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1 대한요로생식기감염학회지 : 제 6 권제 1 호 2011년 4월 Korean J UTII Vol. 6, No. 1, April 2011 종설 비임균성요도염의최신지견 동국대학교의과대학비뇨기과교실 김기호 서영진 [Abstract] Update of Non-gonococcal Urethritis Ki Ho Kim, Young Jin Seo From the Department of Urology, College of Medicine, Dongguk University, Gyeongju, Korea Urethritis in males not secondary to gonorrhea is classified as non-gonococcalurethritis (NGU). NGU is a common chlamydia-associated syndrome in men. However, Mycoplasma genitalium and Trichomonas vaginalis have been suggested as pathogens that cause NGU. In 20-30% of NGU cases, possible pathogens remain unidentified. Symptoms, if present, include mucopurulent or purulent discharge, dysuria, andurethral pruritis. Culture, nucleic acid hybridization tests, and nucleic acid amplification test are available for the detection of N. gonorrhoeae and C. trachomatis. Treatment should be initiated as soon as possible after diagnosis. Azithromycin and doxycycline are highly effective for chlamydial urethritis. However, infections with M. genitalium respond better to azithromycin. (Korean J UTII 2011;6:25-31) Key Words: Urethritis, Chlamydia trachomatis, Mycoplasma genitalium, Azithromycin, Doxycycline 서 론 요도염은성관계로전파될수있는요로감염질환이다. 요도염의원인균에따라서임균성요도염과비임균성요도염으로나눌수있다. 비임균성요도염의흔한병원균은 Chlamydia trachomatis와 Mycoplasma genitalium 등이있고그외 Trichomonas 교신저자 : 서영진, 동국대학교의과대학비뇨기과교실경북경주시석장동 우 Tel: , Fax: seoyjin@korea.com Received: February 18, 2011 Accepted: March 22, vaginalis, adenovirus, Herpes simplex virus 등이있다. 국내보고에서는비임균성요도염의경우남자환자에한해보건소에서만보고하도록되었으며 2002년이후보고건수가급격히감소하고있다. 1 그러나비임균성요도염의원인균중의하나인클라미디아 (Chlamydia) 감염은매년증가하고있다. 요도의분비물과배뇨통및음경의자극증상등이주증상이지만무증상일수도있다. 진단은전부요도에서백혈구가검출되면요도염으로진단할수있다. 비임균성요도염의치료는병원균의진단이쉽지않기때문에병원균이진단되지않을경우 Chlamydia와 Mycoplasma 등에효과적인항생제로가능한빨리치료를시작하며배양검사나클라미디아검사의결과를기다리지는않는다. 비임균성요도염의경우

2 26 대한요로생식기감염학회지 : 제 6 권제 1 호 2011 년 4 월 azithromycin 등의일차약제가있으나최근이항생제에저항을보이는증례도보고되고있어정확한원인균의진단및치료가필요하리라생각되며이러한비임균성요도염의최신경향에대해서알아보고자한다. 본론 I. 원인균요도염의증상이있는경우임균인지비임균인지를감별해야하고특히클라미디아에대한검사는강력히추천된다. 요도염의증상이있는경우임균과클라미디아에대한검사를시행하고그람음성쌍구균이검출되지않을경우비임균성요도염으로진단할수있으며그원인균으로 15 40% 에서 Chlamydia trachomatis를진단할수있으며 15 25% 는 M. genitalium을진단할수있다. 그외 Trichomonas vaginalis가 1 20%, adenovirus가 2 4%, Herpes simplex virus가 2 3% 정도로보고되고있다. 2 그러나비임균성요도염의 20 30% 는가능한원인균을확인할수없다. 3 비임균성요도염의원인으로서 C. trachomatis가비중이높기때문에비임균성요도염을 C. trachomatis 양성비임균성요도염과 C. trachomatis 음성비임균성요도염으로분류하기도한다. C. trachomatis 음성비임균성요도염의원인균으로가장빈도가높은것은 M. genitalium이며 C. trahomatis 음성인경우 M. genitalium 에가장적합한항생제를쓸경우효과적으로치료할수있었음을보고한문헌도있다. 