроком беременности - началом формирования органа). Specific action is divided into embryotoxic - impact on the zygote and blastocyst (the first 3 weeks), fetotoksicheskoe - general toxic effect on the fetus or the appearance of special damage effects (structural or functional), teratogenic - an anomaly of development (the nature of defect determined by the period of pregnancy - the beginning of the formation of the body) .

Criteria for choosing a BPO (antibiotic) in pregnant women are the efficacy, safety, ease of use (acceptable), economic aspects, preventing breeding and spread of resistant strains.

Efficiency determined by the spectrum of the most probable causative agents of infectious disease, their sensitivity to BPO, data, local resistance agents, the pharmacokinetic characteristics of ABP (penetration into the source of infection, the maintenance and preservation of its concentration sufficient for the eradication of the pathogen). Safety of drugs (drug) is considered the mother's side, and from the fetus.

Safety of drugs from the mother is influenced by renal function, liver allergoanamnezom, chronic diseases, presence of preeclampsia. Safety of drugs from the fetus is determined by a pregnancy, placental permeability, the maturity of enzyme systems of the fetus, renal excretory function in the fetus, the concentration of drug in the amniotic fluid, maternal disease, the presence of preeclampsia.

For example, cephalosporins belong to category B. They pass through the placenta in high concentrations, but negative effects on the fetus have been identified. Aminoglycosides cross the placenta in high concentrations, are in category D, Oto-and nephrotoxicity. Quinolones, fluoroquinolones cross the placenta. Shown to be artrotoksichnost in the experiment. They belong to the category C, and their use in pregnancy is possible only for emergencies.

Glycopeptides also cross the placenta, can cause transient hearing loss in newborns (vancomycin). Vancomycin is prohibited in 1-trimester, category C. Tetracyclines belong to category D, they violate the mineralization of bones and teeth and hepatotoxicity. ABP recommended for use in pregnancy: penicillins, inhibitor-protected penicillins, cephalosporins, macrolides (erythromycin, azithromycin, spiramycin), metronidazole (2 to 3 trimesters), fosfomycin, clindamycin (with caution).

Most often, genital infections, especially in pregnant women, are caused by several pathogenic factors such as viruses, microbes, fungi and protozoa that cause similar to the clinical course, but different in the pathogenesis of the disease and treatments. Despite the significant progress made in diagnosis, therapy and prevention of these infections, their frequency does not have a distinct downward trend.

Since the results of studies conducted in the Scientific Center for Obstetrics, Gynecology and Perinatology, a combination of Chlamydia with gonococcus observed in 33.7% of patients with ureamikoplazmozom - in 19.1%, with gardnerellas - at 9.9%. Simultaneously, three different infections diagnosed in 10.6% of patients, 4-5 infections - at 5.6%. The most commonly diagnosed infections include urinary tract Chlamydia. Similar results were obtained by Belarusian obstetricians with an indication of the low incidence of bacterial eradication in the case of erythromycin as a means of antimicrobial therapy (S. Mikhalevich, 2006): "Treatment of infection with erythromycin ureamikoplazmennoy not yield the desired results: the elimination of M. hominis in the appointment of erythromycin does not occur in 62.5% of cases, and U. urealyticum in 70% of cases. "

According to the Centers for Disease Control, USA (US Centers for Disease Control and Prevention, CDC), the prevalence of chlamydial infection in pregnant women ranges from 2 to 24%. In 25-50% of infants born to infected women, chlamydial infection develops the eye, at 10-20% - Chlamydia pneumonia (J. Schachter, 1995). The risk of transmission to the newborn is about 70%. The need for treatment of urogenital Chlamydia trachomatis in pregnancy, if for different reasons could not be conducted prior to pregnancy, there is no doubt among experts.

According to the Russian government in 2006 for chlamydial infection in pregnant women are the drugs of choice:

∙ Azithromycin - 1.0 g once;
∙ Erythromycin - 500 mg 4 times daily for 7 days;
∙ Amoxicillin - 500 mg 3 times a day, 7 days.

In the European leadership of the main drugs appear:
∙ Erythromycin base 500 mg orally four times a day - 7 days;
∙ Amoxicillin 500 mg orally 3 times a day - 7 days;
∙ dzhozamitsin 750 mg orally 2 times a day - 7 -14 days.

Alternatives are the following schemes:
∙ Erythromycin base 250 mg orally 4 times a day - 14 days;
∙ erythromycin ethyl succinate 800 mg orally 4 times a day - 7 days, or 400 mg - 14 days;
∙ azithromycin 1.0 g once inside.

The new version of the Manual of SDS 2006. recommends a single dose of azithromycin as a primary treatment regimen of chlamydial infection in pregnant women. Erythromycin was first translated into the category of alternative medicines.

Why does azithromycin took the first place in the treatment of chlamydial infection in pregnant women? The emergence of azithromycin as a basic treatment for sexually transmitted infections in pregnant women suggests that to date has collected enough information on the impact of azithromycin, as in the planned research, and as a result of accidental use in pregnant. Reliable data on adverse effects on the fetus has not yet received azithromycin. Azithromycin is a semisynthetic macrolide only one belonging to category B.

