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1 대한요로생식기감염학회지 : 제 7 권제 1 호 2012년 4월 Korean J UTII Vol. 7, No. 1, April 2012 원저 경직장초음파하전립선조직검사후발생한발열을 동반한요로감염의위험인자 제주대학교의학전문대학원가정의학교실, 1 비뇨기과학교실 김현주 김영주 1 허정식 1 [Abstract] The Risk Factors of Urinary Tract Infection with Fever after Transrectal Ultrasonography Guided Biopsy of Prostate Hyeon Ju Kim, Young-Joo Kim 1, Jung-Sik Huh 1 From the Department of Family Medicine, and 1 Urology, School of Medicine, Jeju National University, Jeju, Korea Purpose: Recently, incidence of prostatic cancer has increased due to the development of the prostatic cancer screening test. The common procedure is the transrectal technique, whereby following prophylactic antibiotics, a core biopsy needle is passed through the rectum. Complications of prostate biopsy are perineal tenderness, hematuria, hematospermia, rectal bleeding, fever and sepsis. We estimated the risk factors and pathogens of urinary tract infections after transrectal ultrasound guided biopsy of prostate. Materials and Methods: A retrospective chart review was conducted of patients, who had been treated for urinary tract infection (UTI) after 365 prostatic biopsy between January 2009 and January We analyzed the parameters including past medical history, kind of antibiotics, number of biopsies, pathology, urine culture and blood culture. Results: Hematuria was most common (5.4%), while UTI occurred in 4.9% of the cases. The symptoms of UTI were dysuria and fever. Average admission day was 6.2 days. E. coli was identified in 7 patients. It was observed that higher numbers of biopsies correlated with UTI. The other conditions investigated didn't correlate with complications after biopsies. 교신저자 : 허정식, 제주대학교병원비뇨기과제주제주시아라 1 동번지우 Tel: , Fax: , urohjs@jejunu.ac.kr Received: February 29, 2012 Revised: March 1, 2012 Accepted: March 23, 2012 * 이연구는제주대학교병원연구비로수행되었습니다. 36

2 김현주외 : 경직장초음파하전립선조직검사후발생한발열을동반한요로감염의위험인자 37 Conclusions: We considered that UTI was a rare complication of prostatic biopsy and complications after biopsy were low. A higher number of fragments taken during biopsies showed a correlation with UTI. (Korean J UTII 2012;7:36-42) Key Words: Prostate, Urinary tract infection, Risk factors 서론전립선암의유병율과이로인한사망률은미국뿐만아니라선진국에서연령의증가와전립선암의선별검사인혈청전립선특이항원 (prostate-specific antigen: PSA) 의발견으로인해점차증가하는추세이며미국에서 2010년에 220,000명이전립선암으로새롭게진단되고 30,000명이상이이질환으로인해사망하고있다. 