Review ISSN 1975-7425(Print) / ISSN: 2288-016X(Online) Korean J rogenit Tract Infect Inflamm 2013;8(2):73-82 카테터연관요로감염 양승옥 중앙보훈병원비뇨기과 Catheter-associated rinary Tract Infection Seung Ok ang Department of rology, VHS Medical Center, Seoul, Korea Catheter-associated urinary tract infection (CATI) is the most commonly occurring nosocomial infection worldwide, accounting for approximately 40% of all hospital acquired infections. A fair number of hospitalized patients undergo insertion of a urinary catheter at some point during their stay, and the use of indwelling urinary catheters appears to be increasing. Instrumentation of the urinary tract is always a high risk factor for CATI. A urinary catheter compromises the normal protective mechanisms of the urinary tract and enables bacterial colonization/biofilm formation on the catheter surface. Bacteriuria may progress toward CATI, which has been associated with increased morbidity, mortality, hospital cost, and duration of stay. nfortunately, many physicians are not aware of appropriate indications for use of indwelling urethral catheters as well as accurate criteria for CATI. These conditions could result in superfluous catheterization, a potential source of CATI, leading to unnecessary use of antimicrobials for treatment of asymptomatic bacteriuria, resulting in emergence of resistant organisms. We discuss the overall view of CATI: definition, pathophysiology, pathogenesis, treatment, and prevention, mainly including descriptions associated with the indwelling urethral catheter. Keywords: Catheters; rinary tract infections Copyright 2013, Korean Association of rogenital 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: 13 March, 2013 Revised: 3 April, 2013 Accepted: 3 April, 2013 Correspondence to: Seung Ok ang Department of rology, VHS Medical Center, 53, Jinhwangdo-ro 61-gil, Gangdong-gu, Seoul 134-791, Korea Tel: +82-2-2225-1493, Fax: +82-2-484-4604 E-mail: seungoc@hanmail.net No potential conflict of interest relevant to this article was reported. 서론 카테터를이용한도뇨는환자관리에있어서다소침습적이기는하나, 여러상황에서흔히사용되는술기이다. 입원환자의 15-25% 가입원중한번쯤은요도카테터를유치하고있었으며, 정규수술을받거나중환자실에재원중인환자의경우는대부분요도카테터를사용해왔다. 1-4 또한, 장기요양시설에서 거주하는환자의약 5% 는지속적으로요도카테터를유치하고있다. 5 한편, 척수손상등에의한일부신경인성방광환자, 수술후일시적인요폐를보이는환자에서카테터를이용한간헐적도뇨가널리사용되고있다. 카테터연관요로감염 (catheter-associated urinary tract infection) 은보건의료에있어서매우중요하고심각한문제이다. 카테터연관요로감염은환자관리에서발생하는모든 73
