Transcript ｽﾗｲﾄﾞ ﾀｲﾄﾙなし

9th International Catholic Urology Symposium
9th. June. 2007
Catholic Research Institute oｆ Medical Science, Seoul, Korea
Japanese guidelines for the treatment of
UTIs & STDs;
for making up KAUTI guidelines
Tetsuro Matsumoto, MD, PhD
Professor and Chairman, Department of Urology, University of Occupational
and Environmental Health, Kitakyushu, Japan
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I met him in 1998.
Our history started at that time!!
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Sister relationship between Department of Urology,
Catholic University and UOEH Dec. 2000, Seoul
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Sister relationship between Department of Urology,
Catholic University and UOEH
March, 2001, Kitakyushu
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Asian Association of UTI/STD (AAUS)
President; Tetsuro Matsumoto (Japan),
Vice president; Yong-Hyun Cho (Korea),
Organizing Committee; Paul A. Tambyah
(Singapore), Min Eui Kim (Korea), Hiromi
Kumon
(Japan),
Prasit
Tharabichitkul
(Thailand), Bill Wong (Hong Kong), Xiang Shen
Chen (China), Yodor Lim (Philippines),,Iwan
Asmara Achmad (Indonesia), Stephen Yang
(Taiwan), Roman Kozlof (Russia), Chul Sung
Kim (Korea)
Secretary; Tetsuro Muratani (Japan), Sang Don
Lee (Korea), Vladimir Rafalski (Russia)
International Advisory Committee; Kurt Naber
(Germany), Jean Claude Pechere (Switzerland),
John Krieger (USA)
Honorary Members; Joichi Kumazawa (Japan),
Yoshiaki Kumamoto (Japan), Sadao Kamidono
(Japan), Chong Wook Lee (Korea), Nicolay
Lapatkin (Russia)
Established in 2003
3rd Board Meeting in Seoul
15, May, 2005
(Photo by K. Naber)
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Guidelines for the treatment of
urinary tract infection (UTI)
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IDSA Guidelines for the treatment of UTIs
Clin. Infect. Dis. 29:745-758,1999.
Excellent evidence-based guidelines, however…….
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Guidelines for the treatment of UTIs
Eur. Urol. 40:576-588,2001.
Made by Urologists, however…..
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Need our own guidelines?
These guidelines are quite excellent and helpful for
us.
However, our own guidelines are necessary, because
there are many difference in the region or areas in
many points of view such as antimicrobial
susceptibility pattern, patients characteristics, drug
use tendency, government’s policies, insurance
systems etc.
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Japanese guidelines for antimicrobial use
Japanese Society of Infectious
Diseases & Japanese Society of
Chemotherapy, 2005
Part of UTI and STD were described
by urologists, and guidelines were tried
fit to other guidelines which were made
by the other societies.
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Uncomplicated UTI
Acute uncomplicated cystitis
Acute uncomplicated pyelonephritis
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Isolation frequency of bacteria
in urinary tract infection
Uncomplicated UTI
S. epidermidis
E. faecalis
Complicated UTI
Citrobacter &
CNS Enterobacter
Klebsiella
spp.
E.coli
GPC Fungi Citrobacter &
Enterobacter
Streptococci
E.coli
CNS
S. epidermidis
MSSA
Klebsiella
spp.
MRSA
Proteus
Enterococcus
spp.
spp.
Serratia
marcescens
E. faecalis
P. aeruginosa
NFGNR
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Acute uncomplicated cystitis in women
A, I
A,II
B, I
E, I
ST 3d, OFLX 3d
NFLX 3d, CPFX 3d, FLRX 3d, Trimeth 3d
Nitrofran 7d, FOM SDT
b-lactam 3d
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Antibiotics selection for AUC in Japan
・Penicillins; Resistant bacteria(>30% in E. coli)
・Penicillin + BLI; Resistance rate in arround 14%
・Cephems; Immediate recurrence after 3 days regimen
・New oral cephems; Resistance rate in 2 to 13%. Duration of
treatment remains unknown.
