Review ISSN (Print) / ISSN: X(Online) Korean J Urogenit Tract Infect Inflamm 2013;8(1):1-6 한국인의급성세균성전립선염의특성 박승철 1,2 1 원광대학교의과대학비뇨기과학교

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Review ISSN 1975-7425(Print) / ISSN: 2288-016X(Online) Korean J Urogenit Tract Infect Inflamm 2013;8(1):1-6 한국인의급성세균성전립선염의특성 박승철 1,2 1 원광대학교의과대학비뇨기과학교실, 2 원광대학교원광의과학연구소 Characteristics of Acute Bacterial Prostatitis in Korean Seung Chol Park 1,2 1 Department of Urology, Wonkwang University School of Medicine and Hospital, 2 Institute of Wonkwang Medical Science, Iksan, Korea Prostatitis is the most common urological diagnosis in men younger than 50 years of age and the third most common urological diagnosis in men older than 50 years of age after two major prostatic diseases benign prostatic hyperplasia and prostatic cancer. Acute bacterial prostatitis is a rare disease that accounts for about 5% of prostatitis cases but is relatively easy to diagnose due to its clinical symptoms. This disease constitutes a urological emergence, with obvious signs and symptoms of a urinary tract infection, including dysuria, and urinary frequency. With acute bacterial prostatitis, patients often present with intense suprapubic pain, urinary obstruction, fever, malaise, arthralgia, and myalgia. The most frequent bacteria responsible for causing acute bacterial prostatitis include Escherichia coli, Enterococcus, Proteus, Pseudomonas, Klebsiella, and Serratia. Antimicrobial treatment should be initiated immediately in patients presenting with acute bacterial prostatitis. Initially, parenteral administration of high doses of antibiotics, such as a broad-spectrum penicillin derivatives, a third-generation cephalosporin with or without an aminoglycoside, or a quinolone, are required until the fever and other signs and symptoms of infection subside. After initial improvement, an oral regimen, in particular quinolone, is appropriate and should be prescribed for at least 4 weeks. Keywords: Prostatitis; Bactria; Symptom Copyright 2013, Korean Association of Urogenital Tract Infection and Inflammation. All rights reserved. This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Received: 18 March, 2013 Revised: 8 April, 2013 Accepted: 8 April, 2013 Correspondence to: Seung Chol Park Department of Urology, Wonkwang University School of Medicine and Hospital, 895, Muwangro, Iksan 570-711, Korea Tel: +82-63-859-1334, Fax: +82-63-842-1455 E-mail: sc.park@wonkwang.ac.kr No potential conflict of interest relevant to this article was reported. 