대한요로생식기감염학회지 : 제 5 권제 1 호 2010년 4월 Korean J UTII Vol. 5, No. 1, April 2010 종설 클라미디아감염진료지침 동국대학교의과대학비뇨기과교실 김기호 [Abstract] Clinical Guideline of Chlamydia Trachomatis Infection Ki Ho Kim From the Department of Urology, College of Medicine, Dongguk University, Gyeongju, Korea Sexually transmitted diseases (STD) are a major public health problem because their incidence is increasing worldwide despite prevention campaigns and because they raise the risk of HIV infection. Chlamydia trachomatis is the most prevalent bacterial sexually transmitted infection. Several thousands of cases still remain undiagnosed. Chlamydia infections are most often asymptomatic and can cause pelvic inflammatory disease and infertility to women and epididymo-orchitis to men. At present, there is no guideline for management of chlamydia infection in our country so it will help the patients and physicians to treat chlamydia infection and to make the suitable guideline for our country that we know about recent trends of Chlamydia infection guideline. The objective of this study is to know about recent trends of Chlamydia infection guideline focusing on Scottish Intercollegiate Guidelines Network (SIGN) guideline publicated at 2009 and Center for Disease Control and Prevention (CDC) and Canadian guideline publicated at 2006 and World Health Organization (WHO) guideline publicated at 2003. (Korean J UTII 2010;5:40-50) Key Words: Chlamydia trachomatis, Management, Guideline 서 요로생식기내클라미디아와임균감염은그증상이비특이적이거나, 무증상감염이흔하며, 특히클 론 교신저자 : 김기호, 동국대학교의과대학비뇨기과학교실경북경주시석장동 1090-1 우 780-350 Tel: 054-770-8265, Fax: 054-771-0769 E-mail: honda400@dreamwiz.com Received: March 2, 2010 Accepted: March 26, 2010 40 라미디아의경우여성감염자의 80%, 남성감염자의 50% 가무증상감염자이다. 1 이경우정확한진단및적절한치료없이방치되는경우가대부분이며, 치료의지연은심각한후유증을초래할수있고또한성적파트너에게계속적인전파가이루어질수있다. 그러나클라미디아감염에대한진료지침은우리나라에서는아직마련되지않았으며많은나라에서도자기나라실정에맞는진료지침이마련되지못한것이현실이다. 현재까지 2006년 Center for Disease Control and Prevention (CDC) guideline과 2003년 World Health Organization (WHO) 에서나온진료지침이많은나라에서참고하고있
김기호 : 클라미디아감염진료지침 41 Table 1. Symptoms and sign Females Males Neonates and infants Most often asymptomatic Often asymptomatic Conjunctivitis in neonates Vaginal discharge Urethral discharge Pneumonia in infants < 6 months of age Dysuria Urethral itch Lower abdominal pain Dysuria Abnormal vaginal bleeding Testicular pain Dyspareunia Conjunctivitis Conjunctivitis Proctitis (commonly asymptomatic) Proctitis (commonly asymptomatic) 다. 2006년에작성된 CDC와캐나다진료지침, 2009 년 Scottish Intercollegiate Guidelines Network (SIGN) 진료지침을중심으로최근클라미디아감염의진료지침의최근경향이어떻게되는지알아보도록하겠다. 