・Fluoroquinolones; Good for 3 days regimen (resistance rate
in around 10%)
・Sulfo/Trim; Standard drug for AUC in US and
Europe, not in Japan
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Resistance rate in isolates from uncomplicated UTI
20
15
10
CPDX
CFDN
CDTR
CFPN
CPFX
LVFX
FOM
ST
NIT
0
CCL
CXM
CTM
CFTM
5
AMP
/SBT
AMOX
/CVA
FRPM
Resistant ratio (%)
25
E. coli 87、P. mirabilis 3, M. morganii, S. marcescens, K.
pneumoniae, Gram-positive bacteria 14
Ampicillin
/sulbactam
Amoxicillin
/clavulanate
Faropenem
Cefaclor
Cefuroxime
Cefotiam
Cefteram
Cefpodoxime
Cefditoren
Cefcapene
Ciprofloxacin
Levofloxacin
Fosfomycin
Co-trimoxazole
Nitrofurantoin
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Initial treatment of acute uncomplicated cystitis
Drugs
Treatment duration
Oral
Fluoroquinolones
New oral cephalosporins
Penicillins + BLI
3 days
7 days
7 days
Pregnant women
Elderly women
New oral cephalosporins
Fluroquinolones
3 days
3 to 7 days
（Japanese guideline,2005）
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Acute uncomplicated pyelonephritis in women
A, I
A,II
14d therapy
mild case：oral NQ,
severe case：parenteral NQ
B, I
mild or moderate case-7d therapy
B,II
mild case-ST
B,III GPC-AMPC, AMPC/CVA
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Initial treatment of acute uncomplicated pyelonephritis
Drugs
Treatment duration
Oral
Fluoroquinolones
New oral cephalosporins
7 to 14 days
14 days
Parenteral
1st to2nd gen. cephalosporins
Penicillins + BLI
+ Aminoglucosides
Parenteral fluoroquinolones
Switch to oral fluoroquinolones 14 days
or cephalosporins
（Japanese guideline,2005）
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Complicated UTI
Chronic complicated cystitis
Chronic complicated pyelonephritis
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Complicated UTI
・Predisposing factors in the urinary tract or whole body
・Should be controlled predisposing factors
・Should not be treated only by antimicrobials
・Various causative bacteria
・Antimicrobial-resistant bacteria
・Proper use of antimicrobials to prevent increase of
antimicrobial-resistant bacteria
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EAU guideline for complicated UTI
1.UTI with complicating factors or Nosocomial UTI
Initial therapy; NQ, Penicillins/BLI, II~III Cephems,
Aminoglycosiges
Duration of therapy;3-5 days after defevescence
or control/ elimination of complicating factors
2. In case of failure of initial therapy or severe case
NQ if not used initially, Penicillin/BLI, III Cephems,
Carbapenems + Aminoglycosides
3. In case of candida
Fluconazole, Amphotericin B
( Naber et al, Eur Urol,2001)
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Isolation frequency of bacteria
in urinary tract infection
Uncomplicated UTI
S. epidermidis
E. faecalis
Complicated UTI
Citrobacter &
CNS Enterobacter
Klebsiella
spp.
E.coli
GPC Fungi Citrobacter &
Enterobacter
Streptococci
E.coli
CNS
S. epidermidis
MSSA
Klebsiella
spp.
MRSA
Proteus
Enterococcus
spp.
spp.