74 Seung Ok ang. 카테터연관요로감염 Table 1. Criteria for symptomatic urinary tract infection proposed by the National Healthcare Safety Network for catheter-associated urinary tract infection At least one of the following signs or symptoms with no other recognized cause : fever (>38 o C), suprapubic tenderness, costovertebral angle pain or tenderness or For patient 1 year of age, one of fever (>38 o C core), hypothermia (<36 o C core), apnea, bradycardia, dysuria, lethargy or vomiting and rine culture with 10 5 CF/ml with no more than two species of microorganisms or rine culture with 10 3 and <10 5 CF/ml with no more than two species and positive urinalysis (one of positive dipstick for leukocyte esterase or nitrite; pyuria [ 10 WBC/mm 3 or >5 WBC/HPF unspun urine]; microorganisms in Gram stain of unspun urine) CF: colony-forming units, WBC: white blood cells, HPF: high power field. 감염중에가장흔한형태로서미국에서는전체감염중약 40% 에육박하며, 전체요로감염중카테터연관요로감염이차지하는비율도 80% 에달한다. 1,3,6-8 이러한카테터연관요로감염은이환율, 사망률, 병원비, 재원기간을증가시키는요인이되고있다. 2,9-11 게다가세균뇨는불필요한항생제사용을빈번히야기하는데, 이로인해종종다약제내성 (multidrug resistance) 을갖는균주가출현하여다른환자에게전파될수있는위험성도가지고있다. 12,13 본논문에서는카테터연관요로감염의정의, 병태생리및발병기전, 치료그리고현재권장되는예방책들을논의하겠으며, 주로유치요도카테터 (indwelling urethral catheter) 에대한내용을설명하고자한다. 터연관요로감염에대한기준을보면앞서언급한내용을보다상세히기록하고있는데, 이러한기준자체는치료의시기를판단하기위함이아니라감시 (surveillance) 를하면서경과를지켜보기위해만들어진것으로여겨진다 (Table 1). 4,16 신경학적손상때문에간헐적도뇨를이용하는환자들에게카테터연관요로감염이발생할경우일반적인기준에해당하는증상외에도하지강직 (lower limb spasticity), 요실금, 폐쇄로인해원활하지않은도뇨, 자율신경반사부전 (autonomic dysreflexia) 과같은비전형적인증상이나타날수있기때문에참고해야한다. 8,17 2. 카테터연관요로감염의병태생리및발병기전 본 론 1. 카테터연관요로감염의정의 1) 카테터연관세균뇨 (Catheter-associated Bacteriuria) 카테터연관세균뇨는단일카테터를통한소변검체에서 1가지이상의균종이 10 5 colony-forming units/ml 이상검출되는경우를말하는데, 1주일넘게방광카테터를유치하고있는환자대부분에서카테터연관세균뇨가발생한다. 8,14 다행스럽게도카테터연관세균뇨를가지고있는대다수의환자들은무증상이며, 임상적인감염소견도보이지않는다. 15 2) 카테터연관요로감염 카테터연관요로감염의정의는다소이견의여지가있기는하지만, 경요도카테터또는치골상부카테터를유치하고있거나간헐적방광도뇨를하는환자에서유의한카테터연관세균뇨소견뿐만아니라임상적인증상과객관적인감염소견이동반된경우라고할수있으며, 감염에대한다른원인이배제되어야한다. 8 참고적으로카테터가유치된상태가아니라하더라도카테터제거후통상적으로 72시간이내에발생하는경우상기조건을만족하면카테터연관요로감염으로볼수있다. 8 National Healthcare Safety Network가발표한카테 1) 유치요도카테터가요로감염에미치는영향 유치요도카테터는외측으로요도에압력을가하게됨으로써요도점막의혈류를저하시키고, 요로상피점막 (urothelial mucosa) 파열을조장하며, 요도주위선 (periurethral glands) 에서점액이분비되는것을방해한다. 18 또한, 요도카테터가유치된상태에서의배뇨는지속적으로낮은속도의요류가카테터를타고흐르는것이기때문에정상배뇨에서관찰되는감염에대한중요방어기전인요도세척효과를상실하게된다. 18 뿐만아니라, 방광안에서카테터의풍선주위에요저류가발생함으로써방광을완전히비우는것이불가능해지며, 특히환자의움직임이있거나카테터를조작하는경우공기폐색이유발되면서요배출이극도로방해받게된다. 19 카테터연관요로감염을일으키는대다수의세균들은회음부에상재하는세균총이지만, 의료기관종사자의손으로부터감염되는경우도결코무시할수없다. 20 카테터가유치되어있을때세균이요로로침입하여들어오는경로는크게 2가지로나눌수있다. 첫번째는관외경로 (extraluminal route) 로서, 처음에카테터를삽입할때세균이함께들어오거나뒤늦게회음부에있던세균이카테터의외벽을타고올라오는경우를말한다. 21 두번째는관내경로 (intraluminal route) 로서, 이에해당하는세균침입은집뇨주머니 (collection bag) 나폐쇄배출체계 (closed drainage system) 의손상된틈으로부터오염된
