В обзоре представлены современные литературные данные по эпидемиологии, этиологии, патогенезу, диагностике и лечению воспалительных заболеваний органов малого таза (ВЗОМТ). Медико-социальные последствия ВЗОМТ, связанные с негативным влиянием на женское репродуктивное здоровье, подчеркивают необходимость своевременного проведения антибактериальной терапии, направленной на эрадикацию всех потенциальных этиотропных агентов из воспалительного очага. В статье проведен сравнительный анализ преимуществ и некоторых ограничений стандартных лечебных стратегий, разработанных для применения в ситуациях с ВЗОМТ на территориях Российской Федерации, США и Европы. С учетом повсеместного распространения антибиотикорезистентности к фторхинолонам, недостаточной чувствительности к антибиотикам 1-й линии (доксициклин) у отдельных возбудителей (в частности, Mycoplasma genitalium) в схему лечения ВЗОМТ наряду с цефалоспоринами II–III поколения, метронидазолом целесообразно рекомендовать включение азитромицина в качестве антибактериального препарата 1-го выбора. Ключевые слова: воспалительные заболевания органов малого таза, Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, микроорганизмы, ассоциированные с бактериальным вагинозом , антибиотикотерапия, азитромицин.
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This review presents the current published data on the epidemiology, etiology, pathogenesis, diagnosis and treatment of pelvic inflammatory disease (PID). Medical and social consequences of PID associated with the negative impact on women's reproductive health, emphasize the need for early antimicrobial therapy aimed at eradication of all potential etiotropic agents of the inflammatory focus. In the article the comparative analysis of the advantages and some limitations of conventional therapeutic strategies designed for use in situations with PID on Russian territory, the United States and Europe. Given the ubiquity of fluoroquinolone antibiotic resistance, insufficient sensitivity to first-line antibiotics (doxycycline) in the individual agents (in particular, Mycoplasma genitalium) treating PID in the circuit along with II–III generation cephalosporin, metronidazole, and it is desirable to recommend inclusion of azithromycin as an antibacterial drug first selection. Key words: pelvic inflammatory disease, Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, bacterial vaginosis associated microorganisms, antibiotic, azithromycin.
1. Wiesenfeld HC, Sweet RL, Ness RB et al. Comparison of acute and subclinical pelvic inflammatory disease. Sex Transm Dis 2005; 32: 400–5.
2. Bevan CD, Ridgway GL, Rothermel CD. Efficacy and safety of azithromycin as monotherapy or combined with metronidazole compared with two standard multidrug regimens for the treatment of acute pelvic inflammatory disease. J Int Med Res 2003; 31: 45–54.
3. Общая заболеваемость взрослого населения России в 2014 году ФГБУ «Центральный научно-исследовательский институт организации и информатизации здравоохранения» Министерства здравоохранения Российской Федерации. URL: http://www.mednet.ru/index.php?option=com_user&view=login&return=aHR0cDovL3d3dy5tZWR... / Obshchaia zabolevaemost' vzroslogo naseleniia Rossii v 2014 godu. FGBU «Tsentral'nyi nauchno-issledovatel'skii institut organizatsii i informatizatsii zdravookhraneniia» Ministerstva zdravookhraneniia Rossiiskoi Federatsii. URL: http://www.mednet.ru/index.php?option=com_user&view=login&return=aHR0cDovL3d3dy5tZWR... [in Russian]
4. Практическое руководство по антиинфекционной химиотерапии. 2-е изд. Под ред. Л.С.Страчунского, Ю.Б.Белоусова, С.Н.Козлова. Смоленск: МАКМАХ, 2007. / Prakticheskoe rukovodstvo po antiinfektsionnoi khimioterapii. 2-e izd. Pod red. L.S.Strachunskogo, Iu.B.Belousova, S.N.Kozlova. Smolensk: MAKMAKh, 2007. [in Russian]
5. Sweet RL Treatment of acute pelvic inflammatory disease. Infect Dis Obstet Gynecol. 2011; 561909.
6. Haggerty CL, Schulz R, Ness RB. Lower quality of life among women with chronic pelvic pain after pelvic inflammatory disease. Obstet Gynecol 2003; 102 (5): 934–9.
