07 년 대한요로감염학회 춘계학술대회 the principles of antimicrobial therapy in...
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07 년 대한요로감염학회 춘계학술대회 The Principles of antimicrobial Therapy in Urinary Tract Infection. Wan-Shik Shin, MD Division of Infectious Diseases Department of Internal Medicine The Catholic University of Korea, Seoul, Korea. 나이와 성별에 따른 역학적 특성. bacterial attributes. host factors. - PowerPoint PPT PresentationTRANSCRIPT
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07 년 대한요로감염학회 춘계학술대회
The Principles of antimicrobial The Principles of antimicrobial Therapy in Urinary Tract InfectionTherapy in Urinary Tract Infection
Wan-Shik Shin, MD
Division of Infectious Diseases
Department of Internal Medicine
The Catholic University of Korea, Seoul, Korea
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나이와 성별에 따른 역학적 특성 age(yr)
females males
prevalence risk factors prevalence risk factors
<1 1 % anatomic or functional urologic abnormalities
1 % anatomic or functional urologic abnormalities
1-5 4-5 % congenital abnormalities, vesicoureteral reflex
0.5 % congenital abnormalities, uncircumcised penis
6-15 4-5 % vesicoureteral reflex 0.5 % none
16-35 20 % sexual intercourse, spermicide use, diaphragm use
0.5 % homosexuality, uncircumcised, HIV infection
36-65 35 % gynecologic surgery, bladder prolapse, postmenopausal estrogen deficiency
20 % prostatic hypertrophy, obstruction,surgery,catheterization
>65 40 % as for those age 36-65, plus incontinence, chronic catheterization
35 % as for those age 36-65, plus incontinence, long-term catheterization
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capsular antigens
hemolysins
urease
renal calculi
ureteric reflux
adhesion to uroepithelium (e.g. P fimbriae in E. coli)
Introital colonization
catheterizationshort urethra in women
prostatic hypertrophy
neurologic problems: incomplete bladder emptying large volume of residual urine loss of sphincter control
tumors in & adjacent to urinary tractpregnancy, bladder stones
Bacterial attributes and host factors favoring UTI
bacterial attributes host factors
catheterization
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요로감염 type 에 따른 원인균
Am J Med 1987;82(S4):278
Microbeacute
uncomplicated cystitis (%)
acute uncomplicated pyelonep
hritis (%)
complicated UTI (%)
catheter-associated
UTI (%)
E. coliS. saprophyticusProteusKlebsiellaEnterococciPseudomonasMixedOtherYeastS. epidermidis
791123203000
89044005200
32145
22201051
15
2406879
1110288
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807
3
64
%
outpatients
E.coli
Coagulase-negative staphylococci
Other Gram (+) e.g. S. epidermidis, S. aureus, E. faecalis
Hospital inpatients
40
25
115
16
3
%
Candida
Proteus mirabilis
Other Gram (-) e.g. Klebsiella, enterobacter, Serratia, P. aeruginosa
Common causes of UTI
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Laboratory Diagnosis of UTI (I)
• Urinalysis with microscopy– The presence of RBC & WBC, although abnormal : not necessarily indicative of UTI– Gram stain : 1 organism/X1000 105 CFU/mL– Dipstick test : nitrite, leukocyte esterase activity
• Hematuria – infection of the urinary tract and elsewhere(e.g. endocarditis)– Renal trauma, calculi, urinary tract carcinomas– Clotting disorders, thrombocytopenia
• Pyuria: ≥10/HPF(X400)
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Midstream clean-catch urine collection
Urine collection
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Urine collection (II)
Clean container without performing
any cleansing(n=77)
Midstream clean catch
technique(n=84)
Midstream clean catch technique and
used a vaginal tampon(n=81)
29% 32% 31%
Contaminated: mixed flora, <104 CFU/mL
Lifshitz E. Arch Intern Med 2000;160:2537-2540
Women with symptoms of cystitis (mean age : 21 years)
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정윤섭 , 진단미생물학 제 2 개정판 pp.95
Quantitative Culture of Urine
DDx : Infection or Contamination
0.001ml 백금이
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Significant bacteriuria
• 1950s, Kass : ≥ 105 CFU/mL in 2 consecutive midstream urine samples
• Revised definition– women with Sx of uncomplicated cystitis
• ≥ 103 CFU/mL + pyuria : sen. 80%, spe. 90% : IDSA• 실제 임상에서 균배양은 필요없음 ∵ 감수성이 비슷 , 결과가 늦음• Hx 만으로도 ≥ 90% 에서 충분 dysuria & frequency without vaginal discharge/irritation
– uncomplicated pyelonephritis & men with UTIs• ≥ 104 CFU/mL + pyuria
– complicated UTIs• ≥ 105 CFU/mL +/- pyuria• 주의 깊은 해석이 필요 : 검체의 종류 , 배양된 균종의 수• ≥ 2 균종 , ≤105 CFU/ml : contamination ?