Seung Ok ang. 카테터연관요로감염 75 소변이방광으로역류할때발생하게된다. 21 원칙적으로관내경로의감염을피하려면카테터세트의배출도관과집뇨주머니를요도삽입전에연결해놓아야하며, 삽입되어있는동안분리해서는안된다. 15 따라서검체용소변이필요한경우카테터의일방향채취포트 (one-way sampling port) 로부터채취하는것이바람직하다. 15 Tambyah 등 21 이유치요도카테터환자를대상으로시행한전향적연구에서카테터를삽입한후매일집뇨주머니와채취포트로부터동시에소변검체를채취하여정량적배양검사를실시함으로써세균의침입경로를살펴보고자하였다. 이때집뇨주머니에서채취한소변검체보다채취포트에서얻은소변검체에더많은수의세균이검출되는경우는관외경로를통한감염으로간주하였고, 반대의경우는관내경로를통한감염으로간주하였다. 21 그결과카테터연관요로감염이진단된환자의 66% 가관외경로를통한감염으로밝혀졌는데, 그중 18% 는 24시간이내, 48% 는 24시간이후에발생하였다. 21 나머지 34% 는관내경로를통한감염으로밝혀져결론적으로관외경로, 그중에서도카테터를삽입한지 24시간경과후에발생하는카테터연관요로감염이두드러지는것으로나타났다. 21 2) 원인균 요도카테터는유치된기간에따라 30일미만인경우를단기간유치, 30일이상인경우를장기간유치또는만성유치라고간주하는데, 16 요도카테터를단기간유치하고있는경우초기감염은보통단일세균에의하며가장흔한균은 Escherichia coli와다른 Enterobacteriaceae이다. 22,23 이외에도 Pseudomonas aeruginosa, enterococci, Klebsiella, Candida 등이호발하는것으로알려져있다. 21-23 카테터를만성적으로유치하고있는경우에는언제소변을채취하더라도평균적으로 3-5개의균종이검출되며, 그종류에는다양한 Enterobacteriaceae와다른그람음성균, 그람양성균, 진균등이있다. 8 그람양성균중에서 coagulase(-) staphylococci나 enterococci 는흔히검출되기는하지만, 증상을유발시키는감염으로이환되는경우는많지않다. 16 또한, group B streptococci 나 Staphylococcus aureus는상대적으로흔치않다. 16 그람양성구균과진균은대부분관외경로를통해감염되는데반해, 그람음성균은관외경로와관내경로를모두이용하며각경로에따른감염비율은비슷하다. 21 카테터연관요로감염을일으키는원인균분리는항생제내성이높아짐에따라다른양상으로나타나는데, 주로요로감염을포함한이전감염으로인해반복적으로항생제치료를받은기왕력과관련성이높다. 16 Vancomycin 에내성을갖는 enterococci와광범위한 β-lactamase를생산하는 Enterobacteriaceae 가소변검체에서가장빈번히배양되는환경은급성병동이나장기요양시설의환자가유치요도카테터를가지고 있는경우이다. 16 3) 균막형성 (Biofilm Formation) 균막형성은카테터연관요로감염의발병에있어매우중요한문제이다. 방광에카테터가유치된후부터전해질, 유기분자, 숙주단백질로구성된막이카테터벽에생성되는데, 이는각종세균에의한섬모부착 (fimbrial attachment) 의표적이된다. 24,25 부유상태의세균들은섬모의작용과소수성상호작용 (hydrophobic interaction) 을이용하여카테터벽에부착하게되고, 연이은세균증식과세포외기질성분의분비를통해기본적인균막을형성한다. 26 그리고세균들의세포-세포간신호전달체계인쿼럼센싱 (quorum sensing) 을통해복합적인구조와체액통로를갖는성숙한형태의균막을이루면서항상성 (homeostasis) 을유지한다. 26 그런뒤에는균막에숨어있던세균들과균막일부가떨어져나가다른곳으로퍼져나갈수있게된다. 27 결국균막형성은세균이전단력 (shear force) 을회피하게만들고, 항생제작용에대한내성을갖도록하며, 포식작용 (phagocytosis) 을모면하게함으로써세균에게커다란생존이익을준다고봐야한다. 27 요소분해효소 (urease) 를생산하는세균에는 Proteus mirabilis, Proteus vulgaris, Proteus rettgeri, Klebsiella pneumoniae, Morganella morganii, Providencia stuartii 등이있는데, 이들은요소를가수분해시켜암모늄이온을생성함으로써핵형성을일으키는높은 ph를야기시킨다. 14,28,29 소변의높은 ph로인해감염석결정이쉽게침착함에따라균막은결정화되어딱딱한가피를형성하게되고방광감염석이만들어져결국카테터폐쇄를일으키기도한다. 28 3. 카테터연관요로감염의치료 1) 증상이없는카테터연관세균뇨의치료 무증상의카테터연관세균뇨에항생제치료를하는것은증상발생을포함하여이환율호전에도움을주지않고, 연이은감염에내성균이지속적으로나타날우려가크기때문에일반적으로권고되지않는다. 30 한임상연구에서는요도카테터를유치하고있으면서무증상의세균뇨소견을보이는중환자실환자들에대해카테터교체와 3일간의항생제치료를시행받게하였는데, 아무런처치도받지않은대조군과비교했을때요로성패혈증을포함한임상결과에서별차이를보이지않았다. 31 또한, 장기간카테터를유치하고있는환자에서이에대해항생제치료를하는것은무증상세균뇨의재발뿐만아니라증상이있는요로감염의발생도줄여주지못하며, 연속적으로소변을배양하면서살펴본바에의하면항생제에대한내성균만점차증가한것으로알려져있다. 8 간헐적도뇨를하는환자의무증상세균뇨역시항생제치료가임상적인
76 Seung Ok ang. 카테터연관요로감염 이득이별로없고내성균출현빈도만증가시키기때문에추천되지않는다. 30 요도카테터를유치하고있으면서무증상의칸디다뇨를보이는환자에서도항진균제치료를하는것은장기적으로진균뇨를없애는데효과적이지않아임상적인결과를호전시키는데도움을주지못할것으로판단된다. Sobel 등 32 이무증상의칸디다뇨환자를대상으로시행한이중맹검연구에서요도카테터를유치하고있는환자들만분석해보면, 매일 fluconazole 200 mg 과위약을각각 14일간복용시킨후바로시행한소변배양검사에서는 fluconazole 군의칸디다제거율이 52%, 위약군이 25% 로항진균제사용이지지되는듯이보이지만 (p<0.01), 약을중지한뒤 2주가경과한시점에서는 fluconazole군의칸디다제거율이 61%, 위약군이 56% 로나타나항진균제효과가장기적으로는유효하지않은것으로분석됐다 (p=0.66). 에서의항생제사용은내성균의발생을제한하기위해 7일간의치료가권장된다. 