Spontaneous bacterial peritonitis (SBP)

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Spontaneous bacterial peritonitis (SBP)

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SBP-Definition

• Peritoneal infections are classified as primary
  (ie, spontaneous), secondary (ie, related to a
  pathologic process in a visceral organ), or
  tertiary (ie, persistent or recurrent infection
  after adequate initial therapy).
• Spontaneous bacterial peritonitis is
  characterized by the spontaneous infection of
  ascitic fluid in the absence of an intraabdominal
  source of infection (e.g. intestinal perforation,
  abscess).
• (Genuit
  T., e-medicin august, 2002).

(Garcia-Tsao, Can J Gastroenterol. 2004)
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SBP-Definition

• Other spontaneous infections in cirrhotic
  patients are spontaneous bacterial empyema and
  spontaneous bacteremia (positive blood cultures
  in the absence of a source of infection). All
  have the same pathogenesis and should be managed
  in the same fashion.
• The most common is SBP with an incidence of
  approximately 10-30.

(Garcia-Tsao, Can J Gastroenterol. 2004)
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SBP-Aetiology

• Infection is blood-born and in 90 monmicrobial.
• The majority (70) of the cases are caused by
  organisms of the normal flora of the intestine,
  mainly aerobic gram-negative organisms with E.
  coli accounting for half the cases.
• The next most frequent microorganisms are
  gram-positive cocci, mainly Streptococcus sp
  (20) with enterococcus accounting for 5 of the
  cases.
• Infection with more than one organism is likely
  to be associated with abdominal paracentesis or
  intra-abdominal source of infection.
• 
  (Garcia-Tsao, Can J Gastroenterol. 2004
• 
  (Sheila Sherlock2002).
• 
  

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SBP-Aetiology

• A variety of abnormalities have been identified
  contributing to infection. Gastrointestinal
  bleeding, Increased colonization of the small
  bowel with prominent bacterial translocation,
  decreased opsonin function in both blood and
  ascites, impaired complement, leukocyte
  dysfunction, decreased antibodies and increased
  immunosuppressive cytokines, endotoxin, or tumor
  necrosis factor have been found in advanced liver
  failure.
• Invasive procedures, such as endoscopy or TIPS,
  the use of indwelling venous and urinary
  catheters are often immediate antecedents of
  infection
• 
  (Iber, American J
  Gastro 1999)

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SBP-Pathogenesis

• As cirrhosis develops in animals, gram-negative
  bacteria increase in numbers in the gut. The gut
  of patients with advanced cirrhosis is more
  permeable to bacteria than the normal gut and
  more permeable than the gut in less advanced
  cirrhosis.
• Once bacteria reach a critical concentration in
  the gut lumen, they "spill over", and escape the
  gut, "translocating" to mesenteric lymph nodes.
  Then they can enter lymph, blood, and eventually
  ascitic fluid.
• 
  
  (Runyon Gut 2004)
  
• 
  (Cirera, J
  Hepatol 2001)
• 
  (
  Runyon J Hepatol 1994)
• 
  
  

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SBP-Pathogenesis

• Peritoneal macrophages are the first line of
  defence against bacterial colonisation of ascitic
  fluid. SBP occurs when macrophages fail to kill
  the bacteria and the second line of defence is
  called in, the neutrophils.
• Opsonins assist motile and fixed killers of
  bacteria, the neutrophils and Kupffer cells,
  respectively. If the ability of the ascitic fluid
  to assist macrophages and neutrophils in killing
  the errant bacteria is deficient, uncontrolled
  growth occurs.
• The opsonic activity of the ascitic fluid is
  proportional to protein concentration and SBP is
  more likely if ascitic fluid protein is less than
  1 g/ dl.

