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1 Clinical Practice Uncomplicated Urinary Tract Infection NEJM March15,2012 Thomas M. Hooton, M.D. H24.3 NEJM March15, 2012 Clinical Practice UTI UTI E.coli 2010 IDSA Infectious Diseases Society of America ecologic adverse effect collateral damage collateral damage underscore TMP80mg,SMX400mg g Nitrofurantoin Pivmecillinam E.coli 1/17

2 2 E.coli G 1 NEJM / / / / 1g/ / / / 5 TMP80mg, SMX400mg 2 2 / GM+AMPC UTI colonize UTI UTI /17

3 E.coli reservoir 28 1 UTI E.coli E.coli E.coli UPEC: Uropathogenic E.coli subset UPEC UPEC Klebsiella pnumoniae Staph.saprophyticus Enterococcus faecalis Str.agalactiae Enterococcus faecalis Streptococcus agalactiae UTI UTI 1 UTI D- mannose 3/17

4 D NEJM E.coli type1 pili FimH adhesin mannosylated receptor E.coli mannoside D-mannose adhesion blocker 38 CVA CVA esterase UTI UTI NEJM UTI UTI UTI UTI 7. 4/17

5 8. colonize UPEC 13. UPEC 14. UPEC 15. UTI UTI 1 sex 16. (+) CXCR1 IL8 17. UTI BMI. 18. E.coli Klebsiella pn Staph.saproph Enteroc.faec Str.agalac 20. Enterococcus faec Str.agalac CVA CVA 27. esterase UTI 75% 82% /ml IDSA 34. 2T2 / 3 3g GM+AMPC 5/17

6 T1 Uncomplicated Urinary Tract Infection NEJM March15,2012 H24.3 Thomas M. Hooton, M.D dysuria (urinary urgency) vaginal irritation (vaginal discharge) 1 trimethoprim-sulfamethoxazole 1 3 The Clinical Problem a / / 0.07 / / 6 25 acute uncomplicated pyelonephritis b. uncomplicated complicated 6/17

7 broad spectrum diversity, c. colonize Uropathogenic E.coli: UPEC subset fimbriae, flagella adhesin siderophores, polysaccharide coating 3 2 flora E.coli quiescent epithelial reservoirs biofilm d. spermicides sex partner 1 delayed voiding habits douching BMI 7/17

8 IL8 receptor CXCR1 P1 e. E.coli Klebsiella pneumoniae Staphylococcus saprophyticus Enterococcus faecalis Streptococcus agalactiae (Group B streptococcus) Enterococcus faecalis Streptococcus agalactiae 2. Strategies and Evidence a. 38 CVA CVA dipsticks esterase nitrites nitrate ( ) nitrite ( ) 8/17

9 esterase nitirites UTI UTI 10 5 /ml /ml no growth b , UPEC uropathogenic strains of E.coli amoxicillin 20 trimethoprim-sulfamethoxazole ( ) amoxicillin-clavulanate ( ) 10 nitrofurantoin fosfomycin mecillinam (pivmecillinam prodrug ) ESBL extended spectrum beta lactamase E.coli trimethoprim-sulfamethoxazole ( ) fosfomycin nitrofurantoin, amoxicillin-clavulanate vitro 9/17

10 IDSA Infectious Diseases Society of America adverse effects of antimicrobial agents collateral damage thresholds trimethoprim-sulfamethoxazole 20% 10 antibiogram c. first-line therapy) TMP-SMX TMP160mg-SMX800mg 2 / dose TMP80mg-SMX400mg TMP-SMX Fosfomycin trometamol 3g / 3g1 91 Nitrofurantoin 100mg 2 / Pivmecillinam / short-course regimens 5 ecologic adverse effects 10/17

11 NSAID Ciprofloxacin 250mg2 / / Levofloxacin 250mg/500 1 / d. 1 11/17

12 Ciprofloxacin / or 1g/ / 7 Ciprofloxacin: / / 7 96 Levofloxacin 750 / / 5 Levofloxacin / Levofloxacin 750 / / 5 86, Ciprofloxacin 500mg 2 / 81 Ciprofloxacin Levofloxacin TMP-SMX( ) / 14 TMP80mg,SMX E.coli E.coli 20 FDA IDSA TMP-SMX fluoroquinolones e. CT bacteremia 12/17

13 10 14 Ciprofloxacin / 200 /150ml 300 /150ml Levofloxacin / 500mg/20ml 500mg/100ml Ceftriaxone 1 2g 0.5g 1g Cefepime 1g 2 / 0.5g 1g Piperacillin-tazobactam 3.375g g 4.5g Meropenem 500mg g 0.5g Imipenam-cilastatin 500mg g, 0.5g Doripenem 500mg g 0.5g Ertapenem 1g1 1 Gentamycin 5-7 / g 6 f / 3 3g1 6 TMP-SMX( ) 1 QOL 13/17

14 g. diaphragm( ) Cranberry juice E.coli type1 pili FimH adhesin mannnosylated receptor E.coli mannoside D-mannnose adhesion blocker OTC TMP80mgSMX / / 3.6/ / Cephalexin( 250 )1 Nitrofurantoin TMP40mgSMX200mg ( ) 3 14/17

15 Cephalexin ( ) Fosfomycin 3g10 Nitrofurantoin h. CT dysuria (urinary urgency) vaginal irritation (vaginal discharge) 1 trimethoprim-sulfamethoxazole 1 3 TMP-SMX 3 Nitrofurantoin 5 phenazopyridine 3 / OTC 15/17

16 1. UTI UTI UTI UTI colonize UPEC 13. UPEC 14. UPEC 15. UTI UTI 1 sex 16. (+) CXCR1 IL8 17. UTI BMI. 18. E.coli Klebsiella pn Staph.saproph Enteroc.faec Str.agalac 20. Enterococcus faec Str.agalac CVA CVA 27. esterase UTI 75% 82% /ml 16/17

17 IDSA 34. 2T2 / 3 3g GM+AMPC T1 17/17

366 12 THE JAPANESE JOURNAL OF ANTIBIOTICS 65 6 Dec. 2012 1 8 DNA 2,3 16 12 20 171 2008 12 2010 11 2 3,558 4.44% 1.65% 1.17% 90% 9 Escherichia coli -

366 12 THE JAPANESE JOURNAL OF ANTIBIOTICS 65 6 Dec. 2012 1 8 DNA 2,3 16 12 20 171 2008 12 2010 11 2 3,558 4.44% 1.65% 1.17% 90% 9 Escherichia coli - Dec. 2012 THE JAPANESE JOURNAL OF ANTIBIOTICS 65 6 365 11 sita oxacin 1 1 1 1 1 1 2 2 3 3 1 1 1 2 3 2012 9 14 sita oxacin STFX 50 mg 10% 2008 1 2008 12 2010 11 2 STFX 1,452 91.4% 1,235/1,351 95.9% 466/486

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