Focused Issue J Korean Diabetes 2017;18: Vol.18, No.1, 2017 ISSN 당뇨병과요로감염 김경수차의과학대학교분당차병원내과 Ur

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1 Focused Issue J Korean Diabetes 2017;18: Vol.18, No.1, 2017 ISSN 당뇨병과요로감염 김경수차의과학대학교분당차병원내과 Urinary Tract Infection in Diabetes Kyung-Soo Kim Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea Abstract Urinary tract infection (UTI) is common in patients with diabetes mellitus. Furthermore, UTI is more severe, more often caused by resistant pathogens, and produces worse outcomes in those with diabetes mellitus. Although some patients may have altered clinical signs, symptoms of UTI are similar in patients with or without diabetes mellitus. Treatment depends on severity of systemic symptoms, results of urine culture, and underlying diseases of patients. There are no definite indications to treat asymptomatic bacteriuria in patients with diabetes mellitus. Keywords: Bacteriuria, Diabetes complications, Diabetes mellitus, Pyuria, Urinary tract infections 서론 전세계적으로당뇨병환자가늘어나고있음은주지의사실이다. 감염에취약한당뇨병환자의특성상요로감염또한증가하고있고이에따른의료비용의증가도필연적이어서사회적부담이늘어나고있다 [1-3]. 당뇨병환자에서요로감염의위험이높아지는기전으로면역력저하 [4], 불충 분한혈당조절로인한소변내포도당농도증가 [5], 신경원성방광에의한소변정체 [6] 등이알려져있다. 요로감염은무증상세균뇨 (asymptomatic bacteriuria), 방광염등의하부요로감염, 신우신염등의상부요로감염, 요로성패혈증에이르기까지다양하다. 당뇨병환자에서요로감염은정상인에비해기종성신우신염 (emphysematous pyelonephritis), 신장농양, 신유두괴사 Corresponding author: Kyung-Soo Kim Department of Internal Medicine, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam 13496, Korea, kks982@hanmail.net Received: Feb. 3, 2017; Accepted: Feb. 9, 2017 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright c 2017 Korean Diabetes Association 26 The Journal of Korean Diabetes

2 김경수 등의더심각한합병증을발생시킬위험이높다 [7,8]. 또한의료관련 (healthcare-associated) 요로감염의위험이높고 [9,10] 내성균주에의한요로감염위험도증가시키므로 [11-14] 주의를요한다. 본글에서는당뇨병환자의요로감염에대해살펴보고자한다. 본론 1. 당뇨병환자에서요로감염의기전당뇨병환자에서요로감염의위험을높이는다양한기전이알려져있다 [15,16]. 우선소변내의높은포도당농도가세균의성장을촉진시킬수있을것이다 [5,17]. 하지만여러연구에서당화혈색소수치와요로감염사이의관련성은발견되지않았고 [18,19], 기전상소변내포도당농도를높이는 sodium-glucose co-transporter 2 (SGLT2) 억제제또한요로감염의위험을높이지않아추가연구가필요하다 [20]. 하지만신장실질내포도당농도가높은것은세균의성장, 증식에유리하고이로인해신우신염및신장합병증의위험을높인다 [21]. 당뇨병환자에서다양한면역체계의장애역시요로감염의위험을높이는요소로작용한다 [4,22]. 무증상세균뇨가있는당뇨병환자의소변내인터루킨-6와인터루킨-8이무증상세균뇨가없는당뇨병환자보다낮게측정되었다는연구도있었다 [23]. 자율신경계이상으로인한신경원성방광은방광내잔뇨량을늘리고이는세균의성장및증식에좋은환경을제공하여요로감염의위험을높인다 [6,24]. 2. 당뇨병환자에서요로감염의유병률당뇨병환자는정상인에비해요로감염이흔하게발생하지만당뇨병의종류, 성별및요로감염의종류에따라다양하게나타난다. 2005년네덜란드에서제1형당뇨병환자 705명, 제2형당뇨병환자 6,712명, 정상인 18,911명을전향적으로조사한결과정상인과비교한상대위험도가제1 형당뇨병환자에서 1.96배, 제2형당뇨병환자에서 1.24배높게나타났다 [25]. 덴마크에서 353명의당뇨병환자를포함한 10,000명이상의정상인을대상으로한코호트연구에서는당뇨병환자의요로감염위험이정상인보다 3배이상높게나타났다 [26]. 최근영국 1차진료연구데이터베이스 (The UK General Practice Research Database) 를활용하여제2형당뇨병을가진환자와정상인을비교한결과요로감염은당뇨병환자에서 46.9/1,000인년 (person-year) 으로정상인의 29.9/1,000인년보다높게나타났다 [27]. 또다른연구에서 70,000명가량의제2형당뇨병환자를조사한결과 1년간 8.2% 가요로감염으로진단받았다 ( 여자 12.9%, 남자 3.9%) [28]. 당뇨병환자에서무증상세균뇨의유병률은 8~26% 이다 [5,21]. 한메타분석에따르면정상인의 4.5% 와비교하여당뇨병환자의 12.2% 에서무증상세균뇨를보인다고하였다. 또한남성보다여성에서흔하고당뇨병의유병기간이길수록흔했지만당화혈색소를기준으로한혈당조절상태와는관련이없었다 [18]. 3. 당뇨병환자에서요로감염의위험인자정상인과같이요로감염의과거력과최근의성관계는당뇨병환자에서도요로감염의위험인자이다 [15]. 하지만당뇨병환자에서요로감염의위험이 2배이상증가하는이유가명확히밝혀져있지는않은데이론적으로는방광기능이상과불충분한혈당조절로인해요로감염의위험이증가할것으로생각되지만실제연구결과는이를뒷받침하지못했다 [29]. 방광기능이상에의한잔뇨량의증가나단백뇨의존재도요로감염과명확한관련성을보여주지못했고 [6,18], 당화혈색소수치또한요로감염의위험과관련없다는보고가많았다 [18]. 사우디아라비아에서진행된한연구에서는당뇨병환자중여성 ( 비교위험도 [relative risk, RR] = 6.1), 고혈압 (RR = 1.2), 인슐린치료 (RR = 1.4), 체질량지수 30 kg/m 2 이상 (RR = 1.72), 신증 (RR = 1.42) 이있는환자에서요로감염의위험이높았다 [30]. 하지만 27