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SBP-Pathogenesis

• Thus SBP is the result of failure of the gut to
  contain bacteria and failure of the immune system
  to kill the virulent bacteria once they have
  escaped the gut making patients with cirrhosis
  vulnerable to infection by their own gut flora.
• The recent molecular evidence of bacterial
  translocation shows patients with cirrhosis
  having bacterial DNA in their serum and ascitic
  fluid, and that DNA is always present
  simultaneously in both body fluids.
  
• 
  (Such Hepatology 2002
  Francés, Gut 2004)

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SBP-Pathogenesis

• Innate defenders against bacterial invasion
  include macrophages, dendritic cells, and natural
  killer cells. These cells synthesise
  proinflammatory cytokines and effector molecules,
  which assist in killing bacteria. Unfortunately,
  patients with advanced cirrhosis have been
  reported to have defects and dysfunction in many
  of these systems of protection.
• To make matters worse, some of the effector
  molecules and cytokines that help kill the
  bacteria have undesired side effects. NO and TNF
  are important mediators of vasodilation and renal
  failure that too often accompany SBP.
• Fiuza J Infect
  Dis 2000 Such, Eur J Gastroenterol Hepatol, 2004
  

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SBP-Diagnosis

• Early diagnosis and the initiation of prompt
  effective therapy have played key roles in
  decreasing the mortality associated with SBP. SBP
  should be suspected if a patient with known
  cirrhosis deteriorates.
• Ascitic fluid protein less than 1 g/ dl and
  height serum Bilirubin independently predict the
  first SBP. Patients with variceal bleeding or
  previous SBP are at particular risk.
• Patients may develop abdominal pain, tenderness,
  fever, and systemic leucocytosis, however these
  features may be absent and the diagnosis is made
  on the index of suspicion with examination of the
  ascitic fluid.

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SBP-Diagnosis

• A diagnostic paracentesis should be performed
• In any cirrhotic patient that develops compatible
  symptoms and/or signs of peritonitis
• In any cirrhotic patient who develops sudden
  unexplained deterioration in renal function or
  hepatic encephalopathy.
• In any patient with cirrhosis and ascites
  admitted to the hospital, independent of the
  presence or absence of compatible symptoms and/or
  signs of a peritoneal infection.

Rimola et al., Hepatology 1985 Garcia-Tsao, Can J
Gastroenterol. 2004
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SBP-Diagnosis

• The diagnosis is established with the finding of
  an ascites polymorphonuclear count (PMN) gt250/mm.
  
• Bacterial count in the ascites is low. Direct
  inoculation of routine blood culture bottles at
  the bedside with 10 cc of ascitic fluid has been
  reported to significantly increase the
  sensitivity of microbiologic studies
• Culture-negative neutrocytic ascites exists when
  the ascitic fluid cultures are negative yet the
  PMN count is gt500 cells/mm
• Bacterascites exists when a positive culture
  coexists with a nonelevated ascites PMN count.

(Caly J, Hepatol 1993Garcia-Tsao, Can J
Gastroenterol. 2004)
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SBP-Diagnosis

• . Blood cultures are positive in 33.
• An ascites lactate level of gt25 mg/dL was found
  to be 100 sensitive and specific in predicting
  active SBP in a retrospective analysis.
• The combination of an ascites fluid pH of lt7.35
  and PMN count of gt500 cells/mm3 was 100
  sensitive and 96 specific.
• A diagnostic thoracentesis should be performed in
  cirrhotic patients with new onset pleural
  effusion and in patients in whom SBP/infection is
  suspected but in whom there is no ascites or in
  whom the ascites PMN count is lt250/mm3

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SBP-Complication

• The most severe complication of spontaneous
  bacterial peritonitis is the hepatorenal
  syndrome, which occurs in up to 30 percent of
  patients and carries a high mortality rate.
• After resolution, SBP may recur, with an
  estimated 70 percent probability of recurrence at
  one year.
• (Sort et
  al. N Engl J Med 1999 GrangeJ et ai., Hepatol
  1998)

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SBP-Treatment

• A minimal duration of five days of parenteral,
  third-generation cephalosporin such as cefotaxime
  2 gm every 12 h is usually effective. Intravenous
  Amoxycillin-clavulanic acid is as effective as
  cefotaxime. Intravenous ciprofloxacin followed by
  oral treatment is also effective. These regimens
  are for initial empiric therapy and antibiotic
  choice should be reviewed once results of ascitic
  culture are known.
• 
  (Sheila Sherlock2002).