8 Peterson 등 34 의연구에따르면, 카테터를유치중인환자의합병요로감염 (complicated urinary infection) 치료에서 levofloxacin 750 mg을 1일 1회 5일간투여한경우와 ciprofloxacin 250 mg을 1일 2회 10일간투여한경우임상적인결과에유의한차이를보이지않았다. 한편, Dow 등 35 의연구에서는간헐적도뇨를이용해배뇨하는척수손상환자의요로감염에 ciprofloxacin 250 mg을 1회 2회 3일간투여한환자군과 14일간투여한환자군을비교하였는데, 3일만투여한환자군에서치료후증상재발률이유의하게더높았다. 이와같이항생제의종류, 약제의용량, 사용일수에따라치료효과및예후의차이를보이므로환자의임상양상, 관련검사소견, 항생제에대한반응등을감안하여각환자에맞게치료일정을정해야할것이라생각된다. 2) 증상이있는카테터연관요로감염의치료 증상을동반하는카테터연관요로감염의항생제치료원칙은기본적인요로감염에서의항생제치료원칙과크게다르지않다. 일차적으로항생제에대한원인균의감수성과환자의임상경과, 순응도, 신기능이고려되어야하고, 선택한항생제가소변으로다량배출되어높은요중농도를유지해야만하며, 이전에투여받은항생제와그에대한내성발생에대해서도파악하고있어야한다. 16 고열, 오심이나구토, 혈역동학적불안정성과같은증상을동반한카테터연관요로감염환자는우선적으로비경구용광범위항생제치료를시작하여야한다. 16 항생제요법은소변배양검사결과가나오면재평가되어야하는데, 항생제에대한초기반응은보통 48-72시간에확인해볼수있다. 16 요도카테터를제거한후발생한요로감염의치료는유치카테터가없는일반환자의요로감염치료와같다고간주하면된다. 16 카테터연관세균뇨환자에서경한증상을보이거나요로감염의기원이불확실한경우항생제치료는소변배양검사결과가나올때까지유보하여정확한항생제를처방하는것이바람직하다. 16 Raz 등 33 에의하면장기요양시설에서만성적으로카테터를유치하고있는환자가임상적으로요로감염이추정될때, 항생제치료전카테터교체를한경우그렇지않은경우보다복합적인세균뇨가감소하고, 고열이내리는시간이단축되었으며, 임상적인재발도감소하여전반적으로요로감염치료에서유리한것으로나타났다. 또한, 소변배양검사결과에따라적절한항생제치료가시작되면단시간내에기대한치료효과를확인할수있으므로다소애매한카테터연관요로감염환자에서는카테터를교체한후배양검사결과를기다려보는것도고려해볼만하다. 카테터연관요로감염에서항생제치료의표준기간은아직명확히정해진바가없지만, 일반적으로카테터가유치된상태 4. 카테터연관요로감염의예방카테터연관요로감염을예방하기위한여러가지방법들이지속적으로제안되고있다. 그중에서는이미환자관리에사용되고있는것들도있지만, 아직한창연구중에있는것들도있다. 한가지유의해야할것은이와관련한많은보고들이증상을동반한요로감염보다는무증상세균뇨에대해연구하여발표한결과라는점이다. 8 1) 카테터의유치결정과유지여부에대한평가 요로카테터를유치하고있는환자의 21-50% 는카테터유치에대한적절한적응증에해당하지않고, 총유치날짜의 33-50% 는불필요하게카테터유치를지속하는것으로평가된다. 28,36,37 또한, 카테터연관요로감염의 17-69% 는적절한감염예방대책을사용했다면예방할수있었을것이라예측된다. 38,39 여러관련진료지침을통해일관되게주장하고있는가장효과적인권고사항은카테터사용을피하거나가능한한빨리제거하는것이다. 40 실제로카테터를일찍제거할수록세균뇨의발생가능성은낮아진다. 41 Healthcare Infection Control Practices Advisory Committee (HICPAC) 에서인정한유치요도카테터의적절한적응증을보면이에해당하는경우가상당히제한적이라는것을알수있다 (Table 2). 4 이와같은사항을체크리스트의형태로만들어사용한다면불필요한카테터사용을줄일수있을것으로판단된다. 카테터연관요로감염의예방을위한상기체계 (reminder system) 의효과에대해서어느정도연구가진행되어왔다. 상기체계는환자에게카테터를거치시킨후일정시간이지나카테터의필요성을재검토하게함으로써카테터유치기간을제한하고자하는것이그목표이다. 상기체계의방법으로우선임상의사나담당간호사가카테터유지여부를매일
Seung Ok ang. 카테터연관요로감염 77 Table 2. Appropriate indications for indwelling urethral catheter use identified by the Healthcare Infection Control Practices Advisory Committee Acute urinary retention or bladder outlet obstruction Need for accurate measurements of urinary output in critically ill patients Perioperative use for selected surgical procedures: - rologic surgery or other surgery on contiguous structures of the genitourinary tract - Anticipated prolonged duration of surgery - Patients anticipated to receive large-volume infusions or diuretics during surgery - Need for intraoperative monitoring of urinary output To assist in healing of open sacral or perineal wounds in incontinent patients Prolonged immobilization (spine injury, multiple traumatic injuries such as pelvic fractures) To improve comfort for end-of-life care if needed 직접상의하게끔하거나사전에정해놓은양식대로카테터 중지처방 을미리발행해두는것을들수있다. 