본론병인이되는균은 Chlamydia trachomatis serovars D부터 K까지이며, 전염병예방법 3군에속하고표본감시대상전염병으로전국보건소및 300 여개표본의료기관을중심으로발생현황을파악하고있다. 2006년이후증가양상을보이고있으며 2007 년 3,196명, 2008년 3,501명으로꾸준한증가추세에있다. 2,3 남성의경우클라미디아에대한보균자가많지만증상이없어선별검사로관리하는경우는드물다. 4-6 노출에서감염이발생되기까지잠복기간은보통 2 3주이지만 6주까지길어질수있다. 치료를하지않으면감염은수개월간지속된다. N. gonorrhoeae에감염된사람들은종종 C. trachomatis 와동시감염된다. 5,6 위험인자는클라미디아에감염된사람과성적접촉을한경우, 지난해에새로운성파트너또는 2명이상의성파트너와접촉한경우, 전에성전파성감염이있었던경우, 상처받기쉬운사람 ( 예 ; 마약중독자, 수감자, 성매매종사자, 길거리의젊은이 ) 등이있다. 25세이하의성활동성이활발한모든여성은선별검사를받아야하며증상이없는젊은남성에대해서는선별검사가추천되지않는다. 5,7-16 또한모든임산부여성들은산 전검사시선별검사를받아야하며재감염의위험성이높거나양성인임산부는임신 3기동안선별검사를받아야한다. 17-23 1. 임상양상 50% 에서증상이없으며여성에서는질분비물, 성교통, 하복부통및배뇨통, 비정상적질출혈등이있을수있고질검사시자궁부속기통증과자궁경부에분비물등이있을수있다. 24-40 남성에서는요도분비물과배뇨통이있을수있고부고환염등으로인한고환통과발적이생길수있다 41-43 (Table 1). 1% 미만에서반응성관절염이있을수있으며드물게직장에감염을일으킬수있다. 또한간주위염때문에우측갈비아래부위통증이생길수있다. 44-48 주요합병증으로여성에서는골반염, 자궁외임신, 불임, 만성골반통, 라이터증후군등이있고남성에서는고환-부고환염, 라이터증후군등이있다 (Table 2). 2. 선별검사클라미디아에대한선별검사를시행함으로써생식기계의합병증으로의이환율과사망률를줄일수있으며질병의빈도와유병률을줄일수있다. 16 39 세에서의클라미디아의유병률은남성에서 2.8%, 여성에서 3.6% 이며 25세이하의젊은사람에서의유병률은남성에서 5.1%, 여성에서 6.2% 로높다. 49 클라미디아에양성인사람의성파트너는검사를꼭받아
42 대한요로생식기감염학회지 : 제 5 권제 1 호 2010 년 4 월 Table 2. Major sequelae Females Males Pelvic inflammatory disease Epididymo-orchitis Ectopic pregnancy Reiter syndrome Infertility Chronic pelvic pain Reiter syndrome 야하며클라미디아가의심되고진단되어지지않은사람의성파트너도꼭검사를받아야한다. 12개월이내클라미디아로진단된사람의재감염률도 21 29배로매우높기때문에꼭검사를받아야한다. 50 15세이상 25세이하의여성인경우그보다나이가많은경우에비해클라미디아감염이더흔하다. 51 또한가임이끝난모든여성도클라미디아에대한검사를시행받아야한다. 52-56 6개월후클라미디아감염이있는사람은재감염을예방하기위해서파트너는평가, 검사, 치료및상담을받을필요가있으며, 두파트너의치료가끝날때까지환자및접촉한사람들은성관계를금해야한다. 18,57-60 3. 진단 NAATs (polymerase chain reaction [PCR], transcription-mediated amplification [TMA]) 는배양, enzyme immunoassay (EIA) 그리고 direct fluorescent antibody assay (DFA) 보다더민감하고특이적이다. Standard polymerase chain reaction (spcr), real time polymerase chain reaction (rtpcr), strand displacement amplification (SDA), transcription mediated amplification (TMA), nucleic acid sequence based amplification (NASBA) 의 5가지형태의 NAATs가사용되어지고있다. 클라미디아감염을진단하는데있어 TMA와 SDA가특이도와민감도가높아서추천되어지며 rtpcr은 TMA와 SDA을사용할수없을때사용할수있다. 61 4. 검체수집 NAATs는가능하다면소변이나요도, 자궁경부에서부터채취한검체를사용해야만한다. 혈액과점액은 NAAT의수행을방해할수있으며위음성의결과를보일수있어배양이권장된다. NAAT는연구목적이아닌경우질에서채취한검체는사용할수없다. 목구멍과직장에서채취한검체에서 NAAT를적절하게평가할수없기때문에배양이추천된다. 사춘기나그이후의여성에서는자궁경부에서검체를채취하고수술적으로자궁경부가없다면소변이나요도 swab, 직장 swab, 질 swab을채취하여배양을시행해야한다. 남성인경우첫소변이가장좋으며사춘기이전의여성인경우소변이나질, 직장 swab을채취하여배양을시행한다. 10,62 6개월이하의환아인경우코인두흡입물에서채취한검체로배양을시행한다. 