1 우리나라에서평균여명의증가와서구식생활환경과진단기술의발달, 전립선암에대한초기진단을위한노력으로인한전립선암이증가하는추세이다. 2 직장을통한전립선의조직검사는전립선암을진단하는방법으로비교적안전한방법으로알려져있다. 이검사는연령에따른전립선특이항원의증가혹은직장수지검사에서전립선에결절이만져지거나경직장초음파하에저음영의병변을발견하는경우에시행하고있다. 3 전립선조직검사를하는방법은회음부를이용한조직검사혹은직장을통한조직검사를시행하고있으며두방법의진단율이나합병증에는별다른차이를보이지않는다. 4,5 다양하게나타나는합병증을줄이기위해여러가지시술전처치와시술후처방등아직표준화된방법은있지않지만일반적으로전립선조직검사를위해 6시간이상금식을하며검사 1-3시간전에 quinolone 항생제를경구로투약을투약하거나, 검사직전정주로 quinolone 항생제를사용하기도한다. 장에대한전처치로아침에배변을하지못한경우에는관장을하기도한다. 6,7 전립선조직검사는침습적인방법이며이로인해발생되는주요합병증으로는패혈증을포함한요로감염, 급성요폐, 입원을요하는직장출혈등이있으며별다른치료가필요없는혈뇨와단 순한압박을통해지혈이되는직장출혈, 혈정액증등이발생하기도한다. 6,8,9 이러한합병증중요로감염은무증상의농뇨에서부터단순한감염, 열을동반한패혈증혹은쇼크를일으키는경우가있다. 이에저자들은이러한경직장초음파하에전립선조직검사를시행할때발생하는합병증의종류와발생률을알아보고, 아울러요로감염과관련된위험인자를알아보고자하였다. 대상및방법 2009년 1월부터 2012년 1월까지빈뇨혹은야간빈뇨, 요주저등의배뇨증상으로본원외래를방문하거나본원의건강검진혹은개인병원에서우연하게검사한전립선특이항원검사에서연령특이전립선특이항원의참고치보다증가되었거나전립선직장검사에서경결이촉지되거나경직장초음파검사에서저음영의병변이발견된 365명의환자를대상으로경직장초음파하에전립선조직검사를실시하였다. 이들의평균연령은 68.2세 (32-92세) 였으며전립선특이항원은 로평균치는 20.5 ng/ml였다. 전립선의크기는 cc로평균부피는 37.7cc였다 (Table 1). 이들환자중아스피린혹은항응고제를복용하는경우에는약 1주간복용을중단하였고전립선조직검사를하는당일 6시간이상금식을하였으며, 대변을보지않은경우에는관장을오전에실시한이후조직검사를오후에실시하였다. 조직검사전중간요검사, 일반혈액검사를실시하여이상이없는경우에만조직검사를하였다. 경직장초음파하에전립선조직검사를받은환자에서전립선조직검사전항생제처치로는술자에따라차이는있으며시술 3시간전에 quinolone제제인 ciprofloxacin 250mg을경구투여하거나시술직전

3 38 대한요로생식기감염학회지 : 제 7 권제 1 호 2012 년 4 월 levofloxacin을정주로하였으며, 조직검사시에베타딘으로회음부를광범위하게소독한이후직장안을깨끗이소독하였다. 초음파는 7.5 MHz 양면탐침을이용하였으며일회용조직검사침을이용하였다. 전립선조직은전립선의양측소엽의첨부, 중간부, 기저부에서각각조직검사를하는체계적인전립선육분의생검을하였고초음파에서이상소견이나결절이만져지는곳에추가로확대생검을실시하였다. 조직검사중항문출혈이심한경우에는조직검사를더이상시행하지않았다. 시술후직장출혈, 발열, 배뇨장애등다른합병증이없는경우에입원다음날에퇴원을하였다. 결과전립선조직검사이후합병증으로는육안적혈뇨가 20명이었지만특별한조치없이자연적으로모두호전되었다. 급성요폐는 5명으로도뇨관을약 7 일간삽입하였으며 1명에서는조직검사이후암이발견되지않아내시경적전립선절제술을받았다. 직장출혈은 11명으로조직검사직후발견되어수지압박을통한지혈로출혈이멈추었으며수혈을한경우는발생하지않았다. 혈정액증은 1명에서 Table 1. Clinical characteristics of patients undergoing prostatic biopsy Range Mean±SD Age (years) ±9.2 PSA (ng/ml) ±48.2 Volume of prostate (cc) ±18.8 SD: standard deviation Table 2. Incidence of adverse events of prostatic biopsy Complications No. of patients (%) Gross hematuria 20 (54.8) Acute urinary retention 5 (1.3) Urinary tract infection 18 (4.9) Rectal bleeding 11 (3.0) Hematospermia 1 (0.2) Total 55 (100) Table 3. Risk factors for