16,40 이러한방법이카테터의사용을줄이고세균뇨의발생을감소시키는데효과가있는것으로알려져있지만, 42 증상을동반한요로감염자체에대한이득에관해서는명확히입증된바가없다. 8,43 상기체계의다른방법으로는환자진료기록에상기스티커를붙여놓는것, 자동으로카테터중지처방이되도록컴퓨터에입력하는것, 관련사항을호출기시스템을통해통보받는것을들수있는데, 일부연구에서는이러한방법들이카테터연관요로감염의발생률도낮추는것으로보고하고있다. 44-46 2) 다른도뇨법으로의대체 유치요도카테터를이용한방광도뇨법을피하고다음과같은방법들로대체하는것도고려해봐야한다. (1) 콘돔카테터 남자에서는외부콘돔카테터를사용해볼수있는데, 만성적인유치카테터에비해요로감염의빈도를낮출수있는것으로알려져있다. 4 Saint 등 47 의연구에따르면, 콘돔카테터를사용한환자의임상결과가유치카테터를사용한경우보다환자의편안함은물론세균뇨, 증상을동반한요로감염, 관련사망률에서모두우위에있는것으로나타났다. 대부분의현재진료지침들은가능하다면콘돔카테터로전환할것을강력히권장하고있다. 3,4,8,48,49 (2) 간헐적도뇨 간헐적도뇨와유치카테터에의한도뇨를비교한대부분의연구들은간헐적도뇨가요로감염의발생을보다줄일수있다는데의견을모으고있다. 16 Hakvoort 등 50,51 이발표한 2개의연구를살펴보면, 부인과수술후간헐적도뇨를시행한경우요도카테터를유치한경우보다환자의선호도증가, 도뇨를시행한기간의단축, 무증상세균뇨와요로감염의감소를보였다. (3) 치골상부카테터를이용한도뇨 치골상부카테터가요도카테터보다세균뇨의빈도를감소시킨다는보고가있고이와관련하여요로감염에서도이득이있을것으로여겨지며, 환자에게더욱편안함을줄수있다는점에서치골상부카테터를이용한도뇨법이다소바람직해 보이기도한다. 16,40 그러나, 치골상부카테터의거치는외과적인시술이필요하며이로인해수반되는합병증을무시할수없고, 치골상부카테터를교체하는일도요도카테터만큼간단하지는않아전문인력이요구되기때문에결코쉽게택할수있는대체도뇨법이아니다. 일부연구에서는치골상부카테터와요도카테터를통한도뇨에서요로감염발생률의차이가없는것으로보고하기도했다. 52,53 결과적으로아직까지는도뇨가필요한환자에서요도카테터보다치골상부카테터의사용이더권장된다고말하기는어렵다고할수있다. 8 3) 카테터관리 손위생은카테터연관요로감염뿐만아니라모든원내감염의예방에서가장중요한개념이다. 54 한연구에서는수술실에서요도카테터를삽입하되일부는무균법 (sterile technique) 으로, 나머지는청결법 (clean/non-sterile technique) 으로시행하였는데, 두군간의세균뇨발생률에유의한차이가없었다. 55 한편, 다른연구에서는수술실에서요도카테터를삽입하는경우와병동또는응급실에서삽입하는경우를비교하였는데, 수술실에서삽입한경우세균뇨의빈도가더낮았다. 21 비록앞선연구에서카테터삽입시엄격한무균술기가굳이필요하지않다는결과가도출되었지만, 병원환경에서는장소에따라상재하는세균이다양하기때문에세균을직접전달시킬수있는의료진의손위생은더욱철저해야한다. 현재각종지침에서도병원에존재하는내성균획득의위험때문에카테터의무균삽입술기를강력히권장하고있다. 3,4,8,48,49 앞서언급했다시피카테터의폐쇄배출체계를유지하는것은카테터연관요로감염의예방과매우밀접한관계가있다. 4,8 Platt 등 56 이입원환자를대상으로시행한연구에따르면, 카테터세트의배출도관과집뇨주머니를미리연결하지않고요도카테터를삽입한환자는미리연결한후삽입한환자보다세균뇨가발생할확률이 2.7배높은것으로조사되었다 (95% confidence interval [CI] 1.3-5.4; p<0.01). 폐쇄배출체계의파괴는카테터를집뇨주머니높이의아래쪽에두거나방광높이의위쪽에위치시키는것과같은정도로세균뇨발생위험을증가시킨다는보고도있다. 57,58 만일폐쇄배출체계가깨지게되면카테터를포함한모든관련기구들을무균상태의
78 Seung Ok ang. 카테터연관요로감염 것으로교체해주는것이바람직하다. 4 대부분의진료지침에서는일정기간마다필수적으로카테터를교체해야한다는의견에동의하지않고있다. 그러나폐쇄배출체계가깨지게되는경우뿐만아니라카테터가막혔을때, 배양검사를위한소변채취전에, 증상을동반하는요로감염의항생제치료전에카테터를교체해야한다는의견이지지를얻고있다. 3,4,8,48,49 방광세척은원래소변배출을원활하게하기위해시행되었는데, 1980년대부터는카테터연관요로감염을예방할목적으로항균제나살균제를포함하여방광을세척하게되었다. 15 하지만항균제나살균제로세척하는이러한시도들이요로감염을줄이는데효과적이라는증거가미약했으며, 폐쇄배출체계를와해시킨다는점에서지지받지못했다. 59-61 이러한방광세척에대한일부연구에서는수술후단기간요도카테터를유치하는경우세균뇨의발생을낮춘다고보고하였으나지속적인항생물질의노출은되려내성균에의한감염을조장하고과도한방광자극을유발하는것으로알려져있다. 62-64 참고로방광을식염수로세척하는행위도전립선이나방광수술후에발생하는출혈과같이카테터폐쇄를일으키는경우를제외하고는권장되지않고있다. 4 요도입구를소독하는것은이론적으로관외경로의세균침입을막음으로써요로감염을예방할수있을것처럼보인다. 그러나베타딘용액, 녹색비누 (green soap) 의살균용액, 다중항생제연고 (polyantibiotic ointment) 로요도입구를소독하는것은카테터연관요로감염을줄여주지못하며, 연구에따라서는되려발생률을증가시키는것으로나타났다. 57,65 요로카테터는환자의움직임에따라요로상피에손상을줄수있으며, 이는세균의침입과감염발생을용이하게한다. 15 Darouiche 등 66 의연구에의하면, 카테터고정장치 (StatLock) 를사용한실험군에서다른장치 ( 테이프, 벨크로, 비고정 ) 를사용한대조군에비해카테터연관요로감염이 45% 감소하였으나통계적으로유의하지는않았다 (p=0.16). 