慈恵ICU勉強会 2013 - jseptic.com

1 Clostridium difficile ICU 2013 10 8 1 Pseudomembraneous coli8s Clostridium difficile associated diarrhea (CDAD) CD Clostridium difficile coli8s (CDC) CD ( ) Clostridium difficile enteri8s CD Clostridium difficile infec8on (CDI) CD 2 2000 CDI 3 4 5 6 7 All- Cause and Disease- Specific Mortality in Hospitalized Pa:ents With Clostridium difficile Infec:on: A Mul:center Cohort Study Clin Infect Dis. 2013;56:1108. CDI 30 ~1 ICU 48 CDI CDI ( vs. , P= ) CDI ( vs. , P< ) CDI (23 vs. 15 , P< ) ICU (12 vs. 8 , P< ) 8 Clostridium difficile Infec:on: A Mul:center Study of Epidemiology and Outcomes in Mechanically Ven:lated Pa:ents Crit Care Med.

2 2013;41:1968. CDI Non- CDI 48 5852 386 ( ) CDI Sep8c shock CDI 6 15 Health care CDI coloniza8on 9 Host and Pathogen Factors for Clostridium difficile Infec:on and Coloniza:on N Engl J Med 2011;365:1693. Agenda Introduc8on Mild, moderate, severe CDI Severe and complicated CDI CDI CDI 10 Agenda Introduc8on Mild, moderate, severe CDI Severe and complicated CDI CDI CDI 11 GRADE system Am J Gastroenterol 2013;108:478. IF= 12 SHEA & IDSA 2010 & 2010 Severity Criteria Mild- to- moderate disease ~ WBC 15,000/ L Cr Severe disease WBC 15,000/ L Cr Severe and complicated disease OR OR OR megacolon Recurrent CDI CDI 13 Infect Control Hosp Epidemiol.

3 2010;31:431. ACG 2013 2013 Severity Criteria Mild- to- moderate disease ~ + Severe disease Alb<3g/dL + : WBC 15,000/ L Severe and complicated disease : CDI ICU ( ) WBC 35,000/ L, <2,000/ L Lac> ( , ,,,) Recurrent CDI CDI 8 CDI 14 Am J Gastroenterol 2013;108:478. ACG2013 Severe Cr Alb 15 Shigeki Fujitani, et al. Infect Control Hosp Epidemiol 2011;32:220. Comparison of Clinical Severity Score Indices for Clostridium difficile Infec:on Metronidazole 16 Metronidazole 1957 ( ) 1961 2005 7 2007 8 ( ) 2011 8 2012 3 17 Metonidazole ( =IDATEN HIV ) (2010 5 21 )

4 , 2012 8 , , , 18 Metronidazole 19 2012 8 CDI 20 Metronidazole Metronidazole (R- NO) DNA Bacteroides fragilis Clostridium difficile bioavailability 100% intact Vancomycin Metronidazole 21 Metronidazole Metronidazole- induced encephalopathy 22 7 ( ) 23 AJNR Am J Neuroradiol.

5 2007;28:1652. MR Imaging of Metronidazole- Induced Encephalopathy: Lesion Distribu:on and Diffusion- Weighted Imaging Findings Metronidazole (11- 52 ) : (N=7), (N=5), (N=2), (N=1), (N=1), (N=1) Metronidazole (4- 10 ) 24 AJNR Am J Neuroradiol. 2007;28:1652. mild, moderate, severe CDI 25 Recommenda8on CDI (empiric therapy) Strong recommenda8on, moderate- quality evidence Strong recommenda8on, high- quality evidence 26 Recommenda8on Mild- to- moderate CDI 500mg 1 3 10 Strong recommenda8on, high- quality evidence Severe CDI 125mg 1 4 10 Condi8onal recommenda8on, moderate- quality evidence 27 Metronidazole vs.