서론 전립선염은비뇨기과의사가만나게되는가장흔한질환중의하나이며, 매우중요한질환이다. 전립선염은 50세이하의남성에서가장많이진단되는질환이며, 50세이상의남성에서는전립선비대증, 전립선암에이어세번째로많이진단되 는질환이다. 미국의한연구에의하면전체남성의 11-16% 에서일생동안한차례이상의전립선염증상을경험한다고하였다. 1,2 전립선염은전립선의감염질환, 만성골반동통증후군, 무증상의염증이포함되는질환군이다. 미국보건기구 (National Institutes of Health) 의전립선염의분류 3 는전세계적으로인정받고널리사용되고있다. 카테고리 I은급성세균 1

2 Seung Chol Park Table 1. Classification of prostatitis syndromes Category Name Characteristic I II III IIIA IIIB IV Acute bacterial prostatitis Chronic bacterial prostatitis Chronic prostatitis/chronic pelvic pain syndrome Inflammatory subtype Non-inflammatory subtype Asymptomatic inflammatory Acute bacterial infection Acute urinary tract infection Persistent bacterial infection Recurrent urinary tract infections Characteristic pelvic pains, urinary complaints and sexual dysfunction Absence of other urological disorders Leukocytes in the expressed prostatic fluid, post-prostate massage fluid or seminal fluid No inflammation in the expressed prostatic fluid, post-prostate massage fluid or seminal fluid Asymptomatic patients with inflammatory infiltrates in prostate tissue or seminal fluid specimens evaluated for other indications 성전립선염이고, 카테고리 II는만성세균성전립선염이다. 카테고리 III은만성비세균성전립선염으로, IIIA 염증성만성전립선염과 IIIB는비염증성만성전립선염 / 만성골반동통증후군으로나뉜다. 카테고리 IV는무증상의전립선염으로정의된다 (Table 1). 그중카테고리 I에해당하는급성세균성전립선염은비교적드문질환으로전체전립선염의 5% 에지나지않으며, 대부분환자의임상증상으로진단이가능하다. 4 급성세균성전립선염의원인은요도를통한상행성감염과전립선내로요의역류이다. 급성세균성전립선염을일으키는원인균은 Escherichia coli, Enterococcus, Proteus, Pseudomonas, Klebsiella과 Serratia로알려져있다. 5-8 급성세균성전립선염의치료는혈액배양과요배양을위한검체를얻은후즉각적인광범위항생제투여가치료의주가된다. 대부분의급성세균성전립선염은응급을요하는질환으로항생제의정맥투여가필요하고증상이호전된이후에도 4주가량의경구용항생제투여가필요하다. 그러나급성세균성전립선염이모두같은질환의경과를지니는것은아니다. 일부환자는입원과요로전환이필요없는경미한경과를보이는반면, 다른환자는중환자실입실이필요할정도의중증의경과를거친다. 이종설에서는급성세균성전립선염의위험인자, 원인균, 치료, 질환의자연사에대한외국의문헌과함께국내에서시행된연구결과를분석하여우리나라의급성세균성전립선염의특징을알아보고자하였다. 본 론 1. 급성세균성전립선염의원인일반적으로급성세균성전립선염은상행성요도감염으로인하여발생한다. 후부요도로부터감염된요가사정관이나전립선으로역류되면서발생한다. 요도카테터삽입을포함한방광이나요도의기계적사용이상행성요도감염을야기하는주요원인이다. 8 Lindert 등 9 은요도카테터삽입이전립선의세균감염을일으키는주요위험인자라고하였다. 또한기왕 의전립선조직검사와요역동학적검사가감염을확산시키는주요인자로알려져있다. Ha 등 7 은급성세균성전립선염이발생하기전에기계적조작을한환자에서전립선농양과만성전립선염이훨씬더많이발생한다고하였다. 