통계적으로유의한차이를보이지않은것은참가자중요로감염이발생한환자의수가적기때문이라추측되며, 66 전반적으로평가했을때카테터고정장치는요로감염을줄이기위해권장될만한방법으로여겨진다. 15 또한, 요로상피손상을줄이기위한다른방법으로는가능한한작은내경의카테터를거치하는것과적절한윤활제사용이추천된다. 3,4,40 하지만살균제가포함된윤활제사용은필수적으로권고되지않는다. 4 이외에도카테터연관요로감염을줄이기위해서는카테터가꼬이는것을피해야하고, 방광높이아래로집뇨주머니를두어야하며, 정기적으로집뇨주머니를비워줌으로써방광에서집뇨주머니로의소변흐름이원활히유지될수있도록해야한다. 3,4,8 4) 카테터선택 (1) 카테터재질 카테터재질은균막형성발생률에영향을미칠수있다. 전자현미경사진으로보면라텍스카테터는실리콘카테터에비해표면이매우울퉁불퉁한데, 이러한표면은세균의부착을용이하게만든다. 67 카테터표면중에서도각구멍주위와제조공정상생기는줄무늬부위가특히균질하지못하다. 15 라텍스성분은생체밖 (in vitro) 에서는독성효과를갖고생체내 (in vivo) 에서는염증유발반응 (proinflammatory reaction) 을일으키는데, 이로인해라텍스카테터를오랫동안유치하는경우용종성방광염 (polypoid cystitis) 에이환되기쉽다. 68-70 실리콘카테터는카테터폐쇄의가능성이더낮다고보고되며, 이는실리콘카테터의내경이더크고가피형성 (encrustation) 의위험이보다낮기때문인것으로여겨진다. 4,16 카테터의재질에따라세균뇨나요로감염의위험도가달라진다고할만한직접적인증거는부족하지만, 8 현재다른재질보다는실리콘카테터가더바람직한것으로받아들여지고있다. 4,15 (2) 카테터디자인 Sun 등 71 이토끼모델을이용하여시행한연구에따르면, 삼엽형 (trefoil) 의횡단면을갖는새로운형태의실리콘카테터를유치한경우일반카테터를유치한것에비해세균뇨의빈도가감소하였고, 요도내시경에서점막손상이더적었으며, 조직병리학적으로도더적은염증소견을보였다. 카테터거치후 4일째삼엽형카테터군에서는 10마리중 3마리가세균뇨소견을보인반면, 대조군에서는 10마리중 8마리가세균뇨를보였으며 (p<0.05), 이러한차이는 8일째에도유의하게유지되었다. 71 삼엽형카테터의입체형태는카테터와요도가접촉하는표면면적을최소화시키기때문에마찰이나손상이감소하고, 요도주위선의점액분비를원활히유지시킨다는장점이있다. 15 물론차후에사람을대상으로하는임상연구가필요하긴하지만, 동물실험결과에비추어볼때단기간카테터유치에있어좋은성과를보일것으로기대된다. (3) 친수성카테터 (Hydrophilic Catheter) 친수성카테터는그특성상환자에게편안함을주고, 요도마찰을줄임으로써점막손상을감소시켜주며, 세균의부착을방해하여집락형성을어렵게만들것이라여겨진다. 한연구에서대다수의환자들이친수성카테터를선호하는것으로나타났지만, 카테터연관요로감염을예방하는데도움이될것이라는의견에대해서는논란이있다. 72 Infectious Diseases Society of America 지침에서는친수성카테터의사용을권장하지않았지만, 8 HICPAC 지침에서는간헐적도뇨를하는환자에서도움이될수있음을시사했다. 4 (4) 항균성분코팅카테터 은이온은세균의필수효소를불활성화시키고피리미딘이합체화 (pyrimidine dimerization) 를촉진시키며세포벽변화
Seung Ok ang. 카테터연관요로감염 79 를야기시키는등다양한살균작용을하는물질이다. 73 Cochrane 연구에서은합금 (silver alloy) 코팅카테터와무증상세균뇨의관계를살펴본조사내용을보면, 라텍스카테터와비교하였을때는세균뇨가유의하게감소한것으로나타났지만 (relative risk [RR], 0.6; 95% CI, 0.5-0.8), 실리콘카테터와비교하였을때는그렇지못했다 (RR, 0.9; 95% CI, 0.5-1.6). 74 Beattie와 Taylor 75 가 11개문헌에대해분석한체계적고찰에서은합금코팅카테터가코팅되지않은일반카테터에비해요로감염을예방하는데유리한측면이있음을확인했지만, 분석된일부문헌들의질적문제와메타분석의어려움을이유로확정적인결과를도출하지는못했다. 현재몇몇주요진료지침에서는은합금코팅카테터가요로감염예방에유용할수있음을언급하고있다. 4,8,49 항생제코팅카테터의경우에서도카테터연관요로감염을감소시킨다는명확한증거를확보하기는어렵다. Cochrane 연구에따르면 nitrofurazone 코팅카테터가일반카테터에비하여 1주까지의세균뇨감소는유의한수준 (RR, 0.5; 95% CI, 0.3-0.8) 을보인반면, 1주후부터는별다른차이를보이지않는것으로나타났다 (RR, 0.1; 95% CI, 0.0-1.3). 74 현재 nitrofurazone 코팅카테터에대한연구정보를가지고요로감염에대한영향을설명하기에는검증력이다소부족하다. 8 다행히도아직까지는 nitrofurazone 코팅카테터가항생제내성을증가시킨다는보고가없으며단기간카테터를유치하는 경우일부분임상적이익을얻을수있을것이라여겨지고있다. 4 이외에도 triclosan, genidine, nitrous oxide, norfloxacin, sparfloxacin, gentamicin, heparin 등을이용한코팅카테터연구가있으며, 대부분요로감염예방에만족할만한결과를보여주지는못하고있다. 15 (5) 그외의카테터 앞서언급한카테터외에도요소분해효소억제, 쿼럼센싱저해, 지방소체 (liposome), 중합체 (polymer), 나노입자 (nanoparticle), 이온영동 (iontophoresis), 진동음향자극 (vibroacoustic stimulation), 세균간간섭 (bacterial interference), 박테리오파지 (bacteriophage) 등을이용한카테터가초기연구중에있거나요로감염예방효과에대한임상시험중에있다. 