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SBP-Treatment

• A trial that investigated oral ofloxacin found it
  as effective as intravenous cefotaxime in the
  treatment of SBP. This trial identified a small
  subgroup of patients with SBP that had an
  excellent prognosis (100 SBP resolution and 100
  survival) and was characterized by having a
  community-acquired SBP, no encephalopathy and a
  BUN lt25mg/dL.

Navasa et al., Gastroenterology 1996
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SBP-Treatment

• Intravenous albumin (1.5 g per kilogram of body
  weight at diagnosis and 1 g per kilogram 48 hours
  later) significantly lower rates of renal
  dysfunction (10 vs. 33), hospital mortality
  (10 vs. 29) and 3-month mortality (22 vs. 41)
  compared to patients that did not receive
  albumin. The inpatient mortality rate of 10 is
  the lowest described so far for SBP.
• (Sort et al. N Engl J Med
  1999 Garcia-Tsao, Can J Gastroenterol. 2004)

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SBP-Treatment

• The group of patients that benefit from the
  addition of albumin was characterized by having a
  serum bilirubin gt4mg/dL and evidence of renal
  impairment at baseline (BUN gt30 mg/dL and/or
  creatinine gt1.0 mg/dL)13.
• This regimen is empirical, and no information
  exists on the efficacy of lower albumin doses or
  other plasma expanders.

(Ginès, N Engl J Med 2004 Garcia-Tsao,
Gastroenterology 2001- Garcia-Tsao, Can J
Gastroenterol. 2004)
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SBP-Treatment

• Diuretic therapy increases the total protein and
  ascitic opsonic activity.  
• Patients should be treated in the hospital until
  there is clear evidence of improvement,
  specifically resolution of symptoms/signs and a
  gt25 decrease in ascites PMN count in a follow-up
  (48-hour) paracentesis.  
• Spontaneous bacterial peritonitis is an
  indication to consider hepatic transplantation,
  particularly if recurrent.

Garcia-Tsao, Can J Gastroenterol. 2004
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SBP-Prognosis

• In initial series published in the 1970s, when
  the entity was first described, the mortality
  exceeded 80 studies in the early 1980s
  revealed an SBP mortality of 50 and in the early
  1990s, mortality had decreased to around 40.
• In more recent prospective studies with
  well-defined criteria for the diagnosis of SBP,
  the mortality rate was 20-30

Ricart et al J Hepatol 2000 Thuluvath Am J
Gastroenterol 2001 Garcia-Tsao, Can J
Gastroenterol. 2004 .
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SBP-Prophylaxis

• SHORT-TERM PRIMARY PROPHYLAXIS (PREVENTION OF
  BACTERIAL INFECTIONS IN PATIENTS WITH GI
  HEMORRHAGE)
• LONG-TERM SECONDARY PROPHYLAXIS (PREVENTION OF
  SBP RECURRENCE).
• PROPHYLAXIS IN PATIENTS WITHOUT PRIOR SBP OR GI
  HEMORRHAGE?