3 Focused Issue 당뇨병과요로감염 연구디자인과포함된지표에따라상이한결과를나타내기때문에아직까지는정확한위험인자가확립되어있지는않다. 4. 당뇨병환자에서요로감염의원인균당뇨병환자에서도요로감염의흔한원인균은정상인에서와같이대장균 (Escherichia coli) 과 Klebsiella spp. 와같은기타장내세균 (Enterobacteriaceae), Proteus spp, Enterobacter spp, Enterococci 등이다 [16,31]. 다만당뇨병환자에서요로감염이흔하고이로인한항생제사용이많아지면서 extended-spectrum β-lactamase 양성 Enterobacteriaceae, fluoroquinolone 내성균, carbapenem 내성 Enterobacteriaceae, vancomycin 내성 Enterococci 등과같은내성균주에의한요로감염의위험이높다는점에주의해야한다 [11-14]. 진균또한당뇨병환자에서요로감염의원인균이될수있다 [32]. 5. 당뇨병환자에서요로감염의진단요로감염의증상이있는모든당뇨병환자에게요로감염가능성을생각해보아야한다. 하부요로감염의증상은빈뇨, 절박뇨, 배뇨통, 치골상통증등이고상부요로감염의증상은늑골척추각통증 / 압통, 발열, 오한등이있다. 당뇨병환자는이러한증상이더심하게나타나거나약간다른증상을보이기도하는데 [7] 우리나라의한연구에따르면당뇨병환자는늑골척추각통증이나옆구리통증을더적게호소하였다 [33]. 심지어당뇨병환자는요로감염과함께저혈당혹은고혈당, 케톤산혈증등으로발현하는경우도있다 [34]. 요로감염이의심이되면진단을위해중간뇨에서백혈구를확인해야한다. 소변내백혈구는농뇨 (pyuria) 가있을때흔히동반되기때문이다. 요로감염의진단및치료를위해요배양검사를반드시시행해야하는데여성환자는중간뇨배양검사에서 10 5 colony-forming units (CFU)/mL 이 상의균이배양되는경우, 남성환자는 10 4 CFU/mL 이상의균이배양되는경우진단이가능하다. 무균처리된카테터를통해얻은소변이라면 10 2 CFU/mL 이상의균만배양되어도진단할수있다. 장기간도관을가지고있거나간헐적으로도관을통해소변을뽑아내는환자는 10 3 CFU/mL 이상의균이배양될경우진단할수있다. 요배양검사에서요로감염의기준은충족하나요로감염의증상이없는경우무증상세균뇨로진단한다 [16]. 6. 당뇨병환자에서요로감염의치료당뇨병환자에서요로감염의치료는당뇨병이없는환자의치료와다르지않다. 의심되는균에치료효과가있는항생제를사용하고동반되어있는대사이상을교정하는것이중요하다. 하지만내성균에의한요로감염의위험이높으므로항생제선택에주의를요한다. 무증상세균뇨의경우현재까지당뇨병환자에서치료를해야하는근거는명확하지않다 [35]. 7. 당뇨병환자에서요로감염의예후당뇨병환자에서요로감염의예후는당뇨병이없는환자보다좋지않다 [5,36]. 요로감염환자에서당뇨병은오랜입원기간, 질소혈증 (azotemia), 패혈증, 패혈성쇼크와관련되어있고, 사망률또한 65세이상당뇨병환자에서같은연령대정상인의요로감염에비해 5배가량높다 [7]. 네덜란드의한연구에따르면정상여성과비교하여당뇨병여성에서재발 (7.1% vs. 15.9%) 및재감염 (2.0% vs. 4.1%) 또한흔하다고하였다 [37]. 8. 당뇨병환자에서당뇨병치료와요로감염의위험 SGLT2 억제제로치료받는당뇨병환자의경우현재까지발표된연구결과로는요로감염의위험을유의하게증가시키지는않았다 [20]. 하지만일부약제에서요로감염의 28