5. 치료검사의결과를기다릴필요없이증상이있는경우바로치료를시행해야한다. 골반염이있는경우불임의위험성이커지기때문에지체없이치료를시행해야하며파트너도바로치료해야한다. 29,63 클라미디아검사에서양성, 클라미디아감염에적합한증상이있는경우, 성파트너의클라미디아감염, 동시감염의가능성 (20 42%) 때문에 N. gonorrhoeae 가진단될때경험적동시치료를시행한다. 치료를받은사람은재감염의위험성을최소화하기위해모든파트너가치료될때까지금욕해야하며약물복용이끝난시점에서 7일간금욕해야한다. 1개의메타분석연구에서 azithromycin 1g 한번쓰는것이 7일간의 doxycycline 100mg 하루 2회사용하는만큼높은치료율을보이고효과적으로치료할수있으며부작용에있어서도차이가없다고하였다. 64-73 환자의순응도가떨어지는경우 azithromycin 1g 한번쓰는것으로치료해야한다. Ofloxacin은 doxycycline 그리고 azithromycin과비슷한효과를보이지만훨씬비싸고여러번사용해야
김기호 : 클라미디아감염진료지침 43 Table 3. Adults (non-pregnant and non-lactating): urethral, endocervical, rectal, conjunctival infection Preferred Alternative Doxycycline 100mg PO bid for 7 days OR Ofloxacin 300mg PO bid for 7 days OR Azithromycin 1g PO in a single dose if poor compliance is Erythromycin 2g/day PO in divided doses for 7 days + expected * OR Erythromycin 1g/day PO in divided doses for 14 days + Tetracyclin 500mg orally, 4 times a day for 7 days Amoxycillin 500mg orally, 3 times a day for 7 days Levofloxacin 500mg orally once daily for 7 days * If vomiting occurs more than 1 hour post-administration, a repeat dose is not required. + Erythromycin dosages refer to erythromycin base. Equivalent dosages of other formulations may be substituted (with the exception of the estolate formulation which is contraindicated in pregnancy). If erythromycin has been used for treatment, a test of cure should be performed 3 4 weeks after completion of therapy. 한다. 74-82 Erythromycin은 azithromycin이나 doxycycline에비해효과적이지않고다른약제에비해위장관장애가높다. 82-86 임신시 erythromycin을사용한다면 erythromycin base가추천되며 estolate를제외하고다른약을대체할수있다. 만약 erythromycin을치료제로사용한다면치료종결후 3 4주에치료에대한테스트를시행해야한다. 임산부에서의 azithromycin에대한한정된자료가있지만많은전문가들은안전한것으로생각한다. 87-92 Doxycycline과 quinolone 제재는임산부와수유중인산모에게는금기이다. 약제내성은드물지만최근이슈가되고있다. 93,94 각각의진료지침의치료부분에서많은차이가나지는않고비슷한치료약제와복용방법을보이지만다른부분도있다. 캐나다및 WHO, CDC, European guideline에서는성인 ( 임산부가아니고수유하고있지않은사람 ) 의요도, 자궁경내막, 직장, 결막감염인경우, doxycycline 100mg 하루두번 7 일간사용혹은 azithromycin 1g 경구하루한번사용을모두추천한다. 대체약제에서약간의차이가있는데공통적인것은 ofloxacin 300mg 하루 2회 7 일간경구투여혹은 erythromycin 2g을 7일간경구투여하는것이며차이점은캐나다에서는 erythromycin 1g을 14일간경구투여를, WHO에서는 amoxicillin 500mg을하루에 3번 7일간사용및 tetracycline 500mg을하루 4번 7일간사용을, CDC에서는 erythromycin ethylsuccinate 800mg을하루 4번 7일간혹은 levofloxacin 500mg을하루한번 7일간사용을, 유럽에서는 ofloxacin 200mg 하루 2번 7일간혹은 roxithromycin 150mg 하루두번 7일간혹은 clarithromycin 250mg 하루두번 7일간사용을추천하고있다 (Table 3). 