15 5) 각종주요진료지침 카테터연관요로감염을예방하기위한각종주요진료지침들을보면상당부분의견이비슷하지만권고사안에따라상이한견해를내세우기도한다 (Table 3). 3.4,8,48,49 결 론 각종진료현장에서요로카테터는빈번하게사용되고있으며이로인한요로감염을완전히피하는것은어려운일이다. Table 3. Summary of recommendations from published guidelines Recommendation CDC EA IDSA HICPAC SHEA Limitation of catheter use Evaluate necessity of catheterization Review ongoing need for catheter regularly Evaluate alternative methods of drainage Catheter insertion and selection se of aseptic technique/sterile equipment se of barrier precautions for insertion se smallest bore catheter possible se of silver alloy catheters se of antimicrobial-impregnated catheters se of hydrophilic catheters Catheter maintenance Maintain closed drainage system Replace collecting system if break in asepsis occurs Maintain drainage bag below level of bladder Avoid routine irrigation Diagnostics and antimicrobials Avoid routine urine cultures Avoid use of systemic antimicrobial prophylaxis Do not treat asymptomatic bacteriuria General measures Practice strict hand hygiene Train all persons in catheter insertion and maintenance Written protocols for catheter care CDC: S Centers for Disease Control and Prevention, EA: European Association of rology, IDSA: Infectious Diseases Society of America, HICPAC: Healthcare Infection Control Practices Advisory Committee, SHEA: Society for Healthcare Epidemiology of America, : recommended, N: not recommended, : unresolved (vary according to clinical experience and patient factors), : not discussed. N N N N
80 Seung Ok ang. 카테터연관요로감염 하지만많은임상의사들이적절한사용지침을숙지하지못함으로써충분히예방할수있었던요로감염이발생하게되고그로인한항생제사용도뒤따르게된다. 뿐만아니라배양검사에서세균뇨소견을보이는경우상당히많은환자에서불필요한항생제가투여되고있어내성균의발생과항생제의한계를염려하지않을수없게되었다. 급성병동이나장기요양시설에서카테터를유치중인환자의소변배양으로부터 슈퍼박테리아 라고불리는다약제내성균이검출되는경우를흔히볼수있게된것도걱정스러운일이다. 카테터를사용중인환자에서카테터연관세균뇨와요로감염을명백히구분하여잘못된항생제투여를막아야하고, 가능한한배양에근거한항생제사용이이뤄져야한다. 물론, 그보다앞서카테터연관요로감염이발생하지않도록환자에게요로카테터를사용할만한명백한적응증이있는지정확히따져봐야하고, 지속적인재평가를통해필요하지않은카테터유치는중지시켜야한다. 어떠한카테터를적용할것인지에대해서도상황에맞게결정해야한다. 요로카테터를유치하고있는경우는그렇지않은상태와비교했을때요로감염의측면에서분명한차이를보인다. 카테터로인해우리몸의정상적인보호기전들이제대로작동하지않을뿐만아니라카테터자체가세균침입을조장하는매개체로서작용하기때문에감염에매우불리한상황이되는것이다. 따라서카테터연관요로감염을예방하기위해서는관련병태생리를이해하고감염의우려가있는상황을철저히차단해야한다. 이미이에관해서는많은진료지침이있으므로그것들을참고하여일관성있는예방책을유지해야한다. 카테터연관요로감염을막기위해서는기술적인뒷받침도필요하다. 내성균에대응할수있는항생제개발도중요하지만, 균막형성을차단하는카테터를만드는일이궁극적인해결책이될것이다. 이러한연구에서카테터를평가할때가급적이면무증상세균뇨가아니라요로감염자체에대한예방효과를측정하는데초점을두어실질적인결과가얻어지기를기대해본다. REFERENCES 1. Haley RW, Hooton TM, Culver DH, Stanley RC, Emori TG, Hardison CD, et al. Nosocomial infections in.s. hospitals, 1975-1976: estimated frequency by selected characteristics of patients. Am J Med 1981;70:947-59. 2. Platt R, Polk BF, Murdock B, Rosner B. Mortality associated with nosocomial urinary-tract infection. N Engl J Med 1982;307: 637-42. 