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1 대한요로생식기감염학회지 : 제3권제2호 2008년 10월 Korean J UTII Vol.3, No.2, October 2008 종설 노령에서의요로감염과세균뇨 : 진단과치료 대구가톨릭대학교의과대학비뇨기과학교실김덕윤 [Abstract] Urinary Tract Infections and Bacteriuria in the Elderly: Diagnosis and Treatment Duk Yoon Kim From the Department of Urology, College of Medicine, Catholic University of Daegu, Daegu, Korea The elderly population is now increasing in the world. A higher incidence of bacteriuria and urinary tract infection (UTI) is observed in the elderly patients, in both long-term care facilities and at home. The management of elderly patients with UTI is increasing in clinical significance. Bacteriuria ( 10 5 CFU/ml) is a very common phenomenon in the elderly people, occurring twice as frequently in women than in men. Almost all of UTI in the elderly is complicated UTI. Control of the underlying diseases in the urinary tract is quite important in the management of UTIs in the elderly patients. For pyelonephritis, switch therapy using aminoglycosides and fluoroquinolones, carbapenems, third-generation cephalosporines, or penicillins are selections of choice. The recommended duration of treatment for patients with pyelonephritis is 14 days. Seven to 10 days of treatment using fluoroquinolones or trimethoprim-sulfamethoxazole is recommended for the treatment of elderly patients with symptomatic cystitis. There are symptomatic and asymptomatic types of bacteriuria. Although asymptomatic bacteriuria is quite common in the elderly population, antibiotic treatment has no benefit for such patients. Intravaginal estrogen replacement is one of choice for the prevention of recurrent UTIs in postmenopausal women. (Korean J UTII 2008;3: ) Key Words: Urinary tract infection, Elderly 서 노인인구의전세계적급증으로요로감염역시증가추세에있으며, 폐렴, 피부감염다음으로노인들 론 교신저자 : 김덕윤, 대구가톨릭대학교의과대학비뇨기과학교실대구광역시남구대명 4 동 Tel: , Fax: dykim@cu.ac.kr 160 에게가장흔한세균감염인요로감염으로급성고열이나패혈증에빠지는주원인이되기도한다. 노인에있어임상증상은다양하여무증상으로지낼수있고혹은심한경우패혈증으로나타나기도한다. 1 그러나대부분의환자에서는증상이없거나가벼운증상으로외래진료를통하여진단및치료가이루어지지만요양기관에있거나면역기능이약화된환자에서는패혈증으로진행하여사망에이르기도

2 김덕윤 : 노령에서의요로감염과세균뇨 : 진단과치료 161 쉬운질환이다. 저자는노인의요로감염과무증상세균뇨를중심으로진단과치료에있어서특징및차이점을알아보고자한다. 본론 1. 진단 1) 요로감염의진단일반주거지의노인은젊은연령에서와같은수의세균 ( 10 5 CFU/ml) 이요로생식기증상과함께동반되었을때로진단하나인지력이정상이지않은노인에서는무증상세균뇨와요로감염을구분하기쉽지않다. 검사실소견으로유의한세균뇨 ( 10 5 CFU/ml), 농뇨 (>10 백혈구 /HPF) 는최소한의기준이나충분한기준은아니다. 증상을동반한요로감염은요로생식기의증강을동반한유의한세균뇨로정의할수있다. 도뇨관을착용하지않은요양시설환자는 100.4F 이상의고열, 배뇨통, 빈뇨, 요절박이심해지거나새로나타나는경우, 측복부동통, 치골상부동통이새로생기거나, 뇨의성상이변하는경우, 의식이나신체기능이악화되는다섯가지중세가지이상에해당되는경우로정의한다. 장기간도뇨관을착용하는환자는 100.4F 이상의고열, 측복부동통, 치골상부동통이새로생기거나, 뇨의성상이변하는경우, 의식이나신체기능이악화되는네가지중두가지이상에해당되는경우로정의한다. 2 이기준은 The Association for Professionals in Infection Control 및 The Society for Healthcare Epidemiology of America라는두개의미국내국가감염관리기구의기준으로채택된것이다 전립선염과요로감염 2) 무증상세균뇨의진단요로감염에연관된증상이나증후가없는오염되지않은요배양검사를기준으로진단한다. 여성의무증상세균뇨는 2회연속배뇨한뇨에서 10 5 CFU/ ml 이상의균이나온경우이고, 무증상남성은일회의청결하게채취된뇨에서 10 5 CFU/ml 이상이, 남녀 공히일회도뇨한뇨에서 10 5 CFU/ml 이상인경우일때진단한다 원인균 1) 요로감염을일으키는원인균요로감염과관련된패혈증의 80% 는 gram-negative organisms ( 대부분 Escherichia coli, E. coli) 이고 20% 는 gram-positive organisms ( 예, Enterococcus 또는 methicillin-resistant Staphylococcus aureus) 이다. 5 요양시설의경우 E. coli가가장흔하나기회감염균인 Pseudomonas. aeruginosa, vancomycin-resistant enterococci, Candida spp, non-e. coli Enterobacteriaceae도흔히동정된다. 