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1 Treatment and Prophylaxis of Spontaneous Bacterial Peritonitis (1); (2), (3). (1) (2) (3) :, :,

2 Clinical Question 1 72...,.,,.,...

3. CT..,.

4? SBP? SBP.

5 Clinical Question SBP? SBP,?

6 SBP (Spontaneous Bacterial Peritonitis or primary peritonitis). and/or > 250/ul.. Runyon, et al. Clin Infect Dis. 1998;27:669-76.

7

8 : SBP 3, GPC

9 SBP Bacterial Translocation SBP Modified from Arroyo, et al. Infection;1994:22(3):167-75.

10 SBP. > > >,. ( ). ( ). Levison, et al. Chapter 76. Peritonitis and Intraperitoneal Abscess. Mandell, Douglas, and Bennett s Principles and Practice pf Infectious Diseases. 8th edition. 2015. New York. Elsevier.

SBP 1 g/dl (1) SBP : HR 3.43 [95%CI 0.63-0.93] (2), -1 69% (3) (4) PPI : HR 1.72 [1.10-2.69] (2) 1. Runyon. Gastroenterology. 1986;91(6):1343. 2. Dam et al. Hepatology. 2016;64(4):1265-72.. 3. Tito, et al. Hepatology. 1988;8(1):27. 4. Rimola, et al. Hepatology. 1985;5(3):463. 11

SBP & (1).,,,, etc (2). 46% (2). 30%, (3). (4). SBP 60% (5). 1. Hoefs, et al. Hepatology. 1982;2:399-407. 2. Carey, et al. Am J Gastroenterol. 1986;81:156-61. 3. Runyon, et al. Hepatology. 1990;12:710. 4. Runyon, et al. Hepatology. 2013;57:1651. 5. Chinnock, et al. J Emerg Med. 2013;44(5):903-9. 12

SBP,,. :,,,TP, LDH, Glc (1). Alb (SAAG), Amy ( ) (1) : 43% (2). 10 ml : 93%(2). (3). 1. Akriviadis, et al. Gastroenterology. 1990;98(1):127. 2. Runyon, et al. Gastroenterology. 1988;95(5):1351. 3. Runyon, et al. Clin Microbiol. 1990;24:1035-47. 13

SBP : : 50% (1) : 100% (2). (, Level A.) (3) 1. Nousbaum, et al. Hematology. 2007;45:1275-81. 2. Meddler, et al. J Hepatol. 2010;53:477-83. 3. 2015 ( 2 ). 14

15 SBP 239 SBP. :12 or 72. 72 2.7. Kim, et al. Am J Gastroenterol. 2014 Sep;109(9):1436-42.

16 SBP : Classic SBP: 250/ul. Culture-negative neutrocytic ascites (CNNA): 250/ul. Monomicrobial non-neutrocytic bacterascites (MNB): 250/ul. Modified from Bhuva, et al. Am J Med. 1994;97:169-75.

17 SBP : CNNA Culture-negative neutrocytic ascites (CNNA): 250/ul. SBP 250/ul, SBP (1,2). classic SBP CNNA (3). 1. Runyon, et al. Management of Adult Patients with Asictes Due To Cirrhosis: Update 2012. AASLD practice guideline.. Hepatology. 2013;57(4):1651. 2. Runyon, Hoefs. Hepatology. 1984;4(6):1209. 3. Pelletier, et al. J Hepatic. 1990;10(3):327.

SBP : MNB Monomicrobial non-neutrocytic bacterascites (MNB): 250/ul., 62% (1). MNB,, (2, 3, 4)., (2, 3, 4). 1. Runyon. Hepatology. 1990;12:710-715. 2. Pelletier, et al. Hepatology. 1991;14(1):112-5. 3. Runyon, et al. AASLD practice guideline. Management of Adult Patients with Asictes Due To Cirrhosis: Update 2012. Hepatology. 2013;57(4):1651. 4. Levison, et al. Chapter 76. Peritonitis and Intraperitoneal Abscess. Mandell, Douglas, and Bennett s Principles and Practice pf Infectious Diseases. 8th edition. 2015. New York. Elsevier. 18