전립선특이항원의보편화로인하여전립선조직검사가증가함에따라조직검사후발생하는급성전립선염도매우중요하게되었다. Chiang 등 10 의연구에의하면전립선생검후급성전립선염의발생의위험인자는전립선의크기라하였고, 나이, 술전항생제예방적사용, 당뇨, 고혈압, 뇌졸중, 심혈관질환등의기저질환, 항응고제의사용등은연관이없다고하였다. 반면에국내의연구에의하면생검의개수, 술전직장소독여부가감염을일으키는위험인자라고하였으며, 11 다른연구에의하면관장을하지않고외래에서시행하는경우와과거에뇌혈관질환을앓은기왕력이있는환자에서급성세균성전립선염이더많이발생하였다고보고하였다. 12 2. 급성세균성전립선염의원인균급성세균성전립선염을일으키는원인균은 Escherichia coli, Enterococcus, Proteus, Pseudomonas, Klebsiella과 Serratia로알려져있다. 5-8 급성세균성전립선염을일으키는원인균중 Escherichia coli가가장흔한원인균으로알려져있다. 국내의보고도 Escherichia coli가전체급성세균성전립선염의 52-55% 를차지하고있으며 5,7,8 Pseudomonas, Klebsiella, Enterobacter가다음으로많은원인균들이다 (Table 2). 그러나하부요로의기계적조작후발생하는급성전립선염은자연발생한급성전립선염과다른원인균이동정되며항생제내성또한다르게나타난다. 국내의보고에의하면하부요로의기계적조작을한후발생한급성전립선염이 Pseudomonas에의해발생한경우가더많았다 (30.8% vs. 7.9%, p=0.0014). 7,13 또한기계적조작을시행한후발생한급성전립선염에서 ciprofloxacin과 tobramycin에대한내성균주가더많이동정되었다. 7 2006년에대한요로생식기감염학회에서주관한여성의단

한국인의급성세균성전립선염의특성 3 Table 2. Microbial spectrum of patients with acute bacterial prostatitis in Korea Escherichia coli Pseudomonas spp. Klebsiella spp. Enterobacter spp. Streptococcus agalactiae Serratia marcescens Coagulase-negative staphylococcus Enterococci Mixed infection Others Total (n=115) 52.2% (60) 15.7% (18) 9.6% (11) 3.5% (4) 3.5% (4) 1.7% (2) 2.6% (3) 2.6% (3) 4.3% (5) 4.3% (5) Adapted from Ha et al. Int J Antimicrob Agents 2008;31 Suppl 1:S96-101. 7 With prior manipulation (n=39) 46.2% (18) 30.8% (12) 10.3% (4) 0% (0) 7.7% (3) Without prior manipulation (n=76) 55.3% (42) 7.9% (6) 9.2% (7) 3.9% (3) 3.9% (3) 1.3% (1) 2.6% (2) 3.9% (3) 2.6% (2) 5.3% (4) p-value 0.3546 0.0014 0.8567 0.2077 Table 3. Antibiotics susceptibility (%) of pathogens isolated in patients with acute bacterial prostatitis in Korea Ampicillin Amplicillin/sulbactam Piperacillin/tazobactam First-generation cephalosporin Second-generation cephalosporin Third-generation cephalosporin Fourth-generation cephalosporin Ciprofloxacin Ofloxacin Amikacin Gentamicin Tobramycin Imipenem TMP/SMA Escherichia coli (n=60) 31.9 42.3 95.0 70.4 91.9 95.2 96.2 76.2 94.1 98.3 90.5 91.4 100.0 71.4 Other pathogens (n=55) 26.3 30.0 71.4 41.2 53.9 46.7 58.3 68.4 77.8 78.6 65.0 66.7 98.2 60.0 p-vlaue 0.6822 0.4975 0.0157 0.0293 0.0021 <0.0001 0.0030 0.5229 0.2147 0.0029 0.0141 0.0376 0.7882 0.4459 TMP: trimethoprim, SMA: sulfamethoxazole (adapted from Jeon et al. Urology 2003;62:461-6). 