6 2) 무증상세균뇨의원인균주로상행성감염에의하며소화기, 질, 요도주위에서기인한다. E. coli는여성과남성의무증상세균뇨의 75~80% 에서분리되는가장흔한균이며, 7,8 다른균은 Enterobacteriaceae ( 예, Klebsiella pneumoniae, coagulase-negative staphylococci, Enterococcus species, group B streptococci, Gardnerella vaginalis) 등이다. 2 일반주거지의노인에서는 E. coli, coagulase-negative staphylococci가가장흔한분리균주이다. Proteus mirabilis, Providencia stuarti, K. pneumoniae는요양시설에서흔히분리되며장기간도뇨관유치환자는 Pseudomonas. mirabilis, P. stuarti, P. aeruginosa 등이 biofilm에서흔히분리된다 치료 1) 요로감염의치료폐혈증이의심되는급성환자는 3세대 cephalosporin 단독으로경험치료를배양균의감수성검사결과가나올때까지적용한다. 폐렴이나피부궤양등그람양성감염이의심되는경우가아니면 vancomycin 은사용하지않는다. 5 한편외래에서의치료는 fluoroquinolones이일차치료제로사용된다. 도뇨관이없는일반주거지의노인에서항균제시작의최소기준은배뇨통이나 37.9 이상고열, 기초체온에서

3 162 대한요로생식기감염학회지 : 제 3 권제 2 호 2008 년 10 월 Table 1. Antimicrobial agent, dose, dosing interval, and duration for the treatment of uncomplicated cystitis in women Drug and dose Dosing interval Duration Comments Amoxicillin, 250 or 500mg q8 hours (250mg) to q12 hours (500mg) 7 days Useful in pregnancy and for enterococcal UTI Amoxicillin-clavulanate, 250/125mg or 500/125mg q8 hours (250/125mg) to q12 hours (500/125mg) 7 days Alternative with TMP-SMZ and fluoroquinolone resistance Cefixime, 400mg q24 hours 7 days Not available in the United States currently Ciprofloxacin, 250mg q12 hours 3 days Use sparingly (avoid resistance) Ciprofloxacin, 500mg, q24 hours 3 days Use sparingly (avoid resistance) extended release Fosfomycin, 3g Single dose NA Third line, resistance uncommon Levofloxacin, 250mg q24 hours 3 days Use sparingly (avoid resistance) Nitrofurantoin monohydrate or macrocrystals, 100mg q12 hours 5~7 days Alternative if TMP-SMZ allergy, or local TMP-SMZ resistance prevalence is greater than 20% Trimethoprim, 100mg q12 hours 3 days For patients with sulfa allergy TMP-SMX, 160/800mg q12 hours 3 days Preferred if local TMP-SMZ resistance prevalence is less than 20% Abbreviations: q, every; TMP-SMX, trimethoprim-sulfamethoxazole. 1.5 이상체온상승혹은요절박, 빈뇨, 치골상부동통, 육안적혈뇨, 측복부동통, 요실금이새로생기거나악화된경우이다. 도뇨관이있는경우는 37.9 이상고열, 기초체온에서 1.5 이상체온상승혹은치골상부동통, 오한, 섬망등이다. 증상을동반한합병증이없는여성환자에서는대장균이가장흔한균이므로 3~7일혹은 7~10일간의 trimethoprim-sulfamethoxazole 혹은 fluoroquinolones으로치료할수있다. 표 1은합병증이없는여성환자의방광염치료에서항균제선택, 치료기간, 용량등에관한내용을요약한것이다. 증상을동반한상부요로감염은요배양검사가필요하여동시감염이나내성균을진단할수있다. 경험적치료는기존의자료를근거로시작하며최소 10일간은지속한다. 신우신염치료로는 aminoglycosides 와 fluoroquinolones, carbapenems, 3세대 cephalosporines 혹은 penicillins을이용한 switch therapy를선택한다. 치료기간은 14일을기준으로한다. 표 2는합병증을동반하지않은여성상부요로감염의항균제선택, 용량, 기간, 방법을요약한것이다. 2) 무증상세균뇨의치료노인의무증상세균뇨는제한적으로치료하도록권장되고있다. The Infectious Diseases Society of America에서는당뇨병을가진여성, 요양시설혹은일반거주노인, 척수손상환자, 도뇨관유치환자에는치료를하지않도록권고하고있다. 4 3일간항균제요법이 6개월후세균뇨의빈도를줄이지만이환율, 사망률, 요실금의발생에는큰이익이없다. 9 표 3은무증상세균뇨를대상으로무작위연구결과를요약한것이다. 노인의무증상세균뇨는경요도전립선절제술과점막출혈이예상되는비뇨기과수술전외에는치료가권고되지않는다. 요로계이외의증상이항균제사용의중요인자이지만근거이유는불충분하다 예방 1) 요로감염의예방요로감염을예방하기위해 cranberry tablet이나 juice 를투여하나충분한효과가있는지는입증되지않았다. 폐경후질내 etrogen 적용은재발성요로감염을줄이는것으로보인다. 장기간예방적항균제의

