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 From the Department of Urology, Ewha Womans University School of Medicine, Seoul, Korea The main objective is to reduce the number of sexually transmitted infections (STIs) and the complications that can arise in people either presenting with signs and symptoms of an STI, or undergoing investigation for possible infection. Specifically, this guideline offers recommendations on the diagnostic tests, treatment regimens and health promotion principles needed for the effective management of non-gonoccocal urethritis (NGU), covering, the management of the initial presentation, as well as how to prevent transmission and future infection. The recommendation of this guideline may not be appropriate for use in all clinical situations. Decisions to follow these recommendations must be based on the professional judgement of the clinician and consideration of individual patient circumstances and available resources. Key Words: Nongonococcal urethritis, Management, Guideline 2007 년영국비임균성요도염치료가이드라인 2008년 12월에업데이트된영국의 British Association for Sexual Health and HIV Clinical Effectiveness Group이발표한비임균성요도염의영국국립치료지침에대한보고를검토해보고자한다. 요도염은성관계로전파될수있는요로감염질환이다. Chlamydia trachomatis (C. trachomatis) 또는 Mycoplasma genitalium (M. genitlaium) 에감염된남성의 8 37% 는일반적그람염색결과에서는음성 교신저자 : 윤하나, 이화여자대학교의학전문대학원비뇨기과학교실서울시양천구목동 911-1 우 158-710 Tel: 02-2650-5157, Fax: 02-2654-3682 E-mail: wowhana@ewha.ac.kr 134 이나, 요도의분비물이나배뇨통등의증상이있는남성의 50%, 파트너의 3 20% 는 C. trachomatis나 M. genitlaium이검출된다. 비임균성요도염에흔한병원균은 C. trachomatis가 11 43%, M. genitalium 9 25%, Trichomonas vaginalis (T. vaginalis) 1 20%, Adenovirus 2 4%, Herpes simplex virus 2 3% 정도로보고되고있다. Chlamydia는 M. genitalium보다좀더젊은환자에서많이동정되며, 드물게두균종이혼재되어있다. 1,2 비임균성요도염의 30 80% 는 C. trachomatis 혹은 M. genitalium 이동정되지않는다. 2-10 T. vaginalis는인구집단의유형에따라동정률이다른데, 영국에서는백인이아닌인종에더많았고, 더민감한 polymerase chain reaction (PCR) 검사법을이용하면검출률이더증가한다. 11 30세이상의남성 인경우 T. vaginialis가더많이검출된다. 12 Herpes
윤하나 : 2007 UK National Guideline on the Management of Non-gonococcal Urethritis 135 simples viruses type 1과 2는비임균성요도염과 2 3% 정도에서만함께발병한다. 10,13 특별한분비불이없는무증상의요도염은증상성요도염과는다른원인을가지게되어 C. trachomatis나 M. vaginalis는덜검출되며, 무증상의비임균성요도염이세균성질염과관련이있다는보고도있다. 14 한편, C. trachomatis나임균성감염은명백히여성의생식기감염, 특히골반염의원인을제공하며, M. genitalis도가능하다. 1,15-17 그러나, 병원균이음성인 (pathogen negative) 비임균성요도염은여성파트너가골반염 (pelvic inflammatroy disease: PID) 에걸릴수있는지에대해서는의문이다. 18 임상증상비임균성요도염의임상증상은요도의분비물, 배뇨통, 음경의자극증상, 혹은무증상일수도있으며진단은전부요도에서백혈구가검출되면요도염으로진단할수있다. 1) 그람염색요도도말 5 WBC/HPF ( 가장농도가높은곳 5 곳을평균 ) 19 이고, 혹은 2) 첫배뇨소변검체를원심분리하여그람염색한검체에서 10 WBC/HPF ( 가장농도가높은곳 5 곳을평균 ) 위둘중어떤것도가능하며, 도말의질은어떻게검체를받았는지, 그리고검사자간, 검사자내의오차가있을수있다. 20 3) 5mm 플라스틱루프나면봉으로요도의 1cm 안쪽을닦아서검사할수있는데, 둘중어떤것이더나은지에대한데이터는없으나전자가환자에게덜손상을준다 (IV). 