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 2 1 2 3 1002 3g1 409.8 Nitrofurantoin Pivmecillinam E.coli 1/17
2 E.coli 30 85 32 1 G 1 NEJM 2 250 2 / 3 200 2 / 3 638.4 500 1 / 3 1547.1 3 7 3 3 513 2 500 2 / 1g/ / 7 750 / / 5 TMP80mg, SMX400mg 2 2 / 14 10 14 GM+AMPC UTI colonize UTI 12 15 34 5 32 UTI 85 95 2/17
E.coli reservoir 28 1 UTI 75 90 E.coli E.coli E.coli UPEC: Uropathogenic E.coli subset UPEC http://www.unitika.co.jp/upec/ UPEC Klebsiella pnumoniae Staph.saprophyticus Enterococcus faecalis Str.agalactiae Enterococcus faecalis Streptococcus agalactiae UTI UTI 1 UTI http://allabout.co.jp/gm/gc/298550/ D- mannose 3/17
http://www.suplinx.com/shop/goods/goods.aspx?goods=071-02811 D NEJM E.coli type1 pili FimH adhesin mannosylated receptor E.coli mannoside D-mannose adhesion blocker 38 CVA CVA esterase UTI 75 82 10 5 10 4 1 UTI NEJM 44 1. UTI 12 2. UTI 15 34 3. 32 UTI 4. 25 5. 28 1 6. UTI 7. 4/17
8. colonize 9. 10. 11. 12. UPEC 13. UPEC 14. UPEC 15. UTI UTI 1 sex 16. (+) CXCR1 IL8 17. UTI BMI. 18. E.coli 75 90 19. Klebsiella pn Staph.saproph Enteroc.faec Str.agalac 20. Enterococcus faec Str.agalac 21. 22. 38 CVA 23. 24. 25. 26. CVA 27. esterase UTI 75% 82% 28. 29. 30. 10 5 /ml 31. 10 4 32. 33. 2010 IDSA 34. 2T2 / 3 3g1 35. 36. 37. 7 5 14 38. 10 14 39. 10 14 40. GM+AMPC 5/17
41. 1 1 42. 43. 85 95 44. 1T1 Uncomplicated Urinary Tract Infection NEJM March15,2012 H24.3 Thomas M. Hooton, M.D. 30 2 dysuria (urinary urgency) vaginal irritation (vaginal discharge) 1 trimethoprim-sulfamethoxazole 1 3 The Clinical Problem a. 2007 860 84 12 32 1 0.70 / / 0.07 / / 6 25 acute uncomplicated pyelonephritis 28 1 15 34 1 25 b. uncomplicated complicated 6/17
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
IL8 receptor CXCR1 P1 e. E.coli 75 90 Klebsiella pneumoniae Staphylococcus saprophyticus Enterococcus faecalis Streptococcus agalactiae (Group B streptococcus) Enterococcus faecalis Streptococcus agalactiae 2. Strategies and Evidence a. 38 CVA 50 90 CVA dipsticks esterase nitrites nitrate ( ) nitrite ( ) 8/17
esterase nitirites UTI 75 82 UTI 10 5 /ml 30 50 10 2 4 10 4 /ml no growth b. 25 42, 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
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 / 3 3 93 90-100 1 dose TMP80mg-SMX400mg 2 1 2 3 TMP-SMX 30 85 Fosfomycin trometamol 3g 250 500 / 3g1 91 Nitrofurantoin 100mg 2 / 5 5 93 84 95 Pivmecillinam 400 2 / 3 7 3 7 73 55 82 short-course regimens 5 ecologic adverse effects 10/17
NSAID 2 90 85 98 Ciprofloxacin 250mg2 / 3 100 200 / Levofloxacin 250mg/500 1 / 3 3 7 89 79 98 d. 1 11/17
Ciprofloxacin 500 2 / or 1g/ / 7 Ciprofloxacin: 100 200 / 500 2 / 7 96 Levofloxacin 750 / / 5 Levofloxacin 250 500 / Levofloxacin 750 / / 5 86, Ciprofloxacin 500mg 2 / 81 Ciprofloxacin Levofloxacin TMP-SMX( )160-800 2 / 14 TMP80mg,SMX400 83 E.coli 92 35 E.coli 20 FDA IDSA 14 7 10 10 14 TMP-SMX fluoroquinolones e. CT 48 72 bacteremia 12/17
10 14 Ciprofloxacin 400 2 / 200 /150ml 300 /150ml Levofloxacin 500 750 1 / 500mg/20ml 500mg/100ml Ceftriaxone 1 2g 0.5g 1g Cefepime 1g 2 / 0.5g 1g Piperacillin-tazobactam 3.375g 6 2.25g 4.5g Meropenem 500mg 8 0.25g 0.5g Imipenam-cilastatin 500mg 6 8 0.25g, 0.5g Doripenem 500mg 8 0.25g 0.5g Ertapenem 1g1 1 Gentamycin 5-7 / 1 1 1-2g 6 f. 1 2 1 1 2 2 / 3 3g1 6 TMP-SMX( ) 1 QOL 13/17
g. diaphragm( ) Cranberry juice E.coli type1 pili FimH adhesin mannnosylated receptor E.coli mannoside D-mannnose adhesion blocker OTC 1 85 90 95 1 3 2 1 1 TMP80mgSMX400 1 0.3 / / 3.6/ / Cephalexin( 250 )1 Nitrofurantoin 50 100 1 TMP40mgSMX200mg ( ) 3 14/17
Cephalexin ( )125 250 1 Fosfomycin 3g10 Nitrofurantoin 50 100 h. CT 48 72 2 30 2 dysuria (urinary urgency) vaginal irritation (vaginal discharge) 1 trimethoprim-sulfamethoxazole 1 3 TMP-SMX 3 Nitrofurantoin 5 phenazopyridine 3 / OTC 15/17
1. UTI 12 2. UTI 15 34 3. 32 UTI 4. 25 5. 28 1 6. UTI 7. 8. colonize 9. 10. 11. 12. UPEC 13. UPEC 14. UPEC 15. UTI UTI 1 sex 16. (+) CXCR1 IL8 17. UTI BMI. 18. E.coli 75 90 19. Klebsiella pn Staph.saproph Enteroc.faec Str.agalac 20. Enterococcus faec Str.agalac 21. 22. 38 CVA 23. 24. 25. 26. CVA 27. esterase UTI 75% 82% 28. 29. 30. 10 5 /ml 16/17
31. 10 4 32. 33. 2010 IDSA 34. 2T2 / 3 3g1 35. 36. 37. 7 5 14 38. 10 14 39. 10 14 40. GM+AMPC 41. 1 1 42. 43. 85 95 44. 1T1 17/17