Spontaneous Bacterial Peritonitis(SBP)

Dr.Chakravarthy,P.S,MD

PG in Gastroenterology, AMC/KGH

OVERVIEW

• Definitions & Classification• Etiology & Pathophysiology• Clinical features• Investigations• Treatment • Prognosis• Prevention

CLASSIFICATION

Spontaneous asc.fluid infection• SBP• MNB• CNNA

Secondary bacterial peritonitis

Gut perforation/ non perforation

Polymicrobial bacterascites

DEFINITIONS

SBP

An infection of initially sterile ascitic fluid without a detectable, surgically treatable source of infection

Conn HO, 1969

• A positive ascitic fluid culture (essentially always a monomicrobial infection) +

• elevated ascitic fluid absolute PMN count (i.e.,

≥250 cells/mm3)

without an evident intra-abdominal source of infection that requires surgical treatment

DEFINITIONS

MNB

• a positive ascitic fluid culture for a single organism +

• an ascitic fluid PMN count lower than 250 cells/mm3 +

• no evidence of an intra-abdominal surgically treatable source of infection

DEFINITIONS

CNNA• the ascitic fluid culture grows no bacteria +• the ascitic fluid PMN count is 250 cells/mm3 or

greater +• no antibiotics have been given (not even a

single dose) +• no other explanation for an elevated ascitic

PMN count

DEFINITIONS

Secondary bacterial peritonotis

• ascitic fluid culture positive (usually for multiple organisms) +

• PMN count is 250 cells/mm3 (0.25 × 109/L) or greater +

• an intra-abdominal surgically treatable primary source of infection

DEFINITIONS

Polymicrobial bacterascites

• Multiple organisms are seen on Gram stain or cultured from the ascitic fluid +

• PMN count is lower than 250 cells/mm3 (0.25 × 109/L)

Incidence

• 20% of all cirrhotics

• 50% at admission, 50% during hospital stay

• Cirrhosis and ascites carry a 10% annual risk of ascitic fluid infection

• Of patients with cirrhosis who have SBP, 70% are Child-Pugh class C

ETIOLOGY

PATHOPHYSIOLOGY

• Spontaneous variants of ascitic fluid almost exclusively in the setting of severe liver disease

• Liver disease usually is chronic (cirrhosis), but may be acute (fulminant hepatic failure) or subacute (alcoholic hepatitis)

CNNA results from• Previous antibiotic treatment• Inadequate amount of fluid inoculated• Spontaneously resolving SBP after clearing of all

bacteria

• Most of the spontaneous forms(upto 62%) resolve by themselves

Risk factors

• Paracentesis

• GI hemorrhage,UTIs

• Deficient AF bactericidal activity (AF total protein <1 g/dl, and/or AF C3 <13 mg/dl)

• Previous episode(s) of SBP

CLINICAL FEATURES

Diagnosis• High index of suspicion• Low threashold for paracentesis• Clinical deterioration

• A clinical diagnosis without a paracentesis is

inadequate

Diagnostic Paracentesis

• All patients with ascites admitted to hospital as well as in cirrhotics

• Signs of abdominal or systemic infection (abdominal pain or tenderness, disturbed intestinal function, fever, acidosis, peripheral leukocytosis)

• Patients presented with encephalopathy or worsened renal functions.

AASLD,2013 guidelines(Class 1 ,Level B evidence)

ESSENTIALS OF PARACENTESIS

• ‘Skin needle’ to be replaced by sterile needle

• Blood culture bottles to be inoculated (atleast 10ml of fluid)

• Cell count sample to be inoculated into EDTA container

• Cell count to be done manually(not on autoanalyzers)

EASL 2010 guidelines for SBP

Ascitic fluid analysis

• Total count• Differential count• Absolute PMN count• Albumin • Culture and sensitivity

Ascitic fluid culture

• Positive in upto 40% cases• Most commonly – Gm neg.bacteria(E.coli) & Gm

positive cocci(Streptococcus)• 30% GNBs resistent to quinolones & 30% to

trimethoprim-sulphamethoxazole• Low resistance to 3rd gen.cephalosporins

Ascitic fluid culture

• Among culture positive samples,

2/3rd neutrocytic(SBP) &

1/3rd non-neutrocytic(MNB)