SBP : MNB MNB (i.e. ), SBP classic SBP (1, 2, 3, 4). (3, 4). 1. Runyon. Hepatology. 1990;12:710-715. 2. Pelletier, et al. Hepatology. 1991;14(1):112-5. 3. Runyon, et al. AASLD practice guideline. Management of Adult Patients with Asictes Due To Cirrhosis: Update 2012. Hepatology. 2013;57(4):1651. 4. Levison, et al. Chapter 76. Peritonitis and Intraperitoneal Abscess. Mandell, Douglas, and Bennett s Principles and Practice pf Infectious Diseases. 8th edition. 2015. New York. Elsevier. 19

20 SBP 250/ul? SBP? YES NO YES classic SBP CNNA de-escalation empiric therapy 5 5. NO SBP YES SBP YES MNB 250/ul or? NO? NO Runyon, et al. Management of Adult Patients with Asictes Due To Cirrhosis: Update 2012. AASLD practice guideline. Hepatology. 2013;57(4):1651. YES SBP NO

21 2,.,. SBP,. Soriano, et al. J Hepatic. 2010;52(1):39-44.

22 2 1. 250/ul. /ul. 2., (polymicrobial pattern. ). 3. 2 : 1 g/dl, LDH, 50 mg/dl 2. and/or 3. 96% 2. 3. 67%, 90%. 2, 85% CT. Soriano, et al. J Hepatic. 2010;52(1):39-44.

23 2 CEA 5 ng/ml ALP 240 U/L : 2 ( 92%, 88%). 2. Wu, et al. J Hepatic. 2001;34:215-21.

2 250/ul ( 96%) (1). 1. polymicrobial pattern. 2. 2 ( 50%) (1): 1 g/dl, LDH, 50 mg/dl. YES NO? SBP YES NO 48 2 2 NO? YES. (1) Soriano, et al. J Hepatic. 2010;52(1):39-44. (2) Runyon, et al. AASLD practice guideline. Management of Adult Patients with Asictes Due To Cirrhosis: Update 2012. Hepatology. 2013;57(4):1651. (3) Runyon, et al. Spontaneous bacterial peritonitis in adults: Diagnosis. UpToDate. updated on 17 Aug, 2015. UpToDate, Inc. (4) Akriviadis, et al. Gastroenterology 1990;98:127-33. 24? YES NO SBP

25 SBP : SBP.,,., >250/ul SBP., 48. Runyon, et al. AASLD practice guideline. Management of Adult Patients with Asictes Due To Cirrhosis: Update 2012. Hepatology. 2013;57(4):1651.

SBP β (,, ) (1) 1 g q24 hr, 2 g q8hr (2). 500 mg IV/PO q24hr (2). 1.5 kg/day. 1 g/kg 3 (1, 2). 5-7 (1,2). de-escalation ( ). 1. Mandofer, et al. Gastroenterology. 2014 Jun;146:1680-90. 2. Carpenter. Peritonitis, Spontaneous Bacterial & Secondary. The Johns Hopkins POC-IT ABX Guide. 2013. Jones and Bartlett. 26

27 SBP β β. - -, - - Mondefer, et al. Gastroenterology. 2014. Jun;146(7):1680-90.

28 SBP :, (1). 6 1.5 g/kg, 3 1.0 g/kg (1). Cre 1 mg/dl, BUN 30 mg/dl, or T-Bil 4.0 mg/dl (2). (3). 1. Sort, et al. N Engl J Med. 199;341:403-409. 2. 2. Runyon, et al. AASLD practice guideline. Management of Adult Patients with Asictes Due To Cirrhosis: 3. Update 2012. Hepatology. 2013;57(4):1651. 4. 3. Sigal. et al. Gut. 2007;56: 597-599.

29 SBP : ( 2 = 100%, Level A) (1). 60 kg 1.5 g/kg = 90 g (25%Alb 50 ml, 7 ). : SBP ( 1, Level A) (2). 1. 2015 ( 2 ). 2... 2015 ( 1 )

30 (1).,, β,, (Class IIa, Level C) (1). 48 2 (2). 1. Runyon, et al. AASLD practice guideline. Management of Adult Patients with Asictes Due To Cirrhosis: Update 2012. Hepatology. 2013;57(4):1651. 2. Akriviadis, et al. Gastroenterology 1990;98:127-33.

31 (expert opinion) 5, - 250/ul :. - : 2. - 250/ul : 48,. Runyon, et al. Spontaneous bacterial peritonitis in adults: Treatment and Prophylaxis. UpToDate. updated on 4 Jan, 2016. UpToDate, Inc.