4-6 Ureaplasma 는 U. parvum (biovar 1) 과 U. urealyticum (biovar 2) 로나누어지며몇몇문헌에서는 U. urealyticum이비임균성요도염의 5 10% 를차지한다는보고가있다. 7 그러나최근 CDC guideline에따르면 M. genitalium외다른 mycoplasma와 ureaplasma는원인균으로지지할만한문헌이부족하다고한다 클라미디아는 M. genitalium보다좀더젊은환자에서많이동정되며두균종이같이혼재되어있는경우는드물다. 12,13 T. vaginalis는인구집단의유형에따라동정률이다르며영국에서는백인이아닌인종 에더많았고 polymerase chain reaction (PCR) 검사법을이용하면검출률을증가시킬수있다. 14 Adenovirus는증상이있는환자의 2 4% 를차지하고종종결막염과연관되어있다. 8,15 Herpes simplex viruses type 1과 2는비임균성요도염과 2 3% 정도에서만연관되어있다. 16 II. 임상양상비임균성요도염의임상증상은요도의분비물, 배뇨통, 음경의자극증상, 혹은무증상일수도있으며진단은전부요도에서백혈구가검출되면요도염으로진단할수있다. 요도염으로진단하기위해서는화농성의고름혹은점액성의요도분비물이있어야하며그람염색요도도말에서 5개이상의백혈구가나오거나첫배뇨소변검체를원심분리하여그람염색한검체에서고배율에서 10개이상의백혈구가나와야한다. 이같은방법으로진단할수없는경우핵산증폭검사법 (nucleic acid amplification test, NAAT) 을이용하여임균과클라미디아를진단해야하고다른가능한원인균도진단해야한다. 17 무증상인경우현미경검사를해야하는지는논란이있다. 18,19 무증상감염자의 30% 정도가치료가늦어지고있으며 또한 single NAAT는약 3% 정도의요도의클라미디아균감염과 5 6% 의 M. genitlaium 감염을놓칠수있다. 18,22,23 NAAT 를이용하지않고현미경검사만시행할경우 NAAT 검사를이용한경우에비해 C. trachomatis 감염인경우 37%, M. gentitalium 감염인경우 62% 에서진단을간과할수있다. 13,24,25 요도도말검사의민감도는마지막으로소변을언제보았는가에도영향을받는다. 특별히정해진최적의시간은없으나일반적으로 2 4시간정도이다. 26 모든환자는임균에대해서배양또는 NAAT를이용하여검사를시행해야한다. 만약 NAAT가양성으로나온다면배양이나다른 NAAT방법을이용하여확진해야한다. 왜냐하면항생제에대한감수성을평가할뿐만아니라낮은빈도로위양성이있을수있기때문이다. 뿐만아니라 NAAT검사조차도 C. trachomatis를 3 10% 에서놓칠수있기때문에 C. tra-

3 김기호외 : 비임균성요도염의최신지견 27 Table 1. Regimens of nongonococcal urethritis Preferred Azithromycin 1g orally in a single dose Doxycycline 100mg orally twice a day for 7 days Alternative Erythromycin base 500mg orally four times a day for 7 days Erythromycin ethylsuccinate 800mg orally four times a day for 7 days Levofloxacin 500mg orally once daily for 7 days Ofloxacin 300mg orally twice a day for 7 days chomatis에대해서반드시의심해야한다. M. genitalium에대한상업적인검사는아직없으며임상에서이검사를해야하는지는좀더토의되어야한다. 전통적인이분법검사는진단에도움이되지않으므로더이상시행해서는안된다. C. trachomatis 혹은 M. genitalium을확인하는방법으로 NAAT 검사법을이용할것을권고하고있으며가능하다면소변이나요도, 자궁경부에서부터채취한검체를사용해야한다. 또한신체검사가필수적이고증상이있는사람에게있어서는더침습적인방법으로채취한검체가진단목적으로필요하다. 가능하다면노출후 NAAT로바로검사해야한다. 모든환자는 HIV과매독에대한검사를같이시행받아야한다. III. 치료비임균성요도염이진단되는대로, 클라미디아에대한검사결과나임균에대한배양검사결과가나올때까지기다릴필요없이치료가시작되어야한다. 요도도말의현미경검사에서도진단되어지지않더라도증상이있는모든환자들은비임균성요도염에대한치료를시작해야한다. 현미경검사를시행할수없는상황이거나결과를믿을수없다하더라도 C. trachomatis와 M. genitalium을다치료할수있는항생제를사용해야하며빈도가높은곳에서는 T. vaginalis 또한치료할수있는약제를사용해야한다. 치료제는 C. trachomatis에매우효과적이면서먹기쉬워야하며낮은부작용과일상 적인생활에지장을최소화할수있는제재이어야한다. 