• Sec.BP 0% to 20% cases

• Polymicrobial 1 in 1000 samples

Ascitic fluid analysis• Total protein – risk of SBP

• Glucose – PMN activity

(>50mg/dl in SBP, <50 in Sec.BP)

• LDH – 43+/- 20mU/ml(sterile fluid)

• Bilirubin – only for orange/brown fluid

> serum level (or) >6mg/dl viscus

perforation

• PMN > 250/Cmm + high suspicion of Sec.BP

test for asc.fluid total protein,glucose, LDH,ALP & CEA

AASLD 2013,(Class 2A,Level B)

Leukocyte esterase (dipstick) test

• Efficacy of leukocyte esterase dipstick test as a rapid test in diagnosis of spontaneous bacterial peritonitis.

• Rerknimitr R, Rungsangmanoon W, Kongkam P, Kullavanijaya P.• Gastroenterology Unit, Department of Internal Medicine, Faculty of

Medicine, Chulalongkorn University, Bangkok• World J Gastroenterol. 2006 Nov 28;12(44):7183-7

• CONCLUSION:• Dipstick test can be used as a rapid test for screening of SBP. The

higher cut off colorimetric scale has a better specificity and positive predictive value but a lower sensitivity

Leukocyte esterase (dipstick) test

• Bedside leucocyte esterase reagent strips with spectrophotometric analysis to rapidly exclude spontaneous bacterial peritonitis: a pilot study.

• Gaya DR, David B Lyon T, Clarke J, Jamdar S, Inverarity D, Forrest EH, John Morris A, Stanley AJ.

• Department of Gastroenterology, Glasgow Royal Infirmary, Glasgow, UK.

• Eur J Gastroenterol Hepatol. 2007 Apr;19(4):289-95

• Conclusion :Bedside leucocyte esterase strips, spectrophotometrically read, can reliably exclude spontaneous bacterial peritonitis in patients with cirrhotic ascites. In our series, a negative strip result effectively ruled out this important condition, and suggests that the requirement for manual polymorphonuclear leucocyte counting in this setting could be removed

Leukocyte esterase (dipstick) test

• Review article: the utility of reagent strips in the diagnosis of infected ascites in cirrhotic patients.

• Nguyen-Khac E, Cadranel JF, Thevenot T, Nousbaum JB.• Hepato-Gastroenterology, Amiens University Hospital, CHU Nord,

place Victor Pauchet, France• Aliment Pharmacol Ther. 2008 Aug 1;28(3):282-8

• CONCLUSION:

Use of reagent strips for the diagnosis of SBP cannot be recommended, in view of low sensitivity and a high risk of false negatives, especially in patients with SBP and low polymorphonuclear count.

Ascitic fluid Lactoferrin

• Ascitic Fluid Lactoferrin for Diagnosis of Spontaneous Bacterial Peritonitis

• Mansour A. Parsi, Sherif N. Saadeh, Nizar N. Zein, Gary L. Davis• Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA• Gastroenterology,Volume 135, Issue 3 , 803-807, September 2008

• Conclusions: AFLAC can serve as a sensitive and specific test for diagnosis of SBP. Qualitative bedside assays for the measurement of AFLAC can be developed easily and may serve as a rapid and reliable screening tool for SBP in patients with cirrhosis

Granulocyte elastase• Rapid detection of spontaneous bacterial peritonitis by

granulocyte elastase latex immunoassay and reagent

strip.• Yamazaki M, Sano R, Kuramoto C, Yoshiji H, Uemura M, Fukui H, 

Kamiya M, Okamoto Y.• Central Clinical Laboratory, Nara Medical University Hospital,

Kashihara 634-8522, Japan• Rinsho Byori. 2011 Jun;59(6):549-58• Results :The sensitivity, specificity, and positive and negative

predictive values of the reagent strips for diagnosis of SBP were 92.9%, 90.9%, 76.5%, and 97.6%, respectively.

• Conclusion : GE-LIA reagent strips are rapid and sensitive and can aid diagnosis of SBP.

• Imaging

rarely required for SBP

useful for Sec.BP

Differential diagnosis

• Tuberculosis • Acute pancreatitis• Peritoneal carcinomatosis• Peritoneal hemorrhage

TREATMENT

Ideal timing to treat….