prostatic biopsy Parameter No. of No-UTI patients (%) No. of UTI patients (%) p-value Antibiotics HTN DM CVA Previous biopsy Result of biopsy Oral (ciprofloxacin) 150 (41.1) 10 (2.7) I.V (levofloxacin) 197 (54.0) 8 (2.2) (34.8) 5 (1.4) (60.3) 13 (3.6) + 40 (11.0) 3 (0.8) (84.1) 15 (4.1) + 15 (4.1) 2 (0.5) (91.0) 16 (4.4) (83.8) 13 (3.6) - 41 (11.2) 5 (1.4) Adencarcinoma 118 (32.3) 2 (0.5) Others 147 (40.2) 16 (4.3) (38.2) 7 (1.9) No. of biopsy (57.0) 11 (3.0) UTI: urinary tract infection, HTN: hypertension, DM: diatbetes mellitus, CVA: cardiovascular accident, I.V: intravenous +: presence, -: absence

4 김현주외 : 경직장초음파하전립선조직검사후발생한발열을동반한요로감염의위험인자 39 발견되었다 (Table 2). 요로감염은 18명에서발생하여모두입원치료를하였으며, 이경우귀가하거나귀가이후 2일째발열을동반한요로감염이많았다. 이러한환자의경우요검사와미생물에대한요배양검사, 혈액배양검사를실시하였으며광범위항생제를정주하였다. 배양검사에서항생제에내성이보고되면감수성이있는항생제로변경을하였다. 입원일은 2일에서 20일까지였으나패혈증에의한쇼크가발생한경우는없었다. 전립선조직검사이후요로감염과관련된위험요소를알기위해항생제의경구투여와정주투여, 고혈압, 당뇨, 뇌졸중, 이전에조직검사를한병력유무, 전립선조직검사결과암의유무, 조직검사수등을분석하였으나조직검사수만이통계학적으로유의한결과를나타내었다 (p=0.017) (Table 3). 요배양검사혹은혈액배양검사에서균이동정된경우는 7 명으로모두 E. coli가동정되었으며, 3명에서조직검사결과전립선비대증으로, 2명에서전립선암, 2례에서만성전립선염으로확진되었다. 항생제의감수성검사에서내성이없었던항생제는 amikacin, ce- Table 4. Antibiotics resistance of E. coli Antibiotics No. resistance (N=7) Ampicillin 5 Amoxillin/clavulanic acid 1 Amikacin 0 Aztreonam 3 Cephalothin 3 Cefepime 2 Cefoxitin 0 Gentemicin 4 Imipenem 0 Lefloxacin 6 Meropenem 0 TMP/SMx 5 Cefotaxime 2 Ceftazidime 2 Tobramycin 1 Piperacillin/tazobactam 0 Ciprofloxacin 2 foxitin, imipenam, meropenem, piperacillin/tazobactam 등총 6가지였다. 요로감염에서많이사용하는 qinolones제제인 lefloxacin과 ciprfloxacin은각각 6명과 2명에서내성이발생하였다 (Table 4). 고찰전립선암을진단하는방법으로전립선조직검사는전립선특이항원의발견과건강에대한인식의변화와평균여명의증가로인하여건강검진의수요가지속적으로증가되고있으며미국의경우한해 500,000건이상이시행되고있다. 9 본병원의경우 2001년 1월부터 2007년 9월까지총 275명의전립선조직검사를실시하였으며, 6 이연구에서는 2009년 1 월부터 2012년 1월까지 365명이전립선조직검사를실시하여점차증가하는추세를보였다. 경직장초음파하전립선조직검사는직장을통하는방법이주로이용되지만연령이많거나염증을초래할수있는요도관삽입이된환자나심각한질환을앓고있거나패혈증에쉽게발생할수있는환자에서는회음부를이용한조직검사를더선호한다. 그러나일반적으로이두가지접근방법모두합병증은유사하게발생하고있다 본연구에서는모든환자에게직장을통한전립선조직검사를시행하였다. 전립선조직검사이후합병증으로는쇼크나다발성장기부전등으로인해생명에지장을줄수있는패혈증의증상이있거나항문출혈등으로수혈이나입원치료를요하는경우가 1-2% 정도이고, 특별한치료가필요하지않는혈뇨가 1-84%, 혈정액증이 1-28%, 염증성합병증이 1-4% 이며, 급성요폐, 부고환염, 농양발생등이발생하기도한다 조직검사수가증가함에따라항문에서출혈하는경우가더높게발생하였으며, 16 항문출혈의경우단순한수지압박이나관을이용하기도하고 endoclip을사용하기도한다. 17,18 또한조직검사이후염증을동반한합병증으로는세균뇨, 발열, 요로감염, 패혈증등이발생될수있다. 19,20 본연구에서조직검사후합병증으로는혈뇨가 5.4% 로가장높았지만자연소실되었으며, 요로감염이 4.9%, 직장출혈이 3.0%, 급성요폐가 1.3%, 혈정액증이 0.2% 로나타났으며요로감