11 순방광염의원인균과항생제내성에관한연구의결과에따르면 Escherichia coli에대한 ciprofloxacin의감수성은매우낮은것으로보고되었다. 14 E. coli에의한급성세균성전립선염의연구결과에서도마찬가지로 ciprofloxacin에대한감수성은매우낮은것으로보고되었다. 7 Ampicillin, ampicillin/sulbactam, 1세대 cephalosporin과 trimethoprim/ sulfamethoxazole 에대한감수성은매우낮은반면, 2, 3세대 cephalosporin 과 aminoglycoside 는상대적으로높은감수성을가지고있다. Amikacin은 aminoglycoside 중가장높은감수성을보이는항생제 (98.3%) 이며 tobramycin (91.4%) 과 gentamicin (90.5%) 가그뒤를잇는다 (Table 3). 7 이러한 quinolone계항생제의내성의증가는항생제의오남용으로인하여발생한것으로생각한다. 1999년발표된미국감염병학회 (Infectious Disease Society of America) 의가이드라인에서는 Escherichia coli에대한지역내성이 20% 가넘는항생제는경험적요법의항생제로사용하지말라고권고하고있다. 또한의사는반드시지역의항생제내성에대한정보를반드시 알아야한다고강조하고있다. 15 3. 급성세균성전립선염의증상과진단급성세균성전립선염은드문질환이지만매우중요한하부요로감염질환이다. 급성세균성전립선염은전신의발열을동반하며배뇨증상과저장증상의하부요로증상과급성통증이특징적이다. 환자들은특징적으로빈뇨, 절박뇨, 배뇨통을호소하고지연뇨, 간헐뇨등을포함한배뇨증상을보이며심한경우에는요폐를경험하게된다. 환자는회음부와치골상부의통증을경험하게된다. 대부분의환자에서발열, 오한, 무력감, 오심과구토를포함하는전신증상을지니게되며심한경우에는패혈증으로인한저혈압까지발생할수있다. 16 급성세균성전립선염의증상정도는외래에서단순히경구용약물로만조절될정도의경미한경우부터중환자실입실이필요한중증의경우까지매우다양하게나타난다. 국내의한보고에의하면급성세균성전립선염의증상은발열 68.9%, 통증 48.2%, 배뇨통 66.2%, 요폐 19.2%, 배뇨증상 69.1%, 저장증상 37.0% 의환자에서나타났으며진단당시혈뇨가 57.1% 에서관찰되었으며, 75.1% 의환자에서농뇨가관찰되었다. 7 급성세균성전립선염의증상도기왕의요로계의기계적조작여부에따라다르게나타난다. 기왕의요로계의기계적조작이있었던환자에서발열이더많이나타났고 (79.2% vs. 65.0%, p=0.0005), 통증 (57.7% vs. 44.6%. p=0.0109) 과요폐 (35.4% vs. 13.1%, p=0.0001) 가더많이발생하였다. 7 급성세균성전립선염의진단은대부분임상증상만으로충분히가능하기때문에전립선액검사나 3배분뇨법은진단에필요하지않다. 급성세균성전립선염환자에서직장수지검사는조심스럽게시행해볼수있지만, 전립선마사지는균혈증의확산과패혈증의발생의위험성이있기때문에금기이다. 17 단순요검사에서혈뇨가 51-71% 의환자에서관찰되며, 농뇨가 69-77% 의환자에서관찰된다. 요배양은급성세균성전립선염의원인균을규명하고항생제감수성에대한정보를알수있기때문에매우중요하다. 그러나임상적으로급성전립

4 Seung Chol Park Fig. 1. Treatment algorithm for acute bacterial prostatitis (adapted from Benway and Moon. Urol Clin North Am 2008;35:23-32). 22 선염으로진단된환자에서모두요배양에서양성을보이지는않는다. 국내의한보고에의하면급성전립선염으로진단된환자중 35.4% 의환자에서요배양에서균이동정되었으며요배양에서균이동정된환자에서저장증상이심하고입원기간이길다고보고하였다. 5 혈중전립선특이항원은급성전립선염을진단하는데주요검사는아니지만, 일반적으로중등도이상으로상승하기때문에진단에도움이된다. 7,18,19 즉각적인항생제투여에도불구하고증상의호전이되지않거나전립선농양이의심되는경우에는골반전산화단층촬영이나조심스러운경직장초음파가진단에도움이된다. 20,21 4. 급성세균성전립선염의치료급성세균성전립선염의치료는즉각적인광범위항생제투여와증상완화를위한대증요법이다 (Fig. 1). 22 급성세균성전립선염의항생제치료에대한최근의가이드라인에의하면 cephalosporin이나 fluoroquinolone 의단독요법이나이와 aminoglycoside 와병합요법이추천되고있다. 23 국내의많은기관에서도이가이드라인에맞추어급성세균성전립선염을치료하고있다. 국내의다기관연구에의하면단독요법은 quinolone 요법을가장많이사용하였으며그다음이 3세대 cephalosporin 을사용하였다. 복합요법의경우에는 2, 3세대 cephalosporin과 aminoglycoside의병합요법이가장많이사용되었다. 