As early as possible …..if• Temperature >37.8*C(100*F)• Abdominal pain/ tenderness• Altered mental status • Start empirical i.v antibiotic (broad-spectrum)

+ supportive measures

AASLD2013,(Class 1, Level A)

Which drug to start with…?

• Third generation cephalosporin

(preferably cefotaxime 2gm,IV, 8th hourly)

AASLD 2013,(Class 1, Level A)

• Ofloxacin 400mg 12th hourly

AASLD 2013,(Class 2A,Level B)

(exclude prior exposure to quinolones,vomiting,shock,creat>3mg/dl, Gr.II or more encephalopathy prior to therapy)

TREATMENT

• PMN<250 + symptoms/signs of infection

should receive empiric antibiotic

(till the culture report)

AASLD 2013,(Class 1, Level B)

TREATMENT

• PMN > 250/cmm + clinical picture suggestive

treat just like classical SBP (irrespective of

culture report)

EASL 2010 guidelines for SBP

TREATMENT

• Albumin ..?

1.5gm/kg body wt within 6hrs of detection

&

1.0gm/kg body wt on 3rd day

(PMN>250, Creat>1mg/dl, BUN>30mg/dl ,

total bilirubin>4mg/dl)

AASLD 2013,(Class 2A, Level B)

• Albumin Infusion Improves Outcomes of Patients With Spontaneous Bacterial Peritonitis: A Meta-analysis of Randomized Trials.

• Salerno F, Navickis RJ, Wilkes MM.• Dipartimento di Medicina Interna, Università degli Studi di Milano,

Policlinico IRCCS San Donato, Milano, Italy.• Clin Gastroenterol Hepatol. 2013 Feb;11(2):123-130

CONCLUSIONS:

In a meta-analysis of 4 RCTs (288 patients), albumin infusion prevented renal impairment and reduced mortality among patients with SBP

Clinical Gastroenterology and hepatology,2012,Vol.10,No.3

Repeat paracentesis

• Clinical deterioration – fever, abd.pain, renal failure,altered mental

status,GI bleed,peripheral leukocytosis

Predictors of poor outcome

• Age >60yr• Community Vs hospital acquired SBP• S.creatinine >3mg/dl• BUN > 30mg/dl• Child – Pugh score >9

PROGNOSIS

• <5% mortality (48-95% in the past)

• Mortality in cured pts is d/t worsening of underlying liver disease/ GI bleeding

• 100% mortality in Sec.BP without surgery• 50% mortality with laparotomy

PREVENTION

• IV Ceftriaxone/oral Norfloxacin BD for 7days in all GI beeds with cirrhosis (Class 1,Level A)

• Daily norfloxacin (longterm) in survivors of SBP

(Class 1,Level A)

AASLD 2013

• Cirrhosis & ascites but no GI bleed

longterm Norfloxacin indicated if asc.fluid total protein < 1.5gm/dl & one of the following present

- S.creatinine >/= 1.2mg/dl

- BUN >/= 25mg/dl

- S.Na+ </= 130meq/L

- CTP score >/= 9

AASLD 2013 (Class1 ,Level B)

• Primary Prophylaxis of Spontaneous Bacterial Peritonitis Delays Hepatorenal Syndrome and Improves Survival in Cirrhosis 

• Javier Fernández, Miquel Navasa• Gastroenterology, Volume 133, Issue 3, September 2007, Pages

818-824

Take Home message

• Infection of asc.fluid is often underdiagnosed• All admitted pts should undergo diagnostic

paracentesis• Meticulous care required while processing the

samples• Try to ruleout secondary causes in all possible

cases• Rapid bedside tests help in changing outcome

Take Home message

• Early antibiotic therapy grossly alters the final outcome

• Primary prophylaxis has a role in preventing systemic complications and improving survival

REFERENCES

• Sleisenger text book of GI and liver diseases,9th edition• Schiff’s diseases of the liver,11th edition• AASLD guidelines for ascites & SBP(2013)• EASL guidelines for ascites and SBP(2010)• Cochrane metaanalysis database for SBP treatment• Jour of clin gastroenterology and hepatology,Feb.2013• Gastroenterology,vol.133,Sept,2008• Aliment Pharmacol Ther. 2008 Aug