4 김경수 발생이높은경향을보였고연구기간도제한적이어서향후장기간의대규모연구가필요하겠고요로감염의과거력이있던환자에게사용할경우신중하게치료여부를결정해야하겠다. 결론 당뇨병환자에서요로감염는흔하다. 또한정상인의요로감염와비교하여더심각하고, 저항성균주에의한감염이많으며예후또한좋지않기때문에당뇨병환자의요로감염에는주의를기울여야한다. 당뇨병환자에서요로감염의치료는정상인과같은기준으로하지만감염의중증도와배양결과에따라적절한항생제선택이필요하다. 무증상세균뇨는당뇨병환자에서도치료의근거가명확하지않고불필요한치료로인해내성균의발생을야기할수있으므로치료에주의를요한다. REFERENCES 1. Joshi N, Caputo GM, Weitekamp MR, Karchmer AW. Infections in patients with diabetes mellitus. N Engl J Med 1999;341: Shah BR, Hux JE. Quantifying the risk of infectious diseases for people with diabetes. Diabetes Care 2003;26: Boyko EJ, Fihn SD, Scholes D, Abraham L, Monsey B. Risk of urinary tract infection and asymptomatic bacteriuria among diabetic and nondiabetic postmenopausal women. Am J Epidemiol 2005;161: Delamaire M, Maugendre D, Moreno M, Le Goff MC, Allannic H, Genetet B. Impaired leucocyte functions in diabetic patients. Diabet Med 1997;14: Fünfstück R, Nicolle LE, Hanefeld M, Naber KG. Urinary tract infection in patients with diabetes mellitus. Clin Nephrol 2012;77: Truzzi JC, Almeida FM, Nunes EC, Sadi MV. Residual urinary volume and urinary tract infection--when are they linked? J Urol 2008;180: Kofteridis DP, Papadimitraki E, Mantadakis E, Maraki S, Papadakis JA, Tzifa G, Samonis G. Effect of diabetes mellitus on the clinical and microbiological features of hospitalized elderly patients with acute pyelonephritis. J Am Geriatr Soc 2009;57: Mnif MF, Kamoun M, Kacem FH, Bouaziz Z, Charfi N, Mnif F, Naceur BB, Rekik N, Abid M. Complicated urinary tract infections associated with diabetes mellitus: pathogenesis, diagnosis and management. Indian J Endocrinol Metab 2013;17: Lee JH, Kim SW, Yoon BI, Ha US, Sohn DW, Cho YH. Factors that affect nosocomial catheter-associated urinary tract infection in intensive care units: 2-year experience at a single center. Korean J Urol 2013;54: Datta P, Rani H, Chauhan R, Gombar S, Chander J. Health-care-associated infections: risk factors and epidemiology from an intensive care unit in Northern India. Indian J Anaesth 2014;58: Schechner V, Kotlovsky T, Kazma M, Mishali H, Schwartz D, Navon-Venezia S, Schwaber MJ, Carmeli Y. Asymptomatic rectal carriage of blakpc producing carbapenem-resistant Enterobacteriaceae: who is prone to become clinically infected? Clin Microbiol Infect 2013;19: Inns T, Millership S, Teare L, Rice W, Reacher M. Service evaluation of selected risk factors for extended-spectrum beta-lactamase Escherichia coli urinary tract infections: a case-control study. J Hosp Infect 2014;88: Wu YH, Chen PL, Hung YP, Ko WC. Risk factors and clinical impact of levofloxacin or cefazolin nonsusceptibility or ESBL production among uropathogens in adults with community-onset urinary tract infections. J Microbiol 29

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A 617 Special Issue Diabetic Retinopathy Won Ki Lee, M.D. Department of Ophthalmology The Catholic University of Korea College of Medicine Kangnam St. Mary s Hospital E mail : wklee@catholic.ac.kr Abstract R