Garcia-Tsao, Can J Gastroenterol. 2004
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SBP-Prophylaxis

• 1-SHORT-TERM PRIMARY PROPHYLAXIS
• A meta-analysis of five randomized controlled
  trials shows that short-term antibiotic
  prophylaxis not only resulted in a significant
  decrease in the incidence of infections (45 in
  controls vs. 14 in antibiotic-treated patients),
  including SBP (27 vs 8) but was also associated
  with a significant improvement in survival (from
  24 in controls to 15 in treated patients).
• The preferred antibiotic is norfloxacin 400 mg
  twice a day orally for 7-day.
• (Bernard Hepatology
  1999 Garcia-Tsao, Can J Gastroenterol. 2004 )

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SBP-Prophylaxis

• 2-LONG-TERM SECONDARY PROPHYLAXIS
• In patients with previous episodes of SBP,
  long-term prophylaxis with oral norfloxacin 400
  mg daily is initiated as soon as the course of
  antibiotics for the acute episode of SBP is
  completed and should be continued until
  disappearance of ascites, death or
  transplantation.
• There is a concern that long-term Prophylaxis
  will lead to emergence of resistant bacteria
• 
  (Rimola et al., J Hepatol 2000
• Garcia-
  Tsao Gastroenterology 2001).

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SBP-Prophylaxis

• 3- PROPHYLAXIS IN PATIENTS WITHOUT PRIOR SBP OR
  GI HEMORRHAGE.
• Currently, there is insufficient data to support
  the use of long-term antibiotic prophylaxis in
  cirrhotic patients with ascites who are not
  bleeding and who have not had a previous episode
  of SBP.
• Patients with an ascites protein gt 1.0 g/dL will
  not develop SBP in a follow-up period of 2 years
  and therefore do not require prophylaxis
• 
  (Garcia- Tsao Gastroenterology 2001).

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SBP-Prophylaxis

• In patients with low ascites protein levels who
  have never had SBP or who are not hospitalized
  with GI hemorrhage, efforts should be made to
  identify other risk factors for SBP.
• In a recent study, a bilirubin gt3.2 mg/dL and a
  platelet count lt98,000 have been able to identify
  up to 55 of patients that will develop SBP.
• Results of prophylactic, placebo-controlled
  trials in this group of patients will confirm
  that these are in fact high risk patients and,
  more importantly, evaluate the efficacy of
  primary prophylaxis.
• (Grange J
  Hepatol 1998 Garcia-Tsao, Can J Gastroenterol.
  2004)

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SBP-Prophylaxis

• Vaccination of all cirrhotic patients with
  polyvalent pneumococcal vaccine is established as
  effective in reducing colonization in cirrhosis.
• In cirrhotic patients, same-day treatment centers
  should be used instead of hospitalization if
  hospitalization is necessary, intensive care
  units and hospital days should be used in a
  miserly manner.
• 
  (Zetterman, Semin Liver Dis
  1995
• 
  Chang et al., Infect Control
  Hosp Epidemiol 1998)

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• In hospitals, skin cleanliness and universal
  precautions to diminish patient-to-patient
  colonization must be observed.
• Urinary and intravenous catheters should be
  avoided whenever possible, and proven techniques
  should be used to minimize infection when these
  are necessary.
• (Iber,
  American J Gastro 1999))

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• Thank You

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Bacterial infections in liver cirrhosis

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Bacterial infections is second in frequency to
bleeding varices as a fatal complication of
cirrhosis. Prospective series describe an
incidence of infections in hospitalized patients
of 15, 20 and 47. A recently published series
reported the presence of bacterial infections
(either at the time of admission or during
hospitalization) in 32 of cirrhotic patients.
These figures are in contrast with the
hospital-cquired infection rate in the general
hospital population reported to be between 5 and
7.
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• Studies in the 1980s showed that the most common
  infections were urinary tract infections,
  spontaneous bacterial peritonitis (SBP) and
  pneumonia, and also showed that approximately
  70-80 of infecting organisms were gram-negative
  bacilli (GNB). In a recent large series SBP was
  the most common infection, followed by urinary
  tract infection, pneumonia and bacteremia. The
  causative organisms isolated in SBP and urinary
  tract infections were mainly GNB. In contrast,
  the most frequent bacteria isolated in pneumonia
  and bacteremias associated with invasive
  procedures were gram-positive cocci.

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