4 김덕윤 : 노령에서의요로감염과세균뇨 : 진단과치료 163 Table 2. Antimicrobial agent, dose, dosing interval, route of administration, and duration for the treatment of uncomplicated pyelonephritis in women Drug and dose Comments Dosing interval Route of administration Duration of therapy Amoxicillin, 875mg q12 hours Oral 10~14 days Useful in pregnancy and for enterococcal UTI; many E coli are resistant Amoxicillin-clavulanate, 875/125mg q12 hours Oral 10~14 days Useful in pregnancy and for enterococcal UTI; many E coli are resistant Ampicillin, 1g [a] q6 hours Intravenous Variable [b] Combined with gentamicin for enterococcal activity Ampicillin-sulbactam, q6~q8 hours Intravenous Variable [b] Many E coli are resistant 1.5~3g Aztreonam, 1g q8~q12 hours Intravenous Variable [b] Alternative for penicillin or cephalosporin allergy Cefepime, 1g q8~q12 hours Intravenous Variable [b] Anti-Pseudomonas activity Ceftriaxone, 1g q24 hours Intravenous Variable [b] Initial therapy Ciprofloxacin, 400mg q12 hours Intravenous Variable [b] Initial therapy Ciprofloxacin, 500mg q12 hours Oral 7 days Initial or continuation therapy Gentamicin, q24 hours Intravenous Variable [b] Initial therapy (often combined with ampicillin) 3~5mg/kg [c] Imipenem, 500mg q8 hours Intravenous Variable [b] Initial therapy (for complicated or severe disease) Levofloxacin, 250 or 750mg Piperacillin-tazobactam, 3.375g TMP-SMX, 160/800mg Abbreviation: q, every. [a] [b] [c] q24 hours Intravenous or oral 7~10 days (250mg), 5 days (750mg) Initial or continuation therapy q6 hours Intravenous Variable [b] Initial therapy (complicated or severe infection) q8~q12 hours Intravenous/oral 10~14 days Initial/continuation therapy; many E coli are resistant Combined with gentamicin if used for empiric therapy. It is expected that most patients can be transitioned from an intravenous regimen to an oral regimen. Can be combined with ampicillin if the suspicion for enterococci is high. Table 3. Prospective randomized studies of treatment of asymptomatic bacteriuria Author Subjects Intervention Outcome Nicolle, et al 10 Nicolle, et al 11 Abrutyn, et al 12 Ouslander, et al 13 Men, nursing home residents; median age 80 years Women, nursing home residents; median age 83 years Women, ambulatory apartment and nursing home residents; mean age 82 years Women and men, nursing home residents; mean age 85 years Treated: 16 Not treated: 20 Duration of study: 2 years Treated: 26 Not treated: 24 Duration of study: 1 year Treated: 192 Not treated: 166 Duration of study: 8 years Treated: 33 Not treated: 38 Duration of study: 4 weeks No differences in mortality or infectious morbidity between the two groups. No differences in mortality and genitourinary morbidity between the two groups. Increased adverse drug reactions and antimicrobial resistance in the treatment group No survival benefit from antimicrobial therapy in the treatment group compared with the control group. No differences in chronic urinary incontinence between the two groups.