4) 원심분리소변검체의 dipstick 검사에서 leukocyte estrase activity 양성과 Chlamydia가검출되면비임균성요도염에상응하는결과이다. 그러나, 어떤것도믿을만한신속한검사방법은없고, 증상이없는환자에서 C. trachomatis의양성예측율은낮다. 7,21 5) 무증상인경우현미경검사를해야하는지는논란이있다. 22,23 무증상감염자의 30% 정도가치료가늦어진다. 22-25 또한, single nucleic acid amplification test (NAAT) 는약 3% 정도의요도의 Chlamydia균감염과 5 6% 의 M. genitalium 감염을놓칠수있다. 26 그러나현미경검사로이런부분을진단할수있다고해도 M. genitalium 감염이골반염같은심각한합병증을일으키는지는아직확실치않다. 한편, 무증상감염자에서현미경검사를빠뜨리면이두병원균중하나라도가지고있는 STD 환자의 77 87% 가량의진단을간과하게된다. 6,27 실제로현미경검사만으로 C. trachomatis와 M. genitalium의진단은각각 37%, 23% 에서놓칠수있다. 따라서무증상의남성에서요도도말의현미경검사는다소정당화되지못하지만 (IIb) 증상이있는남성의경우임균성요도염의진단을위해서라도현미경검사는당연히시행되어야한다. Leukocyte estrase test (1+=positive) 는요도염의진단에다양한민감도를보이는데, 무증상의남성의요도도말에서 Neisseria gonorrhea (N. gonorrhea), C. trachomatis, M. genitalium을진단하는데상당히높은음성예측율 (>96 98%) 을보인다. 한편, 증상이없는남성의 Chlamydia 예측율은 5.1 23.3% 정도로낮다. 7 따라서일반적으로시행하기에는근거가부족하다. 6) 무증상의남성을신체검사하여요도의병원균을진단하기는힘들다. 4 7) 요도도말검사의민감도는마지막으로소변을언제보았는가에도영향을받는다. 특별히정해진최적의시간은없으나일반적으로 2 4시간정도이다. 8) 증상이있으나요도의분비물이없거나요도염이없는경우밤동안의소변으로재검사하거나 (IV), 혹은경험적치료를할수있다 (IV). 경험적치료의대상에는파트너도포함된다. 검사모든환자는 N. gonorrhea검사를해야한다. N. gonorrhea NAAT 양성이면반드시배양으로확인하여야한다. 또한, C. trachomatis도반드시의심하여야한다. NAAT 검사로 3 10% 를놓칠수있
136 대한요로생식기감염학회지 : 제 4 권제 1 호 2009 년 4 월 다. 28,29 M. genitalium의상업적검사기법은아직없으며, 임상에서이검사를적용해야하는지는좀더토의되어야한다. 요로감염이의심되는경우중간뇨의검사를반드시한다. 예를들어환자가배뇨통, 육안적혹은현미경적혈뇨, 야간빈뇨, 빈뇨, 요절박혹은성적접촉이없었던경우에는반드시검사해본다. 전통적이분법검사는진단에별도움이안되므로더이상시행하지않는다 (IV). 치료 1. 일반적권고다음의사항에대해서면으로명확히정보를제공하고숙지시키도록한다. a. 비임균성요도염의원인 - 비감염성원인을포함 - 과환자와파트너의장, 단기합병증에대해 b. 치료의부작용과치료에대한완전한동의의중요성 c. 성파트너의검사와치료의중요성 d. 금욕을하도록권하고그것이힘들경우환자와파트너가완전히치료될때까지콘돔을사용하도록할것 e. 보다안전한섹스에대한권고 f. 어떤추후추적관찰진료에동의할것에대한중요성 2. 치료치료는진단이되는대로가능한빨리, 클라미디아검사나임균배양검사의결과를기다릴필요없이시작한다. 치료로원인균이제거된후에도염증성삼출물이불특정의기간동안지속될수있음을알아야한다. Tetracyclin이일반적으로클라미디아감염에효과적이다. 클라미디아에효과적약이일반적으로비임균성요도염에도효과적이지만같은용량의 tetracycline 사용으로 M. genitalium이항상치료되지는않으며, 이런경우 azithromycin 1g 즉시치료가효과적이다. * 권고약제 (grade of recommendation A) Azithromycin 1g PO single dose (Ib) Doxycycline 100mg twice a say PO for 7 days (Ib) * 대체 (A) Erythromycin 500mg twice daily for 14 days (Ib) Ofloxacin 200mg twice a day or 400mg once a day for 7 days (Ib) 성적접촉자 / 성파트너의관리모든성접촉자들은위험군에속하므로치료하도록하는데, 언제까지의접촉자를치료하는지는임의적이다. 증상이있는남성은 4주전까지의접촉자를치료할것을권한다 (IIb). C. trachomatis 또는 N. gonorrhea가검출되면모든성접촉자는잠재적위험이있다는것을알려야한다. 모든접촉에대한정보는첫방문시얻어지는것이좋은데, 이때 C. trachomatis 또는 N. gonorrhea가검출된경우환자가재방문하지않으면환자에게연락하거나의뢰한쪽 ( 의료진 ) 에연락할수있다는동의도받아야한다 (IV). Chlamydia 요도염에감염된남성과성적접촉을한여성은클라미디아검사결과와무관하게치료받아야한다 (Ib). 증상이없는남성의파트너도치료해야하는지에대해서는직접적근거가없다. 그러나, 결정을내리는데도움이될내용들은있는데, 다음과같다. a. 요도염의영향에대해관찰한비임균성요도염의코호트연구결과는논란이있다. 30 b. 요도염이지속되거나반복감염되는환자는성파트너가함께치료된후에야치료된다는보고들이있다. 31 c. 새로운 NATT 검사도클라미디아양성자의 3 10% 를놓친다. d. 파트너에게서모두클라미디아가발견되는것은아니다.