임산부와모유수유중인엄마의요도, 자궁경내막, 직장감염시공통적으로 amoxicillin 500mg 하루세번 7일간경구투여, erythromycin 2g 7일간경구투여, erythromycin 1g 14일간경구투여, azithromycin 1g 하루한번경구투여를추천하였으며 WHO에서는 erythromycin 2g을 7일간사용, amoxicillin 500mg을하루세번 7일간사용만추천하고있다. CDC에서는 amoxicillin 혹은 azithromycin의사용을추천하고 erythromycin ethylsuccinate 800mg 하루네번 7일간혹은 erythromycin ethylsuccinate 400mg 하루네번 14일간사용을대체할수있다고하였다. 유럽에서는 erythromycin base 2g을 7일간, amoxicillin 500mg 하루세번 7일간및 josamycin 750mg을하루두번 7일간사용을추천하며 erythromycin base 1g을 14일간사용및 erythromycin ethylsuccinate 800mg을하루네번 7일간혹은 eryth-
44 대한요로생식기감염학회지 : 제 5 권제 1 호 2010 년 4 월 Table 4. Pregnant women and nursing mothers: urethral, endocervical, rectal infection Amoxicillin 500mg PO tid for 7 days OR * Erythromycin 2g/day PO in divided doses for 7 days OR *+ Erythromycin 1g/day PO in divided doses for 14 days OR *+ Azithromycin 1g PO in a single dose, if poor compliance is expected Erythromycin ethylsuccinate 800mg orally 4 times a day for 7 days Erythromycin ethylsuccinate 400mg orally 4 times a day for 14 days * If erythromycin or amoxicillin has been used for treatment in nursing mothers, test of cure should be performed 3 4 weeks after the completion of treatment. + Erythromycin dosage refers to the use of erythromycin base. Equivalent dosages of other formulations may be substituted (with the exception of the estolate formulation, which is contraindicated in pregnancy). Gastrointestinal side effects are more severe with erythromycin than with amoxicillin. If vomiting occurs more than 1 hour post-administration, a repeat dose is not required. Note: Test of cure should be performed 3 4 weeks after the completion of treatment in all pregnant women. romycin ethylsuccinate 400mg을하루네번 14일간사용, azithromycin 하루한번사용을대체할수있다고하였다 (Table 4). Erythromycin estolate는임신시금기이며간손상을일으킬수있다. 이렇듯약물치료에있어전체적인추천약은비슷하지만각각의진료지침에따라추천약과대체약에있어약간의차이는있다. 소아에서는각각의진료지침에따른큰차이는보이지않는다. 용량에있어약간의차이가날뿐약제에대해서비슷한추천을하고있다. 결막염을보이는환아인경우클라미디아감염뿐만아니라 N. gonorrhoeae에대해서같이치료를시행해야한다. 25세이하의젊은산모인경우매우높은감염의위험성을지니고있기때문에산전진찰을시행함으로써클라미디아감염을예방할수있다. 신생아시기에클라미디아감염은출생후 5 12일쯤결막염형태로흔히온다. 또한 1 3개월때열이없는비급성폐렴으로올수있다. 결막염시눈꺼풀을외번시켜서 dacron-tipped swab 또는검체 kit 를사용하여얻어진 swab으로부터검체를얻어야하며폐렴인경우비인두에서검체를얻어야한다. Microimmunofluorescence test를시행하기도하지만 널리사용되어지지않으며 IgM 항원이 1:32 이상인경우클라미디아폐렴을강력히시사한다. 45kg 미만의소아의결막염과폐렴인경우 erythromycin 50mg/kg/day로하루네번나누어 10 14일간복용한다. 45kg 이상이고 8세미만이거나 8세이상인소아는 azithromycin과같은성인에서와같은약제와복용법을사용한다. 6주이내의소아에게 erythromycin의사용은 infantile hypertrophic pyloric stenosis (IHPS) 을일으킬수있다. 95-98 다른 macrolide (azithromycin, clarithromycin) 와 IHPS의연관성은알려져있지않지만 erythromycin의사용후득과실에대해서보호자에게충분히설명해야한다. Erythromycin을사용할때 IHPS의증상과징후를관찰하는것이중요하다. 국소항생제만사용하는것은클라미디아감염치료에추천되지않으며전신치료시불필요하다. Silver nitrate와같은점안액을신생아에게쓰는것은엄마로부터의클라미디아감염의전파를예방하지는못하지만임질의전파는예방할수있다. 6. 배우자에게보고증상이처음으로나타나거나증상은없지만진