7 국내의다른연구에서도입원환자의경우에는 cephalosporin 과 aminoglycoside 병합요법이 60% 의환자에서사용되었고그다음에 quinolone 과 aminoglycoside 의병합요법 (14%) 이며 quinolone 단독요법이가장적었다. 외래환자의경우 quinolone 단독요법이가장많이사용되었고그다음이 cephalosporin 단독요법이었다. 8 기왕의요로계의기계조작이있었던환자에서는항생제감수성이낮을것으로 예상되므로 quinolone 단독요법은적절하지못하다. 또한요로계의기계조작이있었던환자에서는 Escherichia coli 외의균이동정될가능성이높고, Escherichia coli 외의균에서 cephalosporin 의감수성은매우낮기때문에 (<60%) 항생제단독요법은제한적으로사용되어야한다. 7 초기의광범위항생제의사용후증상의호전을보이면경구용 quinolone 약물로바꾸어치료를지속한다. 급성세균성전립선염의항생제치료는효과적이며대부분의환자에서 36-48 시간이내에발열이소실되며증상의완화를보인다. 환자의상태가매우경미하고, 합병증이없는경우에는경구용 fluoroquinolone를 10 일사용하면된다. 그러나증상이심한경우에는환자를입원시킨후에 quinolone과 aminoglycoside를병합하거나, 3세대 cephalosporin 등의광범위항생제를경정맥투여해야한다. 환자의상태가안정화되고발열이사라지며요폐가없어지면요배양검사결과에맞추어경구용항생제로교체하여사용해야한다. 항생제치료의기간은명확히정해져있지는않으나환자의증상의경중도에따라결정된다. 한연구에의하면급성세균성전립선염환자의 33% 에서 3개월까지지속적으로세균이관찰되었다고보고하였다. 24 이연구에서는급성전립선염치료로 quinolone 경구용항생제를 6주사용하고재검사를권유하였다. 환자의임상증상이경미한경우에도최소 2주이상의항생제치료가필요하며, 많은경우 4-6 주까지항생제치료가필요하다. 25,26 급성세균성전립선염이있는환자의대부분은전립선의급성염증으로인해배뇨장애가발생한다. 따라서급성세균성전립선염이의심되는환자는반드시잔뇨특정을시행해야한다. 요폐가있는환자에서는작은구경의요도카테터를삽입하거나, 치골상부방광천자를통한카테터삽입이필요하다. 27 잔뇨가 100 ml 이하이나배뇨증상이있는환자에서는알파차단제가증상의완화에도움이된다. 4 그러나급성세균성전립선염에서알파차단제의효과를입증할연구는미흡한상태이다. 또한대변연하제도보존적치료로추천된다. 17 5. 전립선농양전립선농양은흔한질환은아니지만즉각적인치료를요하는중대한전립선의급성감염이다. 전립선농양은면역력이저하된환자나당뇨를가지고있는환자에서주로발생하며, 증상은농양이없는급성세균성전립선염과유사하게나타난다. 28 또한전립선농양은기왕의항생제노출이있었거나의료인등병원에노출된사람에서많이발생한다. 최근항생제의오남용으로인하여병원성세균의변화로인해병원이나기왕의항생제노출이없었던환자에서 methicillin 저항성황색포도상구균에의한전립선농양이보고되기도하였다. 29 골반전산화단층촬영이나자기공명영상이전립선농양의진단에필수적이지만, 경직장초음파가가지는높은민감률과

한국인의급성세균성전립선염의특성 5 상대적저렴한수가로인해사용이증가하고있다. 전립선농양의치료는광범위한경정맥항생제투여와농양의배액이다. 농양의배액은경요도절제술을통한배액이나회음부배액이주치료이다. 경직장초음파를이용한흡인은경요도절제술로인하여생기는문제점들을피할수있는방법이기때문에사용이증가하고있다. 30,31 일부저자들은배뇨장애의해결을위해치골상부천자를통한카테터삽입이필요하다고하였다. 32,33 원인균은급성세균성전립선염과비슷하여 Escherichia coli와 Staphylococcus가가장흔하며 Mycobacterium tuberculosis, Actinomyces, Citrobacter, Bacteroides fragilis, Aeromonas aerophyla, Klebsiella pneumonia 등이보고되었다. 22 6. 전립선조직검사후발생하는전립선염서구화된식생활습관, 평균수명의연장과전립선특이항원사용의보편화로인하여전립선암의발생이증가하고있으며, 이와함께전립선조직검사의수도급증하고있다. 경직장초음파를이용한전립선조직검사의합병증중전립선염과균혈증은가장중한합병증이다. 이러한급성세균성전립선염은조직검사후매우드물게나타나지만, 발생시는즉각적인입원과광범위항생제를경정맥으로투여해야하는심각한질환이다. 조직검사전 quinolone 항생제로적절한전처치를한경우에약 1-2% 의환자에서전립선염이발생한다. 34 전립선조직검사를시행할때요도카테터를가지고있거나세균뇨가있는경우조직검사후급성세균성전립선염이발생할가능성이높기때문에주의깊게관찰하여야한다. 34 시술전전처치의하나인관장의효과는불분명하지만, 시술전적절한예방적항생제를투여하였다면관장은효과가없는것으로알려져있다. 35 감염을일으키는원인균은대부분예방적 quinolone 항생제를비롯한여러약제에내성을보이는 Escherichia coli 가가장흔한원인균이다. 