7. Burnett AM, Anderson CP, Zwank MD. Laboratory-confirmed gonorrhea and/or chlamydia rates in clinically diagnosed pelvic inflammatory disease and cervicitis. Am J Emerg Med 2012; 30: 1114–7.
8. Ness RB, Kip KE, Hillier SL et al. A cluster analysis of bacterial vaginosis-associated microflora and pelvic inflammatory disease. Am J Epidemiol 2005; 162: 585–90.
9. Brunham RC, Gottlieb SL, Paavonen J. Pelvic inflammatory disease. N Engl J Med 2015; 372: 2039–48.
10. Oakeshott P, Aghaizu A, Hay P et al. Is Mycoplasma genitalium in women the "New Chlamydia?" A community-based prospective cohort study. Clin Infect Dis 2010; 51: 1160–6.
11. Ross J, Judlin P, Jensen J. International Union against sexually transmitted infections. 2012 European guideline for the management of pelvic inflammatory disease. Int J STD AIDS 2014; 25 (1): 1–7.
12. Гинекология: национальное руководство. Под ред. В.И.Кулакова, И.Б.Манухина, Г.М.Савельевой. М.: ГЭОТАР-Медиа, 2011. / Ginekologiia: natsional'noe rukovodstvo. Pod red. V.I.Kulakova, I.B.Manukhina, G.M.Savel'evoi. M.: GEOTAR-Media, 2011. [in Russian]
13. CDC. Sexually Transmitted Disease Treatment Guidelines.Pelvic Inflammatory Disease. MMWR. 2015.
14. Wiesenfeld HC, Hillier SL, Meyn LA et al. Subclinical pelvic inflammatory disease and infertility. Obstet Gynecol 2012; 120: 37–43.
15. Tepper NK, Steenland MW, Gaffield ME et al. Retention of intrauterine devices in women who acquire pelvic inflammatory disease: a systematic review. Contraception 2013; 87: 655–60.
16. Hillis SD, Joesoef R, Marchbanks PA et al. Delayed care of pelvic inflammatory disease as a risk factor for impaired fertility. Am J Obstet Gynecol 1993; 168 (5): 1503–9.
17. Clinical Effectiveness Group. UK national guideline for the management of pelvic inflammatory disease 2011. London (UK): British Association for Sexual Health and HIV, 2011.
18. Hillier SL, Kiviat NB, Hawes SE et al. Role of bacterial vaginosis-associated microorganisms in endometritis. Am J Obstet Gynecol 1996; 175 (2): 435–41.
19. Серов В.Н., Ильенко Л.Н. Биологические эффекты эндотоксина и клинико-патогенетические реакции при воспалительных заболеваниях половых органов у женщин. Акушерство и гинекология. 1997; 3: 11–3. / Serov V.N., Il'enko L.N. Biologicheskie effekty endotoksina i kliniko-patogeneticheskie reaktsii pri vospalitel'nykh zabolevaniiakh polovykh organov u zhenshchin. Akusherstvo i ginekologiia. 1997; 3: 11–3. [in Russian]
20. Eschenbach DA. Acute pelvic inflammatory disease: etiology, risk factors and pathogenesis. Clin Obstet Gynecol 1976; 19: 147.
21. Bjartling C, Osser S, Persson K. Mycoplasma genitalium in cervicitis and pelvic inflammatory disease among women at a gynecologic outpatient service. Am J Obstet Gynecol 2012; 206 (6): 476.e1-476.e8.
22. Bjornelius E, Anagrius C, Bojs G et al. Antibiotic treatment of symptomatic Mycoplasma genitalium infection in Scandinavia: a controlled clinical trial. Sex Transm Infect 2008; 84 (1): 72–6.
23. Jernberg E, Moghaddam A, Moi H. Azithromycin and moxifloxacin for microbiological cure of Mycoplasma genitalium infection: an open study. Int J STD and AIDS. 2008; 19 (10): 676–9.
24. Workowski KA, Berman SM, Douglas JM, Jr. Emerging antimicrobial resistance in Neisseria gonorrhoeae: urgent need to strengthen prevention strategies. Ann Intern Med 2008; 148: 606–13.
25. Bradshaw CS, Chen MY, Fairley CK. Persistence of Mycoplasma genitalium following azithromycin therapy. PLoS ONE 2008; 3 (11): Article ID e3618.