김기호 : 클라미디아감염진료지침 45 단된날짜로부터 60일이내성관계를가졌던모든파트너는검사및치료를받아야한다. 만약이기간동안파트너가없었다면마지막파트너가검사받고치료받아야한다. 증상이있는남성인경우증상이처음으로나타나기이전 30일이내모든파트너는검사및치료를받아야한다. 또한여성이거나증상이없는남성은최근에만났던성파트너또는최근 6개월이내의모든파트너는검사및치료를받아야한다. 7. 추적관찰적절한치료를받고증상이나징후가없어지고치료받지않은파트너에재노출되지않았다면클라미디아에대한배양검사는일반적으로시행하지않는다. 그러나환자의순응도가떨어지거나대안의치료요법을사용하고있거나모든사춘기이전의어린이와모든임산부는배양검사를받아야한다. 죽은미생물에의한위양성을피하기위해치료가되었는지에대한검사는효과적인치료를끝내고 3 4주후에시행한다. 배양, EIA/ELISA, DNA hybridization은치료를끝내고 2주후에시행하며클라미디아감염이있는모든사람들은재감염의위험이높기때문에치료 6개월후반복검사를받아야한다. 적절한치료후에도감염이지속되는경우는약물복용을정확하게하지않았거나끝내지못한경우, 치료받지않은파트너에게재노출된경우, 새로운파트너로부터의감염, 위양성, 드물지만약물저항등을고려해야한다. 또한지속적인증상을보이는경우다른병원균에의한감염과감염이아닌다른원인을생각해야한다. 재감염시골반염과다른합병증이발생할위험이크다. 치료완결에대한검사로써 PCR은추천되지않으며 3개월에 HIV, B형간염, 매독에대한혈청학적검사를시행해야한다. 결론클라미디아감염은최근다른성전파성질환에비해증가하고있는추세이고증상이없어진단및 치료가늦어져불임과같은심한합병증을유발할수있기때문에적극적인진단및치료가시행되어야한다. 특히임산부인경우출산후소아에게감염을일으켜결막염이나폐렴을일으킬수있으므로클라미디아감염에대한좀더적극적인환자교육과보건당국의관심이필요하며의사및환자또한클라미디아감염에대한적극적인진단및치료가필요하다. 최근에발표된클라미디아감염에대한진료지침은클라미디아감염에대한증상이있다면실험실적진단이나오기전에적극적인치료를할것을권고하고있다. 성인인경우 doxycycline이나 azithromycin 등을사용하여적극적인치료를해야하며임산부인경우는 amoxillin 및 erythromycin과같은안전한항생제를사용하고소아인경우 erythromycin을사용할수있으나득과실을잘생각하여선택해야한다. REFEENCES 1. Stamm WE. Chlamydia trachomatis infections: progress and problems. J Infect Dis 1999;179:380-3 2. Korea Centers for Disease Control and Prevention. 2009 STD guidelines, 2009 (http://stat.cdc.go.kr/kcdchome/jsp/observation/stat/sot/statsot0702list.jsp) 3. Lee JK. Report from a Korea Centers for Disease Control and Prevention 2007. KCDC, 2008;98:127-30 4. Chen MY, Donovan B. Screening for genital Chlamydia trachomatis infection: are men the forgotten reservoir? Med J Aust 2003;179:124-5 5. Andersen B, Olesen F, Moller JK, Ostergaard L. Population-based strategies for outreach screening of urogenital Chlamydia trachomatis infections: a randomized, controlled trial. J Infect Dis 2002;185:252-8 6. Ginocchio RH, Veenstra DL, Connell FA, Marrazzo JM. The clinical and economic consequences of screening young men for genital chlamydial infection. Sex Transm Dis 2003;30:99-106 7. Marrazzo JM, White CL, Krekeler B, Celum CL, Lafferty WE, Stamm WE, et al. Community-based urine screening for Chlamydia trachomatis with a ligase chain reaction assay. Ann Intern Med 1997;127:796-803 8. Marrazzo JM, Whittington WL, Celum CL, Handsfield
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