윤하나 : 2007 UK National Guideline on the Management of Non-gonococcal Urethritis 137 e. 남성의요도에서는그런경우가흔하지않지만, 여성의자궁경부에서는 C. trachomatis가치료없이저절로박멸되기도한다. 32 f. M. genitalium 감염이비임균성요도염의 20% 정도를차지하며, 여성에서질환을일으킬가능성이있다. 1,17 무작위전향적연구는없지만, 병원균은음성인비임균성요도염환자의여성파트너도함께치료하는것이현명하다 (IV). * 이차약제 Moxifloxacin 400mg PO once daily for 10 dyas(iiib) 37 + Metronidazole 400mg twice daily for 5 days (IV) Moxifloxacin은간독성때문에지속성또는재발 성비임균성요도염의 1차치료약제가아니라 2차 약제로권고된다. 38 지속성또는재발성요도염남 성의여성파트너는적절히치료하였다면재치료 할필요는없다. 치료후추적관찰특히 C. trachomatis 양성인남성의치료순응도를확인하기위하여추적관찰이중요하다. 추적관찰은전화인터뷰로도가능하다. 증상이남아있거나약을충분히복용하지않았거나, 치료받지않은파트너와보호장치없이성접촉을한경우에는재방문하여치료를다시받고적절한관리를받도록한다 (IV). 지속성 / 재발성비임균성요도염 - 저자평론 - 본임상지침은영국에서권장되는임상지침이기는하나비임균성요도염의일반적인치료지침의참고로삼아도될것이다. 본임상지침에서는비임균성요도염의일차치료약제로 azithromycin 1g 1 회경구복용을권장한다. 환자의 10 20% 에서지속되거나재발성비임균성요도염이발생하고, 이경우어떤치료든 M. genitalium과 T. vaginialis를함께치료할수있는약제를선택하도록하고있다. 지속성또는재발성비임균성요도염은급성요도염의치료후증상이지속되거나, 30 90일이내에재발하는경우를말하며, 전체환자의약 10 20% 에서발생한다. 33,34 원인균은여러가지이며 M. genitalium이 20 40% 를차지한다. 35 치료는다음과같다. * 일차약제 Aazithromycin 500mg 시작, 이후 250mg for 4days (IIIb) + Metronidazole 400mg twice daily for 5 days (IV) 또는 Erythromycin 500mg four times daily for 3 weeks (Ib) 36 + Metronidazole 400mg twice daily for 5 days (IV) REFERENCES 1. Jensen JS. Mycoplasma genitalium: the aetiological agent of urethritis and other sexually transmitted diseases. J Eur Acad Dermatol Venereol 2004;18:1-11 2. Jensen JS, Bjornelius E, Dohn B, Lidbrink P. Comparison of first void urine and urogenital swab specimens for detection of Mycoplasma genitalium and Chlamydia trachomatis by polymerase chain reaction in patients attending a sexually ransmitted disease clinic. Sex Transm Dis 2004;31(8):499-507 3. Deguchi T, Maeda S. Mycoplasma genitalium: another important pathogen of nongonococcal urethritis. J Urol 2002;167(3):1210-7 4. Falk L, Fredlund H, Jensen JS. Symptomatic urethritis is more prevalent in men infected with Mycoplasma genitalium than with Chlamydia trachomatis. Sex Transm Infect 2004;80(4):289-93
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