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Spontaneous bacterial peritonitis (SBP)

Discuss the pathogenesis of SBP?

  • Portal hypertension leads to intestinal oedema and sluggish movement leading to bacterial overgrowth.
  • This leads to bacterial translocation in presence of increased capillary permeability.
  • The bacteria seed the mesenteric lymph nodes and then it goes to lymphatic or to systemic circulation and ultimately comes to ascitic fluid.
  • The bacteria cannot be phagocytosed by local macrophages and neutrophil because of lack of opsonisation caused by low complement levels in cirrhotic patients. (Ascitic fluid <10gm/L indicates high chance of having SBP)

What is SBP?

  • Monomicrobial infection of ascitic fluid in absence of contagious source of sepsis.
  • It is confirmed by positive bacterial culture of the ascitic fluid and ascitic fluid neutrophil count of >250cells/mm3
  • Occurs in the background of advanced cirrhosis, particularly when ascitic fluid protein goes below 10gm/L
  • Usual source is gut bacteria but may be secondary to bacteraemia from UTI/ dental abscess/ cellulites etc

What is secondary bacterial peritonitis?

  • Polymicrobial infection of ascitic fluid in presence of surgically treatable source of sepsis.
  • It is confirmed by positive bacterial culture of the ascitic fluid and ascitic fluid neutrophil count of >250cells/mm3 (in contrast to SBP neutrophil count is normally >1000cells/mm3)
  • Two types: perforation peritonitis- rupture of bowel/stomach and non perforation peritonitis – perinephric abscess

Discuss the incidence and prognosis of SBP?
SBP occurs in 10-30% of cirrhotic hospitalised patients

Untreated mortality is 90% which is reduced to 20% with early diagnosis and prompt treatment.

When to suspect SBP?

Any cirrhotic ascites on admission to hospital for any reason should have a diagnostic tap.

Any known cirrhotic with ascites with fever, abdominal pain, confusion, encephalopathy, abdominal tenderness or diarrhoea or developing renal failure should have diagnostic tap.

Risk factors for SBP in cirrhotic:

Low ascitic fluid protein
On PPI
Malnutrition
GI bleeding

Does it matter if fluid is sent in EDTA bottle or normal bottle for cell count?

Yes. The sample if clotted will give a false negative result if sent in a white top universal container.

How to diagnose by ascitic fluid analysis?

  • Send EDTA sample 1ml for cell type and differential count- ask lab to bleep with the result
  • Normally done by on call microbiology technician rather than automated coulter counter which can be inaccurate in this low level of neutrocytois ( 0.25×109 /L in ascitic fluid as opposed to normal blood WBC of 10×109 /L)
  • A neutrophil count of >250 cells/mm3 is confirmatory.

Does it matter if fluid is sent in blood culture bottle or normal bottle?

Yes, inoculation at bed side in blood culture bottle will yield positive culture in 72-90% of cases of SBP as opposed to only 40% if culture is sent in white topped sterile universal container (which is the common practice)

Is Gram stain necessary?

Rarely helpful in SBP and BSG does not recommend requesting it.

What is bacterascites?

Ascitic fluid which is culture positive but with normal neutrophil count.

What is CNNA?

Culture negative neutrocytic ascites should be treated exactly as SBP as they have similar morbidity and mortality.

Do they need repeat tap to make sure the count is improving?

If repeat tap after 48hrs does not show reduction in the neutrophil count to >25% of the pre-treatment value – implies treatment failure. Antibiotic should be changed. This is important particularly if patient is still symptomatic and not improving.
Why it is important to differentiate SBP from secondary BP?

The patients of secondary BP will die almost 100% in spite of antibiotic in absence of surgery

The patients of SBP will have 80% mortality if they have unnecessary laparotomy.

How to differentiate from secondary BP?

Neutrophil count: normally in hundreds in SBP and in thousands in Secondary BP

Sugar: <2.8 mmol/L in Secondary BP because high numbers of neutrophil consume sugar and in frank perforation sugar level can be zero

Protein: low (<10g/L) in SBP, higher in Secondary BP
LDH: High in secondary BP greater than the upper limit of normal for serum

Microbial flora on culture/Gram stain: polymicrobial in secondary BP. Gram stain is normally negative in SBP and shows polymicrobial flora in secondary BP. Even then Gram stain is not recommended.

CEA: High levels in secondary BP
ALP: High levels in secondary BP

Also Erect CXR shows gas under diaphragm/ gastrograffin enema shows extravasation of contrast into the peritoneum.

What are the differentials of Secondary BP?

Late presentation of SBP, SBP treated with resistant antibiotic, peritoneal carcinomatosis and tubercular peritonitis can masquerade as secondary BP with very high WBC count and low ascitic fluid sugar and high LDH.

What is the microbiological flora?

In 70% of cases it is – either E.Coli, Streptococcus or enterococcus

Which antibiotic to start treatment?