26. Бондаренко К.Р., Бондаренко В.М. Бактериальные липополисахариды в патогенезе гинекологических заболеваний и акушерских осложнений. Журн. микробиологии, эпидемиологии и иммунобиологии. 2014; 4: 80–6. / Bondarenko K.R., Bondarenko V.M. Bakterial'nye lipopolisakharidy v patogeneze ginekologicheskikh zabolevanii i akusherskikh oslozhnenii. Zhurn. mikrobiologii, epidemiologii i immunobiologii. 2014; 4: 80–6. [in Russian]
27. Доброхотова Ю.Э., Дубнер Н.Ю. Моксифлоксацин в лечении воспалительных заболеваний органов малого таза. Фарматека. 2005; 2: 68. / Dobrokhotova Iu.E., Dubner N.Iu. Moksifloksatsin v lechenii vospalitel'nykh zabolevanii organov malogo taza. Farmateka. 2005; 2: 68. [in Russian]
28. Lanjouw E, Ouburg S, de Vries HJ et al. 2015 European guideline on the management of Chlamydia trachomatis infections. Int J STD AIDS 2016; 27 (5): 333–48.
29. Kintner J, Lajoie D, Hall J et al. Commonly prescribed β-lactam antibiotics induce C. trachomatis persistence/stress in culture at physiologically relevant concentrations. Front Cell Infect Microbiol 2014; 4: 44.
30. Мартинович А.А., Эйдельштейн М.В., Цюман Ю.П., Козлов Р.С. Азитромицин: сравнение качества инъекционных лекарственных форм оригинального препарата и его воспроизведенных препаратов. Клин. микробиология и антимикробная химиотерапия. 2011; 14 (4): 252–8. / Martinovich A.A., Eidel'shtein M.V., Tsiuman Iu.P., Kozlov R.S. Azitromitsin: sravnenie kachestva in"ektsionnykh lekarstvennykh form original'nogo preparata i ego vosproizvedennykh preparatov. Klin. mikrobiologiia i antimikrobnaia khimioterapiia. 2011; 14 (4): 252–8. [in Russian]
31. Parnham MJ, Erakovic Haber V, Giamarellos-Bourboulis EJ et al. Azithromycin: mechanisms of action and their relevance for clinical applications. Pharmacol Ther 2014; 143 (2): 225–45.
32. Козлов Р.С., Дехнич А.В. Справочник по антимикробной терапии. Смоленск: МАКМАХ, 2013. / Kozlov R.S., Dekhnich A.V. Spravochnik po antimikrobnoi terapii. Smolensk: MAKMAKh, 2013. [in Russian]
33. Клинические рекомендации. Акушерство и гинекология. 4-е изд. Под. ред. В.Н.Серова, Г.Т.Сухих. М.: ГЭОТАР-Медиа, 2014. / Klinicheskie rekomendatsii. Akusherstvo i ginekologiia. 4-e izd. Pod. red. V.N.Serova, G.T.Sukhikh. M.: GEOTAR-Media, 2014. [in Russian]
34. Приказ Министерства здравоохранения Российской Федерации от 24.12.2012 №1502н «Об утверждении стандарта первичной медико-санитарной помощи при воспалительных заболеваниях половых органов». / Prikaz Ministerstva zdravookhraneniia Rossiiskoi Federatsii ot 24.12.2012 №1502n «Ob utverzhdenii standarta pervichnoi mediko-sanitarnoi pomoshchi pri vospalitel'nykh zabolevaniiakh polovykh organov». [in Russian]
35. Приказ Министерства здравоохранения РФ от 01.11.2012 №572н «Об утверждении Порядка оказания медицинской помощи по профилю «акушерство и гинекология (за исключением использования вспомогательных репродуктивных технологий)». / Prikaz Ministerstva zdravookhraneniia RF ot 01.11.2012 №572n «Ob utverzhdenii Poriadka okazaniia meditsinskoi pomoshchi po profiliu "akusherstvo i ginekologiia (za iskliucheniem ispol'zovaniia vspomogatel'nykh reproduktivnykh tekhnologii)"». [in Russian]
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1. Wiesenfeld HC, Sweet RL, Ness RB et al. Comparison of acute and subclinical pelvic inflammatory disease. Sex Transm Dis 2005; 32: 400–5.
