THE CHOICE OF ANTIMICROBIAL THERAPY AMONG PHYSICIANS IN THE TREATMENT OF GESTATIONAL PYELONEPHRITIS

1) FGBU Scientific Center for Obstetrics, Gynecology and Perinatology. Academician VI Kulakov Russian Ministry of Health, 4, Oparin street, Moscow, Russian Federation, 117997, e-mail: chuhareva@mail.ru 2) NRU BSU, dep. pharmacology; Multidisciplinary clinic "Harmony Health" – the center of the safe pharmacotherapy pregnant and nursing; Belgorod, 85 Pobedy St., Belgorod, 308015, Russian Federation, e-mail: bontsevich@bsu.edu.ru 3) NRU BSU, dep. pharmacology, Belgorod, 85 Pobedy St., Belgorod, 308015, Russian Federation, e-mail: 572804@bsu.edu.ru 4) NRU BSU, Belgorod, 85 Pobedy St., Belgorod, 308015, Russian Federation, e-mail: 562158@bsu.edu.ru


Introduction:
Gestational pyelonephritisan inflammatory process that occurs in the interstitial kidney tissue and renal pelvis system, which can occur during pregnancy, childbirth or the postpartum period.The prevalence of the disease is sufficiently largenoted that during gestation they suffer from 1 to 10% of women [1,2].Acute pyelonephritis is the most common inflammatory process (10-12%) [3,4,5] occurring in the kidney during pregnancy.
It is believed that a woman's body becomes more susceptible to the disease during pregnancy for many reasonsa violation of passage of urine by the ureters iz-za hormonal changes (relaxation of smooth muscles of the ureter, renal pelvis expansion of the system under the influence of progesterone, the occurrence of vesicoureteral reflux) , compression of the ureter enlarged uterus (particularly common in nulliparous due to the elasticity of muscles anterior abdominal wall) [6], the strong growth of pathogenic microflora under the influence of estrogens [2,4,7].Under the influence of these causes may occur stagnation of urine with infection and the development of gestational pyelonephritis.
Gestational pyelonephritis and worsens the prognosis of pregnancy and can cause premature delivery, hypertensive disorders, pre-eclampsia and Timely detection and appropriate treatment initiated pyelonephritis can significantly improve the quality of life of the pregnant, prevent most complications both during pregnancy and in the postpartum period.
According to clinical guidelines, the main treatment of pyelonephritis in pregnant women is antibiotic therapy, which would meet the basic requirements of safety and efficiency for both the mother and the fetus [9,10].Due to the large number of complications and the risk of pyelonephritis treatment should begin immediately after diagnosis, without waiting for the results of urine culture, that is, conduct empirical antibacterial drugs treatment of a wide spectrum of action, based on the most common causative agents of the disease [6,8].
According to the Federal Clinical guidelines in 2014 the drugs of choice in the treatment of pyelonephritis in pregnant women are cephalosporins III generationceftibuten, cefixime, cefotaxime, ceftriaxone, which have a broad spectrum of antibacterial activity and can be used at any stage of pregnancy.According to the USA classification of drugs FDA (Food and Drug Administration -FDA) cephalosporins are classified in safety of use during pregnancy [11,12].In addition to the cephalosporins, as a rational pharmacotherapy is possible to use the drug group monobactamsaztreonam (Category B classification FDA) [8].
With the ineffectiveness of these drugs, chronic and long-term course of the disease, in pregnant women for indications of alternative treatment may be applied -gentamicin + ampicillin (appointed after the II trimester) [9], category C by the FDA, [8,13].If you have restrictions on the use of aminoglycosides can be assigned to the group preparations of carbapenems, including meropenem, ertapenem, imipenem / cilastatin (Category B classification FDA) [9].Also as can be seen altarnativnoy therapy drugs penicillins in combination with β-lactamase inhibitorspiperacillin / tazobactam, ticarcillin / clavulanate (B according to FDA) [9] and generation cephalosporin IVcefepime.
The most prominent common and useful drug for gestational pyelonephritisamoxicillin / clavulanate, currently can not be recommended as empirical therapy, because of the large kolichesvo isolated strains of E. coli, resistant to the drug (up 43.0%) [3].Amoxicillin / clavulanic acid, as well as cephalosporin II generation (cefuroxime) appointed in pregnant women only after the culture results of urine on chuvsvitelnost to antibiotics.
In view of the prevalence and social significance of the disease, a large number of complications, the empirical selection of antibacterial therapy at the beginning of treatment due to the timing of gestation and the severity of the patient's condition [18], it is expedient to hold a pharmacoepidemiological study in order to identify the preferences of physicians in the selection of Antimicrobial Chemotherapy (ACT) pyelonephritis pregnant .