3. Lo E, Nicolle L, Classen D, Arias KM, Podgorny K, Anderson DJ, et al. Strategies to prevent catheter-associated urinary tract infections in acute care hospitals. Infect Control Hosp Epidemiol 2008;29(Suppl 1):S41-50. 4. Agarwal RK, Gould CV, Kuntz G, Pegues DA, mscheid CA; Healthcare Infection Control Practices Advisory Committee. Guideline for prevention of catheter-associated urinary tract infections 2009 [Internet]. Atlanta (GA): Centers for Disease Control and Prevention; 2009 [cited 2013 Feb 14]. Available at: http://stacks.cdc.gov/view/cdc/11561/. 5. Smith PW, Bennett G, Bradley S, Drinka P, Lautenbach E, Marx J, et al; SHEA; APIC. SHEA/APIC guideline: infection prevention and control in the long-term care facility, July 2008. Infect Control Hosp Epidemiol 2008;29:785-814. 6. National Nosocomial Infections Surveillance System. National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2004, issued October 2004. Am J Infect Control 2004;32:470-85. 7. Tambyah PA. Catheter-associated urinary tract infections: diagnosis and prophylaxis. Int J Antimicrob Agents 2004;24 (Suppl 1):S44-8. 8. Hooton TM, Bradley SF, Cardenas DD, et al; Infectious Diseases Society of America. Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin Infect Dis 2010;50:625-63. 9. Saint S. Clinical and economic consequences of nosocomial catheter-related bacteriuria. Am J Infect Control 2000;28: 68-75. 10. Givens CD, Wenzel RP. Catheter-associated urinary tract infections in surgical patients: a controlled study on the excess morbidity and costs. J rol 1980;124:646-8. 11. Tambyah PA, Knasinski V, Maki DG. The direct costs of nosocomial catheter-associated urinary tract infection in the era of managed care. Infect Control Hosp Epidemiol 2002;23: 27-31. 12. Schaberg DR, Weinstein RA, Stamm WE. Epidemics of nosocomial urinary tract infection caused by multiply resistant gram-negative bacilli: epidemiology and control. J Infect Dis 1976;133:363-6. 13. oon HJ, Choi J, Park S, Kim CO, Kim JM, ong DE, et al. Outbreaks of Serratia marcescens bacteriuria in a neurosurgical intensive care unit of a tertiary care teaching hospital: a clinical, epidemiologic, and laboratory perspective. Am J Infect Control 2005;33:595-601. 14. Warren JW, Tenney JH, Hoopes JM, Muncie HL, Anthony WC. A prospective microbiologic study of bacteriuria in patients with chronic indwelling urethral catheters. J Infect Dis 1982; 146:719-23. 15. Siddiq DM, Darouiche RO. New strategies to prevent catheterassociated urinary tract infections. Nat Rev rol 2012;9: 305-14. 16. Nicolle LE. rinary catheter-associated infections. Infect Dis Clin North Am 2012;26:13-27. 17. The prevention and management of urinary tract infections
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