5 164 대한요로생식기감염학회지 : 제 3 권제 2 호 2008 년 10 월 Table 4. Underlying conditions that define a urinary tract infection as complicated Category Specific condition Anatomic/functional Solitary kidney Polycystic kidney (s) Instrumentation Indwelling or intermittent catheter Ureteral stent Percutaneous nephrostomy tube Vesicoureteral reflux Surgical reconstruction Ileal diversion Bladder augmentation Renal transplant Duplicated collecting system Obstruction Enlarged prostate Calculi Neurogenic bladder Ureteral obstruction other than calculi Tumor Fibrosis Stricture Medical Diabetes mellitus Chronic renal failure 사용은 6개월내에증상을동반한요로감염이나 12 개월내 3회이상의감염에효과적이다. 6개월간야간에 1회의항균제복용이추천되며 2년간계속복용한경우도있다. 약제는 trimethoprim-sulfamethoxazole, nitrofurantoin, cefalexin 등이다. 재발성요로감염의위험인자는요실금, 방광류, 잔뇨, 도뇨관사용, 항균제사용, 신체이상, 치매, 변실금, 콘돔카테터사용등이다 노인의요로감염은표 4와같은원인질환에합병하여발생하는경우가많으므로이를우선고려하여원인을제거하는것이중요하다. 합병증을동반한요로감염이란단순요로감염이아닌원인질환을가진경우로설명할수있으며일반적으로노인의요로감염은합병증을동반한경우로간주하지만이에대한근거는부족하다. 2) 무증상세균뇨의예방 cranberry juice가노인의무증상세균뇨를줄인다는연구보고가있으나전적으로권장되지는않는다. 18,19 폐경후여성을위한질내 estriol 치료는대조군에비해무증상세균뇨의발생을줄인다고보고하였으나모든경우에적용되지는않는다. 장기간의도뇨관유치는피하는것이좋고콘돔카테터가오히려부작용이적으면서환자에게불편감을줄이는장점이있다. 20 REFERENCES 1. Beyer I, Mergam A, Benoit F, Theunissen C, Pepersack T. Management of urinary tract infections in the elderly. Z Gerontol Geriatr 2001;34: McGeer A, Campbell B, Emori TG, Hierholzer WJ, Jackson MM, Nicolle LE, et al. Definitions of I-fe-tion for surveillance in long term care facilities. Am J Infect Control 1991;19: Smith PW, Rusnak PG. Infection prevention and control in the long-term-care facility. SHEA Long-Term-Care Committee and APIC Guidelines Committee. Infect Control Hosp Epidemiol 1997;18: Nicolle LE, Bradley S, Colgan R, Rice JC, Schaeffer A, Hooton TM, el al. Infectious diseases society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis 2005; 40: Ackermann RJ, Monroe PW. Bacteremic urinary tract infection in older people. J Am Geriatr Soc 1996;44: Nicolle LE. Resistant pathogens in urinary tract infections. J Am Geriatr Soc 2002;50:S Boscia JA, Kobasa WD, Knight RA, Abrutyn E, Levison ME, Kaye D. Epidemiology of bacteriuria in an elderly ambulatory population. Am J Med 1986;80: Monane M, Gurwitz JH, Lipsitz LA, Glynn RJ, Choodnovskiy I, Avorn J. Epidemiologic and diagnostic aspects of bacteriuria:a longitudinal study in older women. J Am Geriatr Soc 1995;43: Boscia JA, Kobasa WD, Knight RA, Abrutyn E,