Any third generation antibiotic which is sensitive to the microbiological flora and good penetration to ascitic fluid is good. Most studied antibiotic is cefotaxime- 2g BD for 5days is the BSG recommendation.

Other alternatives are ceftriaxone, ceftazidime or co-amoxiclav.

Oral treatment works?

Asymptomatic patients with good bowel sound can be treated with oral ciprofloxacin (750mg BD) or co-amoxiclav (1.2g TDS)

Is there any role of primary prophylaxis?

Some centres suggest primary prophylaxis when ascitic fluid protein is lower than 10gm/L but no consensus and currently no good evidence to suggest its use.

Discuss secondary prophylaxis?

After first episode of SBP approx 70% of the patients will have recurrence at the end of one year.

Should be given secondary prophylaxis with Norfloxacin 400mg OD or ciprofloxacin 500mg OD- reduces the probability of recurrence of SBP from 68% to 20%

Does it precipitate renal failure?

Development of renal failure occurs in 30% of patients of SBP and is one of the strongest predictors of mortality in SBP.

Is there any use of albumin in SBP?

BSG supports the recommendations of the Barcelona group of infusing albumin (1.5gm /Kg on Day 1 and 1gm/Kg on Day 3) in SBP in patients with high creatinine or rising creatinine but does not support routine use.

Is it indication for referral to transplant centre?

Yes.
Probability of survival at one year after an episode of SBP is 30-50% which falls to 25-30% at two years. So patients recovering form SBP should be referred to transplant centre for consideration of liver transplant, if clinically appropriate.

Ref

British Society of Gastroenterology guidelines for the management of ascites in cirrhosis

  1. SBP is confirmed by positive bacterial culture of the ascitic fluid and ascitic fluid neutrophil count of >500cells/mm3 – False ( >250 neutrophils /mm3)
  2. Occurs in the background of advanced cirrhosis, particularly when ascitic fluid protein goes below 20mg/L – FALSE (below 10mg/L)
  3. Usual source is gut bacteria - TRUE
  4. occurs in 5-10% of cirrhotic hospitalised patients – FALSE – 10-30%
  5. Untreated mortality is 90% – TRUE
  6. GI bleeding is a risk factor for SBP in cirrhotic pts - TRUE
  7. The commonest symptom in SBP is confusion – FALSE (Fever> abdominal pain> confusion)
  8. Gram stain a useful diagnostic test - FALSE
  9. Neutrophil  count: normally in hundreds in SBP and in thousands in Secondary BP - TRUE
  10. Sugar: >2.8 mmol/L in Secondary BP – FALSE ( Sugar is <2.8mmol/L as neutrophils consume sugar)
  11. The microbiological flora is usually either E.Coli, Streptococcus or enterococcus – TRUE
  12. Primary prophylaxis is often indicated when protein is lower than 10gm/L – FALSE
  13. After first episode of SBP approx 70% of the patients will have recurrence at the end of one year. – TRUE
  14. Development of renal failure occurs in 70% of patients of SBP – FALSE (in 30%)
  15. Patients recovering from SBP should be referred to transplant centre – TRUE

Take home message:

Suspect SBP when—- ascites with cirrhosis

+ fever or
abdominal pain or
confusion or
abdominal tenderness or
diarrhoea or
renal failure

Ascitic tap-

  1. Neutrophils>250cells/mm3 (send in EDTA tube not white top container)
  2. Culture (send in blood culture bottle not white top container)
  3. Protein <10g/L
  4. Sugar – near normal

Exclude secondary bacterial peritonitis

  1. Neutrophil  count: normally in hundreds in SBP and in thousands in Secondary BP
  2. Sugar: <2.8 mmol/L in Secondary BP because high numbers of neutrophil consume sugar and in frank perforation sugar level can be zero
  3. Protein: low (<10g/L) in SBP, higher in Secondary BP
  4. LDH: High in secondary BP greater than the upper limit of normal for serum
  5. Also Erect CXR shows gas under diaphragm/ gastrograffin enema shows extravasation of contrast into the peritoneum.

Start cefotaxime 2g bd x 5 days
Change later depending on sensitivities

Asymptomatic patients with good bowel sound can be treated with oral ciprofloxacin (750mg BD) or co-amoxiclav (1.2g TDS)

Prevention of ARF
BSG supports the recommendations of the Barcelona group of infusing albumin (1.5gm /Kg on Day 1 and 1gm/Kg on Day 3) in SBP in patients with high creatinine or rising creatinine but does not support routine use.

After an attack of SBP

  1. Refer patient for consideration of transplant- Probability of survival at one year after an episode of SBP is 30-50%
  2. Patient should be given secondary prophylaxis with Norfloxacin 400mg OD or ciprofloxacin 500mg OD- reduces the probability of recurrence of SBP from 68% to 20%

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