Serratia
marcescens
E. faecalis
P. aeruginosa
NFGNR
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Enterococcus faecalis (n=192)
PCG
ABPC
PIPC
FRPM
CPR
CZOP
IPM
MEPM
GM
AMK
CPFX
LVFX
TFLX
GFLX
MINO
CAM
TEL
Range
1-16
1-8
2-32
0.5-16
0.5->128
8->128
0.5-8
2-64
4->512
32-256
0.25-128
0.5-128
0.125->32
0.125-32
0.06-32
0.06->128
0.16-8
BP
8
8
16
2
8
8
4
4
512*
16
1
2
2
2
4
2
2
S-ratio
97.4
100
99.0
73.4
7.6
0.6
98.4
10.3
73.4
0
55.1
63.0
67.6
68.8
27.6
35.9
92.2
Range
ST
0.016->16
VCM
0.125-32
TEIC
0.06-16
LZD
0.125-4
QPR/DPR 0.03->16
ABK
8->128
BP
2
4
8
2
1
4
S-ratio
85.4
100
100
99.0
1.1
0
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Escherichia coli (n=283)
ABPC
PIPC
CEZ
CTM
CAZ
CTRX
CTX
CPR
AZT*
IPM
MEPM
CMZ
CCL
CPDX
Range
0.25->128
0.125->128
0.5->128
0.03-128
0.06-16
0.004->128
0.008->128
0.016-64
0.008-16
0.06-2
0.004-0.125
0.25-128
0.25->128
0.06->128
BP
8
16
8
8
8
8
8
8
8
4
4
16
8
2
S-ratio
61.1
84.8
92.6
96.8
98.6
97.2
97.9
98.2
97.6
100
100
99.7
90.5
90.1
CPFX
LVFX
GFLX
MINO
AMK
ISP*
Range
0.008-128
0.008->128
0.008-128
0.25-128
0.5->128
0.5->128
BP
1
2
2
4
16
16
S-ratio
80.2
79.2
80.2
87.6
99.7
99.5
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Pseudomonas aeruginosa (n=242)
Range
PIPC
0.25->256
PIP/TAZ 0.25->256
CPZ
0.5->128
CPZ/SBT 0.5->128
CAZ
0.5->256
CFS
0.5->128
CPR
1->128
CZOP 0.5->128
AZT
1->128
IPM
0.25-128
MEPM 0.03->128
BP*
64
64
16
16
8
8
8
8
8
4
4
S-ratio**
87.2
93.0
73.1
74.4
78.9
70.7
66.9
77.3
67.4
74.4
78.5
GM
AMK
ISP
TOB
CPFX
LVFX
TFLX
PZFX
PUFX
MINO
ST
PL-B
Range
0.25->128
1->128
1->128
0.25->125
0.03->128
0.125->128
0.03->32
0.03-64
0.06->128
4->128
0.25->16
0.5-16
BP
S-ratio
4
85.5
16
92.6
16
91.7
4
88.0
1
76.9
2
70.7
1
77.3
4
80.6
1
78.5
4
3.7
2
4.6
MIC90 = 4
*Breakpoint MIC, **Susceptible ratio
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Treatment drugs for the complicated cystitis
（Oral）
Fluoroquinolones
Cephalosporins
Penicillins + BLI
Duration; 7 to 14 days
（Japanese guideline, 2005）
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Treatment of complicated pyelonephritis
1. Select drugs among
2nd to 3rd gen chapalosporins, penicillins + BLI,
Aminoglycosides and carbapenems
according to patient’s characteristics and
suspected pathogens
2. Switch to oral drugs 3 to 5 days after
defevescence in patients with high fever (38C)
Duration of treatment; 2 weeks,
3 to 4 weeks for
opportunistic pathogens
(Japanese guideline, 2005)
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Treatment guidelines for STDs
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Guidelines for the treatment of STDs
Sexually Transmitted Diseases Treatment Guidelines, 2006;
Workowski KA, Berman SM, MMWR 55(RR11):1-94,2006.