Objective:
To analyze the choice of Belgorod region ACT doctors in the treatment of pyelonephritis in pregnancy.Compare the data with the results obtained as a result of the survey, which was conducted from February to April 2015, four federal districts of the Russian Federationthe Central, Volga, Urals and Far East.
Materials and Methods: In this study based on the method of anonymous questionnaire in the framework of the second stage of the All-Russian pharmacoepidemiological study, "Epidemiology of the use of drugs in pregnant women", which was conducted from February to April 2015.All-Russian Pharmacoepidemiological 1066 questionnaires were analyzed in the study, of which 734 obstetricians and gynecologists, and 332 physician [19].
Information obtained from the survey were entered and processed using MicrosoftExel program.
Amoxicillin / clavulanate (without preliminary urine culture sensitivity to the drug) 50.0% of physicians chose the Belgorod region (57.1% of obstetricians and gynecologists and 17.7% of physicians, p = 0,003) and 49.1% of the doctors at the All-Russia study (p = 0,861).
A large number of responses were given ineffective as a therapy of pyelonephritis is not protected against beta-lactamase penicillins -CP doctors pointed them in 55.3% of the questionnaires (51.9% and 70.6% of obstetricians Physicians, p = 0,161), the All-Russian doctors in the study 32.9% of the questionnaires (p <0,0001).Cefazolin (cephalosporin II generation) 27.7% of physicians chose the Belgorod region (32.5% of obstetriciangynecologist and 5.9% of the therapist, p = 0.02) and 15.6% of physicians All-Russia study, p = 0.002.
Macrolides having low activity against gramnegative microflora was given to 31.9% of the responses in the BR (37.7% of obstetricians and gynecologists and internists 5.9%, p = 0.01) and 18.4% of responses at All-Russia study, p = 0.0015.
Fosfomycin, a drug that is used only for the treatment of cystitis and bacteriuria, indicated in their questionnaires, 30.9% of physicians BR (32.5% and 23.5% of obstetricians Physicians, p = 0.470) and 19.6% of doctors of All-Russian Research, p = 0.009.
Absolutely contraindicated in the treatment of gestational pyelonephritis fluoroquinolones are listed in the individual questionnaires BR physicians (2.1%) and the All-Russia survey (2.2%).
Send their patients for treatment to another specialist doctors decide 26.6% BR (28.7% of obstetricians and gynecologists and 17.6% of physicians, p = 0.356) and 32.3% of All-Russian research physicians (p = 0.257).Compare tactics ACT doctors BR and All-Russia study are shown in Table 1 and Figure 1.

Conclusion:
According to the data of the survey, about half of the doctors of the Belgorod region and the All-Russian Research prescribe rational pharmacotherapy in the treatment of gestational pyelonephritis (in particular, Cephalosporin III generation), p = 0.054.
From about the same, but without specifying what perparaty data can be allocated only after urine culture sensitivity operedeleniya rate doctors opt to amoxicillin / clavulanate (p = 0.861) and cephalosporin II generation (p = 0.523).
Regardless of the national recommendations, the canons of rational antibiotic therapy, doctors BR and All-Russian Research continue to prescribe their patients previously ineffective drugs in the treatment of pyelonephritismacrolides (p = 0.0015) and fosfomycin (p = 0.009).
Reserve antimicrobialsamnoglikozidy, vancomycin, meropenemchose only doctors All-Russian Research; cephalosporin IV generation was given roughly equal number of votes (p = 0.702), however, none of the doctors did not indicate that they prescribe them for health reasons, in the case where the appointment of benefit to the mother outweighs the potential risk for the development of the fetus.
insufficiency, hypoxia and infection of the fetus in utero, and even abortion [2].

Figure 1 .
Figure 1.The purpose frequency pyelonefrite drugs in pregnant women among obstetrician-gynecologists and internists Belgorod region of the Russian Federation