5 40 대한요로생식기감염학회지 : 제 7 권제 1 호 2012 년 4 월 염과급성요페를제외하고다른합병증은입원치료가필요없었다. 시술전관장을통한장세척여부는합병증발생과의연관성은없었다는보고도있다. 28,29 저자들의경우검사당일배변을한경우에는장에대한별다른처치는하지않았으며, 배변을하지않은경우만글리세린을이용한관장을실시하였다. 전립선조직검사후요로감염을유발하는주된균주는 E. coli, Enterobacter, Proteus, Klebsiella 등과같은 coilforms이며 Bacteroides, Peptococcus, Peptostreptococcus 등과같은혐기성균에의해발생하기도한다. 21,22 본연구에서는요로감염을유발한균은모두 E. coli 였다. 요로감염을줄이기위해관장실시여부와항생제의종류와투여기간, 조직검사수, 1회용조직검사침을사용하는등다양한시도가되고있으나 % 정도에서요로감염이발생하고있다 전립선조직검사후발생하는요로감염을줄이기위해다양한종류의항생제의투여와투여기간, 종류에대한연구가활발하게진행되고있으나아직논란의여지가있으며일반적으로요로감염예방을위해서세균의 DNA gyrase를억제하는 quinolones제제를경구로약 1-3시간전에투여를하는것은경구투여 1-3시간후에혈중최대농도에다다르기때문이다. 전립선조직검사의요로감염에대한예방적항생제로 quinolone제제가선호되지만최근 quinolones제제에대한내성이생긴균이증가함에따라조직검사전 quinolone제제를투여하였으나발열을동반한요로감염혹은패혈증이발생하기도한다. 6,30,31 Gentamycin과 trimethoprim을병용투여하거나 ciprofloxacin과 tinidazole를병용투여하는경우도있다. 10,30 본연구에서는경구로시술전 ciprofloxacin 을투여하거나시술직전정주로 levofloxacin을투여하였으며이후 2일간경구로 ciprofloxacin을투여하였다. 예방적항생제투여시기에대하여서는아직도논란이많이있으며, 32 Petteffi 등 33 의연구에의하면전립선조직검사에서단한차례 norfloxacin 400mg을복용한환자군보다시술전, 후총 6회이상의 norfloxacin 400mg을복용한군에서요로감염발생이줄어든것으로발표하였다. 그러나최근연구에서항생제의하루요법과단순한한차례의복용이요로감염율을 1% 이하로낮출수있다고하였다 이번연구에서는모두수술전에한차례정주혹은경구로항생제를투여하였으며이후 3일간의경구항생제를지속하였다. 경직장초음파하전립선조직검사의위험요소에대한연구에서요로감염과관련된위험인자로는조직검사수와도뇨관의삽입여부등이었으며연령, 당뇨, 고혈압, 시술전전립선염의병력, 전립선암, 전립선부피, 아스피린복용여부는위험인자가아니었다. 38 본연구에서전립선조직검사이후요로감염과관련된요소로는조직검사의수가연관성이있었으며항생제전처치방법, 고혈압, 뇌졸중의병력, 이전전립선조직검사여부, 전립선암의유무와는관련성이없었다. 결론직장초음파를이용한전립선조직검사는평균여명의증가와건강에대한관심의증가로인해점차증가될것이다. 본연구의연구대상수가적고요로감염이발생한환자수가적은관계로요로감염과의위험요소를직접비교하기는어렵지만전립선조직검사수의증가가요로감염을유발시키는한요소로생각한다. 아울러요배양검사에서 E. coli의 quinolone제제에대한내성이높게나와전립선조직검사전후투여해야하는항생제의선택에대한연구가더이루어져야할것으로생각한다. REFERENCES 1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, CA Cancer J Clin 2010;60: Jang JY, Kim YS. Is protate biopsy essential to diagnose prostate cancer in the older patient with extremely high prostate-specific antigen? Korean J Urol 2012;53: Ramey JR, Halpern EJ, Gomella LG. Ultrasono-

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( )Kju269.hwp 만성세균성전립선염모델흰쥐에서 의항염효과 Anti-inflammatory Effect of Lycopene on Chronic Bacterial Prostatitis Rat Model Cho Hwan Yang, Dong Wan Sohn, Yong-Hyun Cho From the Department of Urology, The Catholic University