32 SBP (1). 20-40% (2, 3). 1 69%, 1 70% (4). SBP (5). 1. Runyon. Clin Infect Dis. 1998;27:669 2. Navasa, et al. Gastroenterology. 1996;111(4):1011-14. 3. Runyon, et al. Gastroenterology. 1991;100(6):1737-42. 4. Tito, et al. Hepatology. 1988;8:27-31. 5. Runyon, et al. Spontaneous bacterial peritonitis in adults: Treatment and Prophylaxis. UpToDate. updated on 4 Jan, 2016. UpToDate, Inc.

33 Clinical Question 2 65 C.. SBP,?

34 SBP SBP, (1)., (2). 1. Cohen, et al. Cochrane Databese of Systematic Reviews. 2009, Issue 2. 2. Ariza, et al. J Hepatol, 2012;56:825.

35 SBP (1) 1 2 (2).. UTI SBP. PPI. 1. Runyon, et al. Spontaneous bacterial peritonitis in adults: Treatment and Prophylaxis. UpToDate. updated on 4 Jan, 2016. UpToDate, Inc. 2. Runyon, et al. AASLD practice guideline. Management of Adult Patients with Asictes Due To Cirrhosis: Update 2012. Hepatology. 2013;57(4):1651.

AASLD : SBP :1 (Class I, Level A) (1). : 32%, 9.1% (2) 1. Runyon, et al. AASLD practice guideline. Management of Adult Patients with Asictes Due To Cirrhosis: Update 2012. Hepatology. 2013;57(4):1651. 2. Bernard. et al. Hepatology. 1999;29:1655-1661. 36

37 AASLD meta-analysis (1). gastrointestinal bleeding, (2). (3). 1. Bernard. et al. Hepatology. 1999;29:1655-1661. 2. Runyon, et al. AASLD practice guideline. Management of Adult Patients with Asictes Due To Cirrhosis: Update 2012. Hepatology. 2013;57(4):1651. 3. 2015 ( 2 ).

38 AASLD : SBP :1 <1.5 g/dl (Class I, Level A) (1, 2). a. (Cre > 1.2 mg/dl, BUN > 25 mg/dl or Na < 130 me/l) b. (Child-Pugh score 9 T-Bil 3 mg/dl) : SBP OR 0.18 [95%CI 0.10-0.32], OR 0.60 [0.37-0.97] (2). 1. Runyon, et al. AASLD practice guideline. Management of Adult Patients with Asictes Due To Cirrhosis: Update 2012. Hepatology. 2013;57(4):1651. 2. Loomba, et al. Clin Gastro Hep. 2009;7(4):487-493.

39 SBP 1 : RCT P: <1.5 g/dl + I: po C: placebo O: SBP,, SBP 7% 61% 1 Fernandez, et al. Gastroenterology. 2007;133:818-24.

40 SBP 1 : systematic review P: <1.5 g/dl 4 RCT I: C: vs. odds ratio [95% CI] SBP 0.18 [0.09-0.35] 0.18 [0.10-0.32] 0.60 [0.37-0.97] O: SBP,, Loomba, et al. Clin Gastro Hep. 2009;7(4):487-493.

SBP 1 : Cochrane Review Cohen, et al. Cochrane Databese of Systematic Reviews. 2009, 15;(2):CD004791.. 41

42 AASLD : SBP :2 SBP (Class I, Level A) (1). : 1 20%, 68% (2) 1. Runyon, et al. AASLD practice guideline. Management of Adult Patients with Asictes Due To Cirrhosis: Update 2012. Hepatology. 2013;57(4):1651. 2. Gines, et al. Hepatology. 1990;12(4 Pt 1):716.

43 SBP : : 1 g q24 hr 7 (1). : 400 mg po, ST DS po. - (Class IIb, Level C) (1, 2). - (expert opinion) (3). 1. Runyon, et al. AASLD practice guideline. Management of Adult Patients with Asictes Due To Cirrhosis: Update 2012. Hepatology. 2013;57(4):1651. 2. Terg, et al. Hepatology. 1996;24: 455A. 3. Runyon, et al. Spontaneous bacterial peritonitis in adults: Treatment and Prophylaxis. UpToDate. updated on 4 Jan, 2016. UpToDate, Inc.

44 ( 2 = 100%, Level A). < 1.5 g/dl 1, ( 2, Level A). SBP 2, ( 2, Level A). 2015 ( 2 ).

45 SBP : + /. :. : 3, : 1.. 2. SBP. 3.. : ST,.