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Japanese guidelines for STDs
Guidelines for the diagnosis and treatment of STDs 2006;
Japanese Society for Sexually Transmitted Diseases
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Genital Chlamydial infection
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Genital chlamydial infection
48-72hr
0hr
EB
Host cell
6-8hr
RB
20-24hr
inclusion
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Azithromycin 1g orally single dose
Doxycycline 100mg orally twice a day 7days
Erythromycin base 500mg four times a day 7 days
Erythromycin ethylsuccinate 800mg orally four times a day 7 days
Ofloxacin 300mg orally twice a day 7days
Levofloxacin 500mg orally once a day 7 days
UOEH urology
Trends of genital Chlamydial infection in Japan
• Genital chlamydial infection is the most common STDs in both sex.
• Half of male urethritis was caused by C. trachomatis.
• Both of gonococcus and chlamydia were detected concomitantly in 2030% male urethritis.
• C. trachomatis was concomitantly detected in the pharynx in 10-20% of
female genital chlamydial infection.
• Asymptomatic chlamydial infection has been increasing in high school
students, especially in girls.
• PCR is the most popular detection methods.
• Newer detection kits such as BD probe-Tech and
Aptima-Combo 2 are now available.
• While PCR negative mutant strains were detected in high rate
in Sweden and other European countries, no such strains was
identified in Japan.
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Japanese guideline for the treatment of
genital chlamydial infection （2006）
Oral drug
1）Azithromycin
1,000mg x 1
Single dose
2) Clarithromycin
200mg x 2
7 days
3）Minocycline
100mg x 2
7 days
4）Doxycycline
100mg x 2
7 days
5）Levofloxacin
100mg x 3
7 days
6）Tosufloxacin
150mg x 2
7 days
7) Gatifloxacin
200mg x 2
7 days
3）〜7）;should not use for pregnant women
Parenteral drug (Severe case)
Minocycline 100mg x 2 div 3〜5 days followed by oral drug
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Gonococcal infection
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Uncomplicated gonococcal infections of the cervix, Urethra, and Rectum
Ceftriaxone 125mg IM single dose
Cefixime 400mg orally single dose
Ciprofloxacin 500mg orally single dose
Ofloxacin 400mg orally single dose
Levofloxacin 259mg orally single dose
+ Treatment for Chlamydia if not ruled out
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Trends of gonococcal infection in Japan
• Gonococcus has been changing in infecting sites, and the pharynx has
been the most important infection site.
• PCR is not suitable detection method for the pharyngeal infection.
• Susceptibility of N. gonorrhoeae to antimicrobial such as
fluoroquinolones, penicillins, tetracyclines, macrolides and oral
cephalosporins has been quite low. Therefore, no oral drugs were not
able to use in the treatment.
• Parenteral drugs such as ceftriaxone, cefodizime and
spectinomycin are effective for the treatment of gonococcal
urethritis and cervicitis.
• Ceftriaxone is the most suitable drug for the treatment of
gonococcal infections including pharyngitis.
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Prevalence of drug resistant strain of
N. gonorrhoeae in 5 areas (2005)
Resistant ratio (%)
100
80
60
40
（STD reseach
group in
Kitakyushu &
KAUTI)
20
0
Oral A
cephems
B
Quinolones
C
D
Penicillin
Tetracycline
■: Kitakyushu (n=238), ■: Yamaguchi (n=80),
■: Tokyo (n=88), ■: Nagoya (n=93), ■: Korea UOEH
(n=29)urology
Japanese guideline for the treatment of
gonococcal infection （2006）
Ceftriaxone 1.0g Single dose;
Urethritis, Cervicitis, Pharyngitis etc
Cefodizime 1.0g
Single dose;
Urethritis & Cervicitis
Multiple doses are necessary for pharyngitis
Spectinomycin 2.0g Single dose;
Urethritis & Cervicitis単回投与
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Summary
1. We need our own guidelines based on the our own
evidences and the local antimicrobial susceptibility.
2. It also should match to insurance system.
3. It should be revised every 2 or 3 years.
Thank you very much
for your attention
Manneken pis in my home
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