6 Vancomycin, Symptoma8c Cure minus recurrences Outcome = 80- 90 RCT outcome 2007 Zar RCT VCM 28 Cochrane Database Syst Rev. 2011 Sep 7;(9):CD004610. Background: Metronidazole Vancomycin RCT RCT Objec8ve: Mild severe CDI Vancomycin Metronidazole Design: a prospec8ve, randomized, double- blind controlled trial Semng: (200 ) 1994 10 ~2002 6 Pa8ents: (24 3 ) 48 CD Toxin A , OR mild severe Inclusion 2 severe >60 > < WBC>15,000 Interven8on: metronidazole ( 250 mg 1 4 ) 10 or Vancomycin ( 125 mg 1 4 ) 10 Measurements: Primary outcome day 6 day 6~10 Toxin A day 6 Toxin A 21 CD Toxin A 29 A Comparison of Vancomycin and Metronidazole for the Treatment of Clostridium difficile Associated Diarrhea, Stra:fied by Disease Severity Clin Infect Dis.

7 2007;45:302. Zar 2007 RCT Metronidazole vs. Vancomycin Severe Vancomycin Severe CDI Vancomycin Metronidazole 30 Clin Infect Dis. 2007;45:302. Zar 2007 RCT Metronidazole 250mg 1 4 2010 500mg 1 3 Toxin A assay Toxin day 6 10 Metronidazole Vancomycin day 10 31 52 Vancomycin 10 Metronidazole 2007 Zar RCT Day6 10 Metronidazole severe Vancomycin 32 Clin Infect Dis. 2008;47:56. Comparison of Clinical and Microbiological Response to Treatment of Clostridium difficile Associated Disease with Metronidazole and Vancomycin Recommenda8on Metronidazole 5- 7 125mg 1 4 Vancomycin Strong recommenda8on, moderate- quality evidence 33 !

8 ? Metronidazole CDI ( ) Metronidazole ( ) 34 Recommenda8on Mild- to- moderate CDI Metronidazole / / Vancomycin 125mg 1 4 Strong recommenda8on, high- quality evidence 35 Recommenda8on (Hartman ) Vancomycin Condi8onal recommenda8on, low- quality evidence Vancomycin 500mg 100- 500mL 6 severe and complicated CDI 36 Recommenda8on ( ) CDI CDI CDI CDI Strong recommenda8on, low- quality evidence 37 Systema8c review 20 (1 case reports case series) CDI 55 19 (35%) 9 (16%) 27 (49%) 17 (31%) colon 5 CDI Metronidazole Vancomycin 23 38 An:mo:lity Agents for the Treatment of Clostridium difficile Diarrhea and Coli:s Clin Infect Dis.

9 2009;48:598. Agenda Introduc8on Mild, moderate, severe CDI Severe and complicated CDI CDI CDI 39 Recommenda8on suppor8ve care ( VTE ) ( ) / Condi8onal recommenda8on, low- quality evidence 40 Recommenda8on Complicated CDI CT Condi8onal recommenda8on, low- quality evidence colon megacolon ( ) 41 39 CT CDI 39 CDI 0% CDI 48 6 ( ) Toxin assay ( ) Toxin assay : 3/33 ( ) vs. 3/15 (20%), P< 42 Ann Surg. 2002;235:363. Fulminant Clostridium difficile: An Underappreciated and Increasing Cause of Death and Complica:ons 43 39 ( ) colon colon Ann Surg.

10 2002;235:363. Recommenda8on Severe and complicated CDI Vancomycin 125mg 1 4 Metronidazole 500mg 1 3 Strong recommenda8on, low- quality evidence 44 Recommenda8on ( ) OR toxic coli8s AND/OR severe and complicated CDI Vancomycin 500mg 1 4 Vancomycin 500mg 500mL 1 4 Metronidazole 500mg 1 3 Strong recommenda8on, low- quality evidence 45 500mL Vancomycin Cl Cl 46 Recommenda8on CDI 1 ; Sepsis WBC 50,000/ L, Lactate 5mmol/L; 5 complicated CDI Strong recommenda8on, moderate- quality evidence 47 35~80% 48 Colectomy colectomy (OR ; 95%CI ; P< ) 49 Ann Surg 2007;245: 267.