치료를받은사람은재감염의위험성을최소화하기위해모든파트너가치료될때까지금욕해야하며약물복용이끝난시점에서 7일간금욕해야한다. Doxycycline과 azithromycin이일반적으로 C. trachomatis에효과적이고비임균성요도염에도효과적이지만같은용량의 doxycycline과 azithromycin이항상 M. genitalium을치료할수있는것은아니다 이런경우 azithromycin 1g으로즉시치료하는것이효과적이다. 27,28 Azithromycin 1g 한번쓰는것이 7일간의 doxycycline 100mg bid 사용만큼높은치료률을보이고부작용에있어서도차이가없다고하였다 환자의순응도가떨어지는경우에도 azithromycin 1g 한번쓰는것으로치료해야한다. Ofloxacin은 doxycycline 그리고 azithromycin과비슷한효과를보이지만훨씬비싸고여러번사용해야한다. 41,42 Erythromycin은 azithromycin이나 doxycycline에비해효과적이지않고다른약제에비해위장관장애가높다. 43 약제내성은드물지만최근이슈가되고있다 (Table 1). 44,45 IV. 치료후추적관찰증상이지속되거나치료가끝난후에다시재발하는경우재검사를받아야한다. 증상만있고검사실검사에서진단이되지않는경우에는재치료여부를결정하기가쉽지않다. 지속적인회음부및요도, 골반통을호소하거나방광자극증상및사정

4 28 대한요로생식기감염학회지 : 제 6 권제 1 호 2011 년 4 월 Table 2. Recommended regimens of recurrent and persistent urethritis Metronidazole 2g orally in a single dose Tinidazole 2g orally in a single dose plus Azithromycin 1g orally in a single dose (if not used for initial episode) 통을호소하는경우만성전립선염 / 만성골반통증후군을의심해야한다. 적절한치료를받고증상이나징후가없어지고치료받지않은파트너에재노출되지않았다면 C. trachomatis에대한배양검사는일반적인적응증이되지않는다. 죽은미생물에의한위양성을피하기위해치료가되었는지에대한검사는효과적인치료를끝내고 3 4주후에시행한다. C. trachomatis 감염이있는모든사람들은재감염의위험이높기때문에치료 6개월후반복검사를받아야한다. 46 적절한치료후에도감염이지속되는경우는약물복용을정확하게하지않았거나끝내지못한경우, 치료받지않은파트너에게재노출된경우, 새로운파트너로부터의감염, 위양성, 드물지만약물에대한내성등을고려해야한다. 또한지속적인증상을보이는경우다른병원균에의한감염과감염이아닌다른원인을생각해야한다. V. 성적접촉자 / 성파트너의관리증상이처음으로나타나거나증상은없지만진단된날짜로부터 60일이내성관계를가졌던모든파트너는검사및치료를받아야한다. 만약이기간동안파트너가없었다면마지막파트너가검사받고치료받아야한다. 또한여성이거나증상이없는남성은최근에만났던성파트너또는최근 6개월이내의모든파트너는검사및치료를받아야한다. 증상이없는남성의파트너도치료해야하는지에대한직접적인근거는없지만요도염이지속되거나반복감염되는환자에서성파트너가함께치료된후에야치료된다는보고와 NAAT 검사도클라미디아양성자의 3 10% 를놓칠수있으며 M. genitalium 감염이비임균성요도염의 20% 정도를차지하고여성에서질환을일으킬가능성이높다는점을상기한다면무증상파트너도치료를하여야할것이다. 6,12 VI. 지속성 / 재발성비임균성요도염급성요도염의치료후요도염의객관적인증거가없더라도 30 90일이내증상이지속되거나재발하는경우를말하며전체환자의약 10 20% 에서발생한다. 47 치료받지않은새로운파트너에노출되었거나처음시작한약물을복용하지않은경우처음시작했던약물로다시치료할수있다. Doxycycline으로치료했던환자가증상이지속된다면 doxycycline에내성을보이기때문일지도모른다. 또한 U. urealyticum, M. genitalium 및 T. vaginalis가요도염의또다른원인균으로지속성 / 재발성요도염의원인균일수있다. 29 치료는일차약제로사용하지않았다면 azithromycin 1g을사용하고함께 metronidazole 2g을하루한번사용하거나 tinidazole 2g을하루한번사용할것을권장한다 (Table 2). 결론비임균성요도염의원인균을신속하고빨리진단할수있는방법이개발되면서 C. trachomatis뿐만아니라 M. genitalium, T. vaginalis, Herpes simplex virus 그리고 adenovirus 등이원인균으로밝혀지고있다. 비임균성요도염의일차약제는이러한원인균을효과적으로치료할수있는 doxycycline이나 azithromycin을사용할것을권장하고있으며대

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<31395FC0B1C7CFB3AA28C0D3BBF3C1F8B7E1C1F6C4A7B0CBC5E4292E687770> 대한요로생식기감염학회지 : 제 4 권제 1 호 2009년 4월 Korean J UTII Vol. 4, No. 1, April 2009 임상진료지침검토 2007 UK National Guideline on the Management of Non-gonococcal Urethritis 이화여자대학교의학전문대학원비뇨기과학교실윤하나 [Abstract] Hana Yoon