According to V. Simunic and colleagues, the efficacy of 1 g of azithromycin in the treatment of chlamydial infection in pregnant women was 92.1%, a seven-day course of erythromycin - 87.5%. At the same compliance and tolerability of treatment with azithromycin were much better, and pregnancy outcomes in the groups did not differ significantly.

In a study of CD Adair et al., (1998) was shown comparable therapeutic effect of azithromycin and erythromycin - 88.1 and 93.0%. Tolerability of treatment with azithromycin was much higher than with erythromycin (58.1% in patients treated with erythromycin, developed side effects and 18.6% had to discontinue treatment). Studies also indicate that the microbiological cure during pregnancy does not guarantee against future disease or postpartum neonatal manifestations of chlamydial infection in women.

Thus, azithromycin, in recent years has taken a leading position as an antibacterial agent in the treatment of sexually transmitted infections in pregnant women. This is due to many of the features of this antibiotic, such as the optimal range of the basic agents of sexually transmitted infections in pregnant women (chlamydia, ureaplasma, mycoplasma), long half-life, high absorption and stability in acidic medium, the ability to be transported by leukocytes to the site of inflammation, high and prolonged concentration in the tissues, the possibility of penetration into the cell, well-tolerated. But the main drug for treating urogenital chlamydial infections in pregnant women azithromycin was primarily due to their low toxicity and safety to the fetus ..

An important feature of the pharmacokinetic of azithromycin is the creation of high and stable concentrations in the tissues and media of the reproductive organs, and this can be achieved even with single dose. So, 24 hours after a single oral dose of 1 g of the drug levels in prostate tissue was 94 mg / l after 48 hours - 54 mg / l and even after 3 weeks, it remains above the MIC for C.trachomatis - one of the most common pathogens of prostatitis. High concentrations of azithromycin exceeding the MIC for N.gonorrhoeae, C.trachomatis and U.urealyticum, are also in the juice of the prostate and semen. Concentrations of azithromycin in cervical mucus on the first day after administration of 1 g single dose of 9.5 times over 7 days - 5.5 times higher than concentrations in serum. Noted the accumulation of antibiotics and other pelvic organs in women (Strachunsky LS, 2002). When applied in pregnant women in a dose of 500 mg of azithromycin concentrations in serum of umbilical cord blood and amniotic fluid close to those in maternal serum (0.028 mg / ml).

The highest concentration observed in the placenta (2 mg / kg). In the tissues of azithromycin is localized mainly intracellularly, accumulating in large quantities particularly in the lysosomes of alveolar macrophages, neutrophils, monocytes and fibroblasts, the latter represent the most extensive and stable depot of the drug. According to the degree of accumulation of azithromycin in these cells has advantages over other macrolides. Due to the accumulation in phagocytes, azithromycin can actively capture from the blood, interstitial fluid and fibroblasts, the drug selectively distributed in the pockets of infectious inflammation.

On the basis of GKVD in the period from 2004 to 2007. STIs were treated 41 pregnant women. Microbiological diagnosis of mycoplasma ureaplasmosis and determined on the basis of quantitative culture for U. urealiticym, M. hominis; diagnosis of chlamydia - by IFA or PCR, in difficult diagnostic cases used ELISA Ig M, A, G Chlamydia trachomatis. Monoinfection was detected in 15 (37%) patients: in 5 (12%), ureaplasma, 3 patients (7%), mycoplasma, chlamydia - 7 (17%).

Mixed infections were detected in 26 (63%) patients: 12 (29%), chlamydia, and ureaplasma, 6 (15%), chlamydia and mycoplasma, 5 (12%), ureaplasma and mycoplasma, 3 (7%), ureaplasma, mycoplasma, chlamydia . In 24 (59%) patients with bacterial infection combined with symptomatic urogenital candidiasis. Given the available data from the literature and the experience of azithromycin in the Republic of Belarus in pregnant women, patients were assigned to "Azikar" (Farmakar) at a daily dose of 500 mg of 7 days. Treatment was well tolerated by all patients. Adverse events during therapy were observed. Microbiological cure was achieved in 37 (90.2%) patients: in monoinfection in 14 (93.3%) women - 4 (80%) patients ureaplazmozom, 3 (100%) - mycoplasmosis, 7 (100%) - chlamydia. The positive effect of therapy in the mixed infection was observed in 23 (88.5%) patients: in 11 (91.7%) when combined chlamydia and ureaplasma, 6 (100%) - chlamydia and mycoplasma, 4 (80%) - ureaplasma and mycoplasma, in 2 (66.7%) - ureaplasma, mycoplasma, chlamydia. Mikrobiologichskaya cure was not achieved in the case of a patient with monoinfection ureaplazmozom and in 3 cases, mixed infection.

Lack of effect in relation to cases arising from infection by U. urealiticym, due to the presence of strains resistant to azithromycin and the lowest activity of azithromycin against pathogens ureaplasmosis. In these cases, the drug of choice may be clarithromycin ("Klarikar").

The data presented indicate a high efficacy of STIs in pregnant women drug "Azikar" (azithromycin Farmakar). No side effects and tolerability of drug confirm the available literature data on the high komplaentnosti in therapy is not only pregnant, but pregnant women.

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