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no prompt delivery or bad collection
probable infections but require confirmation
Significant bacteriuria
10 102 103 104 105 106 107
not infected infected
significant bacteriuria
No of bacteria/ml of urine
number of patients
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Asymptomatic bacteriuriaWhen to screen & when to treat ?
• Definition : bacteria in urine without clinical Sx & sign of UTI
microbiologic definition : ≥105 CFU/ml of organism(s)
in 2 consecutive urine specimens• Clinical importance ?
UTI complication : harmful ?, cross-protective effect : beneficial ?
• Recommendations for screening & Tx
beneficial : pregnant women, before traumatic GU procedure
may be beneficial : K/T recipient (≤6 mo),
women c persisent cath. acquired bacteriuria after cath. removal
not beneficial : healthy infants, girls, women/men, elderly men/women in community or long-term care facilities, pts c diabetes or HIV infection, pts with short-term or chronic indwelling urethral catheters, pts with intermittent catheterization, pts with neurologic impairment of bladder emptying, pts with chronic urologic device
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일반적 치료원칙 (I)
• 치료 시작 전 : 그람염색 , 소변배양 등을 통해 감염여부 확인 ( 예외 )
이후 배양검사에서 원인균이 밝혀지면 감수성있는 항생제 선택
• 지역사회획득 감염 , 특히 초감염 : 대부분 항생제에 감수성인 균주• 반복감염 , 요로 처치를 받은 사람 , 최근 병원 입원 : 내성균주 의심
• 선택 항생제 : 혈중농도보다 소변내 농도가 중요
• 치료기간 : 단순 하부요로 감염 ; 단기치료 , 상부감염 ; 더 장기간 치료
• 폐쇄와 결석과 같은 감염 선행인자의 교정
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일반적 치료원칙 (II)• 치료가 끝난 후 평가 : 증상 소실 ≠ 세균학적 완치 ≠ 치료 완료
- 실패 vs 완치 ?
- 재발 (recurrence)
재감염 (Reinfection) vs 재발 ? 조기 ( 치료 후 ≤ 2 주 ) vs 후기 재발 ?
• 조기 재발
상부요로의 감염이 완치되지 않아 재발 : 많지 않음
균주의 지속적 질내 정착에 인한 재감염 : 흔함 ( 특히 방광염 단기치료 후 )
• 후기 재발
대부분 새로운 균주에 의한 재감염
이전에 감염되어 질과 직장에 정착한 균주
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재발 (relapse)
• 신장침범 , 요로계의 구조적 이상이나 신석 , 만성 세균성 전립선염 등 host factor 여부를 확인
• 구조적 이상이 없는 재발의 치료 세균뇨가 없어질 때까지 치료 치료 중 세균뇨가 지속되거나 다시 세균뇨가 나타나면 항생제를 바꿈• 치료기간 단기 또는 7~10 일 치료한 경우 : 2 주간 치료 2 주 치료한 경우 : 4~6 주 치료 6 주 치료한 경우 : 6 개월 이상 치료• 치료 중 검사 매달 요배양 검사 , 장기치료를 받는 환자는 Ccr 측정과 1-2 년마다
IVP
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Factors in selecting antibiotics for the empiric Tx of uncomplicated UTI
• Antimicrobial spectrum• Pharmacokinetics : infrequent dosing intervals
• Local prevalence of resistance• Duration of adequate urinary levels (including renal tissue)
above the infecting organism’s MIC : important !