2. Bevan CD, Ridgway GL, Rothermel CD. Efficacy and safety of azithromycin as monotherapy or combined with metronidazole compared with two standard multidrug regimens for the treatment of acute pelvic inflammatory disease. J Int Med Res 2003; 31: 45–54.
3. Obshchaia zabolevaemost' vzroslogo naseleniia Rossii v 2014 godu. FGBU «Tsentral'nyi nauchno-issledovatel'skii institut organizatsii i informatizatsii zdravookhraneniia» Ministerstva zdravookhraneniia Rossiiskoi Federatsii. URL: http://www.mednet.ru/index.php?option=com_user&view=login&return=aHR0cDovL3d3dy5tZWR... [in Russian]
4. Prakticheskoe rukovodstvo po antiinfektsionnoi khimioterapii. 2-e izd. Pod red. L.S.Strachunskogo, Iu.B.Belousova, S.N.Kozlova. Smolensk: MAKMAKh, 2007. [in Russian]
5. Sweet RL Treatment of acute pelvic inflammatory disease. Infect Dis Obstet Gynecol. 2011; 561909.
6. Haggerty CL, Schulz R, Ness RB. Lower quality of life among women with chronic pelvic pain after pelvic inflammatory disease. Obstet Gynecol 2003; 102 (5): 934–9.
7. Burnett AM, Anderson CP, Zwank MD. Laboratory-confirmed gonorrhea and/or chlamydia rates in clinically diagnosed pelvic inflammatory disease and cervicitis. Am J Emerg Med 2012; 30: 1114–7.
8. Ness RB, Kip KE, Hillier SL et al. A cluster analysis of bacterial vaginosis-associated microflora and pelvic inflammatory disease. Am J Epidemiol 2005; 162: 585–90.
9. Brunham RC, Gottlieb SL, Paavonen J. Pelvic inflammatory disease. N Engl J Med 2015; 372: 2039–48.
10. Oakeshott P, Aghaizu A, Hay P et al. Is Mycoplasma genitalium in women the "New Chlamydia?" A community-based prospective cohort study. Clin Infect Dis 2010; 51: 1160–6.
11. Ross J, Judlin P, Jensen J. International Union against sexually transmitted infections. 2012 European guideline for the management of pelvic inflammatory disease. Int J STD AIDS 2014; 25 (1): 1–7.
12. Ginekologiia: natsional'noe rukovodstvo. Pod red. V.I.Kulakova, I.B.Manukhina, G.M.Savel'evoi. M.: GEOTAR-Media, 2011. [in Russian]
13. CDC. Sexually Transmitted Disease Treatment Guidelines.Pelvic Inflammatory Disease. MMWR. 2015.
14. Wiesenfeld HC, Hillier SL, Meyn LA et al. Subclinical pelvic inflammatory disease and infertility. Obstet Gynecol 2012; 120: 37–43.
15. Tepper NK, Steenland MW, Gaffield ME et al. Retention of intrauterine devices in women who acquire pelvic inflammatory disease: a systematic review. Contraception 2013; 87: 655–60.
16. Hillis SD, Joesoef R, Marchbanks PA et al. Delayed care of pelvic inflammatory disease as a risk factor for impaired fertility. Am J Obstet Gynecol 1993; 168 (5): 1503–9.
17. Clinical Effectiveness Group. UK national guideline for the management of pelvic inflammatory disease 2011. London (UK): British Association for Sexual Health and HIV, 2011.
18. Hillier SL, Kiviat NB, Hawes SE et al. Role of bacterial vaginosis-associated microorganisms in endometritis. Am J Obstet Gynecol 1996; 175 (2): 435–41.
19. Serov V.N., Il'enko L.N. Biologicheskie effekty endotoksina i kliniko-patogeneticheskie reaktsii pri vospalitel'nykh zabolevaniiakh polovykh organov u zhenshchin. Akusherstvo i ginekologiia. 1997; 3: 11–3. [in Russian]
20. Eschenbach DA. Acute pelvic inflammatory disease: etiology, risk factors and pathogenesis. Clin Obstet Gynecol 1976; 19: 147.