여러약제에내성일보이는 Escherichia coli에의한감염의위험인자는나이, 개발도상국으로의여행과기왕의 quinolone에노출된경우다. 36 전립선조직검사후발생하는급성전립선염의원인이되는 Escherichia coli는대부분 ampicillin, quinolone, cephalosporine에내성을가지고있으며, imipenem과 amikacin에감수성을지니고있기때문에초기에 imipenem 을사용하여야증상의호전시킬수있다. 37 7. 만성전립선염으로진행급성세균성전립선염치료의일차목적은환자의증상을치료하고세균을제거하는것이다. 그러나부적절한치료로인하여원인균을완전히제거하지못하면전립선농양, 급성전립선염의재발, 만성전립선염으로진행하게된다. 7,8 국내의다기관연구에의하면급성전립선염의약 6% 에서전립선 농양이발생하고, 9.5% 에서는증상이재발한다고보고하였다. 또한 8.1-10.1% 의급성전립선염환자에서치료후만성전립선염으로진행한다. 7,8 당뇨, 요로계의기계적조작, 전립선이큰경우와요도카테터를가지고있는환자가나중에만성전립선염으로진행할가능성이많은것으로알려져있다. 8 따라서이러한인자를가지고있는급성전립선염환자는더욱더적극적인치료와추적관찰이필요하며치골상부천자를이용한카테터삽입을통한적극적인요로전환이필요하다. 결론 급성전립선염은비록흔하지는않지만비뇨기과적응급질환중의하나로초기에적절한치료가필요하다. 광범위한항생제투여와증상완화치료가중요하다. 증상이호전되면경구용 quinolone계항생제로바꾸어충분한기간치료하는것이재발과진행을예방하는데중요하다. 또한당뇨와같은기저질환을가지고있거나요로계의기계적조작을받은환자와기왕에항생제에노출되었던환자는질환의경과가중하고진행가능성이높기때문에주의깊은관찰이필요하다. REFERENCES 1. Roberts RO, Lieber MM, Rhodes T, Girman CJ, Bostwick DG, Jacobsen SJ. Prevalence of a physician-assigned diagnosis of prostatitis: the Olmsted County Study of Urinary Symptoms and Health Status Among Men. Urology 1998;51:578-84. 2. Collins MM, Meigs JB, Barry MJ, Walker Corkery E, Giovannucci E, Kawachi I. Prevalence and correlates of prostatitis in the health professionals follow-up study cohort. J Urol 2002;167:1363-6. 3. Krieger JN, Nyberg L Jr, Nickel JC. NIH consensus definition and classification of prostatitis. JAMA 1999;282:236-7. 4. Neal DE Jr. Textbook of prostatitis. In: Nickel JC, ed. Acute bacterial prostatitis. 1st ed. Oxford: Isis Medical Media, 1999. 5. Lee SJ, Lee DH, Park YY, Shim BS. A comparative study of clinical symptoms and treatment outcomes of acute bacterial prostatitis according to urine culture. Korean J Urol 2011;52:119-23. 6. Lee JY, Kim SJ, Ahn HS. The value of serum prostate-specific antigen in the diagnosis and follow-up of acute prostatitis. Korean J Urol 2001;42:800-3. 7. Ha US, Kim ME, Kim CS, Shim BS, Han CH, Lee SD, et al. Acute bacterial prostatitis in Korea: clinical outcome, including symptoms, management, microbiology and course of disease. Int J Antimicrob Agents 2008;31 Suppl 1:S96-101. 8. Yoon BI, Kim S, Han DS, Ha US, Lee SJ, Kim HW, et al. Acute bacterial prostatitis: how to prevent and manage chronic infection? J Infect Chemother 2012;18:444-50.

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