6 김덕윤 : 노령에서의요로감염과세균뇨 : 진단과치료 165 Levison ME, Kaye D. Therapy vs no therapy for bacteriuria in elderly ambulatory nonhospitalized women. JAMA 1987;257: Nicolle LE, Bjornson J, Harding GK, MacDonell JA. Bacteriuria in elderly institutionalized men. N Engl J Med 1983;309: Nicolle LE, Mayhew WJ, Bryan L. Prospective randomized comparison of therapy and no therapy for asymptomatic bacteriuria in institutionalized elderly women. Am J Med 1987;83: Abrutyn E, Mossey J, Berlin JA, Boscia J, Levison M, Pitsakis P, et al. Does asymptomatic bacteriuria predict mortality and does antimicrobial treatment reduce mortality in elderly ambulatory women? Ann Intern Med 1994;120: Ouslander JG, Schapira M, Schnelle JF, Uman G, Fingold S, Tuico E, et al. Does eradicating bacteriuria affect the severity of chronic urinary incontinence in nursing home residents? Ann Intern Med 1995;122: Walker S, McGeer A, Simor AE, Armstrong-Evans M, Loeb M. Why are antibiotics prescribed for asymptomatic bacteriuria in institutionalized elderly people? Aqualitative study of physicians and nurses perceptions. CMAJ 2000;163: Stamm WE, Raz R. Factors contributing to susceptibility of postmenopausal women to recurrent urinary tract infections. Clin Infect Dis 1999;28: Nicolle LE, Henderson E, Bjornson J, McIntyre M, Harding GK, MacDonell JA. The association of bacteriuria with resident characteristics and survival in elderly institutionalized men. Ann Intern Med 1987;106: Ouslander JG, Greengold B, Chen S. External catheter use and urinary tract infections among incontinent male nursing home patients. J Am Geriatr Soc 1987;35: Avorn J, Monane M, Gurwitz JH, Glynn RJ, Choodnovskiy I, Lipsitz LA. Reduction of bacteriuria and pyuria after ingestion of cranberry juice. JAMA 1994;271: Raz R, Stamm WE. A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections. N Engl J Med 1993;329: Saint S, Kaufman SR, Rogers MA, Baker PD, Ossenkop K, Lipsky BA. Condom versus indwelling urinary catheters: a randomized trial. J Am Geriatr Soc 2006; 54:

- 위성헌. 요로감염의진단과치료 - 염과상부요로감염을감별하는데중요한요소로간주하고있는데, 적절한항생제치료에도불구하고 48-72시간이상발열이지속되는상부요로감염환자에서는신농양등다른합병증의발생가능성을고려해야한다. 남자의전립선염은배뇨통, 빈뇨, 긴박뇨등의방광염증상이나가는소변줄,

- 위성헌. 요로감염의진단과치료 - 염과상부요로감염을감별하는데중요한요소로간주하고있는데, 적절한항생제치료에도불구하고 48-72시간이상발열이지속되는상부요로감염환자에서는신농양등다른합병증의발생가능성을고려해야한다. 남자의전립선염은배뇨통, 빈뇨, 긴박뇨등의방광염증상이나가는소변줄, 개원의연수강좌 요로감염의진단과치료 가톨릭대학교의과대학내과학교실 위성헌 서론요로감염은방광, 신장, 요도, 전립선등요로계의세균감염을의미하고감염부위, 증상, 기저질환, 요로의해부학적혹은기능적이상에따라다양하게분류되며, 이러한분류에따라치료제의선택이나투여기간이달라질수있다. 즉, 감염부위에따라상부요로감염 ( 신우신염 ) 및하부요로감염 ( 방광염, 요도염, 전립선염, 부고환염