21. Bjartling C, Osser S, Persson K. Mycoplasma genitalium in cervicitis and pelvic inflammatory disease among women at a gynecologic outpatient service. Am J Obstet Gynecol 2012; 206 (6): 476.e1-476.e8.
22. Bjornelius E, Anagrius C, Bojs G et al. Antibiotic treatment of symptomatic Mycoplasma genitalium infection in Scandinavia: a controlled clinical trial. Sex Transm Infect 2008; 84 (1): 72–6.
23. Jernberg E, Moghaddam A, Moi H. Azithromycin and moxifloxacin for microbiological cure of Mycoplasma genitalium infection: an open study. Int J STD and AIDS. 2008; 19 (10): 676–9.
24. Workowski KA, Berman SM, Douglas JM, Jr. Emerging antimicrobial resistance in Neisseria gonorrhoeae: urgent need to strengthen prevention strategies. Ann Intern Med 2008; 148: 606–13.
25. Bradshaw CS, Chen MY, Fairley CK. Persistence of Mycoplasma genitalium following azithromycin therapy. PLoS ONE 2008; 3 (11): Article ID e3618.
26. Bondarenko K.R., Bondarenko V.M. Bakterial'nye lipopolisakharidy v patogeneze ginekologicheskikh zabolevanii i akusherskikh oslozhnenii. Zhurn. mikrobiologii, epidemiologii i immunobiologii. 2014; 4: 80–6. [in Russian]
27. Dobrokhotova Iu.E., Dubner N.Iu. Moksifloksatsin v lechenii vospalitel'nykh zabolevanii organov malogo taza. Farmateka. 2005; 2: 68. [in Russian]
28. Lanjouw E, Ouburg S, de Vries HJ et al. 2015 European guideline on the management of Chlamydia trachomatis infections. Int J STD AIDS 2016; 27 (5): 333–48.
29. Kintner J, Lajoie D, Hall J et al. Commonly prescribed β-lactam antibiotics induce C. trachomatis persistence/stress in culture at physiologically relevant concentrations. Front Cell Infect Microbiol 2014; 4: 44.
30. Martinovich A.A., Eidel'shtein M.V., Tsiuman Iu.P., Kozlov R.S. Azitromitsin: sravnenie kachestva in"ektsionnykh lekarstvennykh form original'nogo preparata i ego vosproizvedennykh preparatov. Klin. mikrobiologiia i antimikrobnaia khimioterapiia. 2011; 14 (4): 252–8. [in Russian]
31. Parnham MJ, Erakovic Haber V, Giamarellos-Bourboulis EJ et al. Azithromycin: mechanisms of action and their relevance for clinical applications. Pharmacol Ther 2014; 143 (2): 225–45.
32. Kozlov R.S., Dekhnich A.V. Spravochnik po antimikrobnoi terapii. Smolensk: MAKMAKh, 2013. [in Russian]
33. Klinicheskie rekomendatsii. Akusherstvo i ginekologiia. 4-e izd. Pod. red. V.N.Serova, G.T.Sukhikh. M.: GEOTAR-Media, 2014. [in Russian]
34. Prikaz Ministerstva zdravookhraneniia Rossiiskoi Federatsii ot 24.12.2012 №1502n «Ob utverzhdenii standarta pervichnoi mediko-sanitarnoi pomoshchi pri vospalitel'nykh zabolevaniiakh polovykh organov». [in Russian]
35. Prikaz Ministerstva zdravookhraneniia RF ot 01.11.2012 №572n «Ob utverzhdenii Poriadka okazaniia meditsinskoi pomoshchi po profiliu "akusherstvo i ginekologiia (za iskliucheniem ispol'zovaniia vspomogatel'nykh reproduktivnykh tekhnologii)"». [in Russian]
Авторы
Ю.Э.Доброхотова*, К.Р.Бондаренко, А.С.Дворников
ГБОУ ВПО Российский национальный исследовательский медицинский университет им. Н.И.Пирогова Минздрава России. 117997, Россия, Москва, ул. Островитянова, д. 1
*pr.dobrohotova@mail.ru
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Yu.E.Dobrokhotova*, K.R.Bondarenko, A.S.Dvornikov
N.I.Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation. 117997, Russian Federation, Moscow, ul. Ostrovitianova, d. 1
*pr.dobrohotova@mail.ru