ex) shorter T ½ of ß-lactams : poor efficacy
• Effect of the antimicrobial on the fecal & vaginal flora
little effect on anaerobes : TMP-SMX, 1º & 2º fluoroquinolone• Potential for undesirable side effects• Cost of the treatment regimen• Public health concerns about resistance
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Antimicrobial Resistance : prevalance
• Significant increase in resistance among E. coli • TMP-SMX
U.S.A. : < 20%, Europe : < 35%, Korea : 40-50%• Fuoroquinolone
U.S.A. : < 2.5%, Europe : < 37%, Korea : 15-20%• Nitrofurantoin
excellent activity & low resistance against E. coli
but no activity against non-E. coli isolates : 10-30% in Korea• ß-lactams : no recommendation for 1st line empiric Tx
ampicillin : 26-38%, 60-70% in Korea
cephalothin : 28-39%, 20-30% in Korea
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Uncomplicated UTI Tx guidelines by IDSA (1999)Acute uncomplicated pyelonephritis
• Mild case
oral fluoroquinolone (A,II) or TMP-SMX (B,II) for 7d (B,I)
likely GPC : amoxicillin/clav. alone (B,III)
• Moderate to severe case : admission for parenteral Tx
fluoroquinolone (B,III) or
aminoglycoside ± ampicillin (B,III) or
extended spectrum cephalosporin ± aminoglycoside (B,III)
GPC : ampicillin-sulbactam ± aminoglycoside (B,III)
switch Tx to oral antimicrobial with improvement (B,III)
duration : moderate case : 7 d (B,I), severe case : 14 d (A,I)
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Uncomplicated UTI Tx guidelines by IDSA (1999)Acute uncomplicated pyelonephritis
• Mild case
oral fluoroquinolone (A,II) or TMP-SMX (B,II) for 7ds (B,I)
likely GPC : amoxicillin/clav. alone (B,III)
• Moderate to severe case : admission for parenteral Tx
fluoroquinolone (B,III) or
aminoglycoside ± ampicillin (B,III) or
extended spectrum cephalosporin ± aminoglycoside (B,III)
GPC : ampicillin-sulbactam ± aminoglycoside (B,III)
switch Tx to oral antimicrobial with improvement (B,III)
duration : moderate case : 7 ds (B,I), severe case : 14 ds(A,I)
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요로감염 치료를 위한 접근법
a. 요로감염 증상이나 요로계 폐쇄가 없는 임산부가 아닌 성인에서는 치료할 필요없음b. 모든 소아와 남자에서는 영상검사를 하여 의미있는 병변을 교정해야 함c. 임산부 , 소아 , 요로폐쇄가 있는 성인에서는 추적 배양검사가 필요함d. 임산부는 매달 , 소아는 6 주와 6 개월에 추적 배양검사가 필요함e. 만성 세균성 전립선염 유무 평가가 필요함f. 임산부에서는 분만 후 2 개월로 연기함g. 여성에서는 3 4∼ 회 재감염이 있을 경우 영상검사를 고려함
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세균성 요로감염의 치료임상진단 특징적인 병원체 고려할 사항 치료기간 및 선택항생제여성에서 발생한 단순 급성 방광염
E. coli, S. saprophyticus, P. mirabilis, K. pneumoniae
없음 3 일 요법 : 경구 TMP/SMX, TMP, quinolone
당뇨 , 7 일 이상의 증상 , 최근 요로감염 , 65 세 이상 , diaphragm 으로 피임
7 일 요법 : 경구 TMP/SMX, TMP, quinolone
임신 7 일 요법 : cefpodoxime proxetil, TMP/SMX, amoxicillin(/clavulanate)
여성에서 발생한 단순 급성 신우신장염
E. coli, P. mirabilis, S. saprophyticus
경증 또는 중등증 , 오심 /구토 없는 경우 ; 외래치료
경구 quinolone 7~14 일 ( 필요시 초기용량은 정주 ), ceftriaxone 또는 gentamicin 일회 정주 후 경구 TMP/SMX 14 일
중증 , 패혈증 우려 , 임산부 ; 입원치료
ceftriaxone, quinolone, gentamicin 또는 aztreonam 을 해열때까지 정주 후 경구 quinolone, cephalosporin 또는 TMP/SMX 14일
여성 , 남성에서 복잡 요로감염증
E. coli, Proteus, Klebsiella, Pseudomonas, Serratia, enterococci, staphylococci
경증 또는 중등증 , 오심 /구토 없는 경우 ; 외래치료
경구 quinolone 10~14 일
중증 , 패혈증 우려 ; 입원치료
ampicillin + gentamicin, quinolone, ceftriaxone, aztreonam, ticarcillin/clavulanate, imipenem-cilastatin 을 해열때까지 정주 후 경구 quinolone 또는 TMP/SMX 10~21 일
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THANK YOU !