Spontaneous Bacterial Peritonitis - Pathogenesis , Clinical Features & Management

SPONTANEOUS
BACTERIAL
PERITONITIS

Bacterial infections
● a common complication in patients with cirrhosis
● associated with the development of other cirrhosis-related complications (e.g.,
AKI, hepatic encephalopathy)
● poor prognosis.
Patients with cirrhosis are at higher risk of developing bacterial infections ( the risk of
sepsis is 2.6-fold higher in patients with cirrhosis than in patients without underlying
chronic liver disease )
The frequency of bacterial infections in patients with cirrhosis admitted to a hospital
ranges from 25% to 46%.

Spontaneous Bacterial Peritonitis ( SBP )
One of the major complications in patients with cirrhosis and ascites.
DEFINITION : Bacterial infection of the ascitic fluid, without any specific
identifiable intraabdominal treatable source of infection.
Together with urinary tract infections, SBP represents the most common
type of infection in patients with cirrhosis, followed by pneumonia, soft
tissue infections, and spontaneous bacteremia.
The mortality rate of SBP is ~ 20%

Pathogenesis
The increased risk of bacterial infections in patients with cirrhosis is
explained by multiple factors :
● Alterations in the gut-liver axis characterized by gut dysbiosis,
increased intestinal permeability, and bacterial translocation
● The immune dysfunction characteristic of cirrhosis
● Local peritoneal factors
● Genetic factors

Alterations in the gut liver axis
Alterations in gut liver axis in cirrhosis results in pathologic bacterial translocation and
spillover of endotoxins into the systemic circulation, thus facilitating the development of
bacterial infections.
Increased intestinal permeability in patients with cirrhosis may be caused by
● structural changes in the intestinal mucosa (e.g., congestion, edema),
● oxidative stress,
● local inﬂammation.
● Small Intestinal Bacterial Overgrowth ( SIBO )
SIBO is the result, at least in part, of delayed intestinal transit in patients with cirrhosis.
Autonomic dysfunction, increased NO, and oxidative stress have been suggested to play a role in
decreased intestinal motility in these patients.

Cirrhosis associated immune dysfunction
● Impaired immune response occurs in advanced cirrhosis :
increased susceptibility to bacterial infections.
● Impairment in the immune surveillance capacity of the liver
● A decrease in the hepatic synthesis of proteins involved in
innate immunity and pattern recognition, thus causing a
decreased bactericidal capacity of phagocytic cells

● Progression of cirrhosis is also associated with impairment in the
function of circulating immune cells.
● Decompensated cirrhosis is associated with systemic inﬂammation :
persistent activation of circulating immune cells that show increased
markers of activity, and impaired phagocytic capacity.
● As cirrhosis progresses, the immune dysfunction is characterized by
features of immunodeﬁciency, which are thought to be associated with
an increased risk of bacterial infections in patients with more advanced
liver disease and, particularly, in those with acute-on-chronic liver failure
(ACLF).

Local factors
● Although data are conﬂicting, generally a low ascitic ﬂuid protein
concentration (<1.0 to 1.5 g/dL) has been associated with an increase in the
risk of SBP.
● In addition, a few reports suggest that peritoneal macrophages from patients
with cirrhosis and ascites may be functionally impaired, thereby leading to a
decreased capacity for bacterial elimination and, thus, increased
susceptibility to bacterial infections.
● In general, however, information on local factors is limited.

Clinical features
● Heterogeneous clinical presentation
● Asymptomatic / Symptomatic
● Symptomatic : With or without Local symptoms ( abdominal pain / vomiting / loose stools )
Associated features :
(1) signs of systemic inﬂammation (i.e., fever, high leukocyte count, high serum C-reactive
protein level, tachycardia);
(2) deterioration of liver function;
(3) hepatic encephalopathy;
(4) AKI; or
(5) septic shock

A diagnostic paracentesis should be performed to look for SBP in all
patients with cirrhosis and ascites on admission to the hospital and
whenever complications, particularly bleeding, hepatic
encephalopathy, and AKI, develop.
Early diagnosis of SBP is essential for improving outcomes, because a
delay in starting antibiotic treatment is associated with substantially
increased mortality.

Diagnosis
Ascitic neutrophil count > 250/mm3
Ascitic fluid culture
● Should always be performed in blood culture bottles.
● A positive culture is not necessary for the diagnosis of SBP
● If the culture is positive, the ascitic fluid culture is useful for guiding
antibiotic treatment.
● Despite improvements in methods, ascitic fluid cultures may be
negative in up to 60% of patients with SBP.
● Patients with culture-negative SBP should be managed identically to
those with positive culture results.

Bacterascites : A positive ascitic ﬂuid culture result but an ascitic
neutrophil count below 250/ mm3.
In most cases, bacterascites is due to spontaneous bacterial colonization
of ascites
It can be either asymptomatic or associated with symptoms such as
abdominal pain or signs of systemic inﬂammation.
Outcomes : Spontaneous resolution / Development of SBP

Don’t forget about secondary bacterial peritonitis !
Infrequently (approximately 5% of cases of peritonitis), patients with
cirrhosis and ascites may also develop secondary bacterial peritonitis due
to intestinal perforation or another intra abdominal condition.
Patients usually present with abdominal pain, and the ascitic fluid will show
a high neutrophil count, high protein concentration, and multiple organisms
on ascitic fluid culture.
If clinically suspected, CT should be performed to confirm the diagnosis,
and surgery should be considered

Treatment
● Start antibiotics as soon as after a diagnosis of SBP is
made
● Check vital signs regularly
● Monitor liver & kidney function

Antibiotics
Empirical antibiotic treatment should be based on the following:
(1) risk of multidrug resistant (MDR) bacteria;
(2) severity of the infection; and
(3) local epidemiology
MDR bacteria, : bacteria with acquired nonsusceptibility to at least 1 agent in 3 or
more antimicrobial categories

For community-acquired infections, the most common bacteria that cause SBP are
Gram-negative organisms.
The empirical antibiotic treatment of choice for patients with community-acquired SBP
has classically been a third-generation cephalosporin.
Alternative options
● Amoxicillin/clavulanic acid
● Fluoroquinolone
Fluoroquinolones are not recommended in patients who are taking these antibiotics for
prophylaxis of SBP , due to a high rate of ﬂuoroquinolone-resistant bacteria.

The major risk factors for infections caused by MDR organisms :r
● Repeated hospitalizations or repeated contact with the health care environment,
● Noninvasive procedures, and
● Recent antibiotic treatment.
Patients with cirrhosis are at high risk of MDR bacterial infections because they usually
present with these risk factors.
Health care-associated SBP and nosocomial SBP have a higher risk of being caused by
MDR bacteria.
MDR bacteria increase the mortality rate of SBP infection up to 4-fold.

Piperacillin/tazobactam has been recommended as the ﬁrst-line treatment in
patients with health care-associated or nosocomial SBP in areas with a low
prevalence of MDR bacteria.
Severe health care-associated or nosocomial SBP— that is, those who fulﬁll
criteria for sepsis / In areas with a high prevalence of MDR bacteria : the
recommended empirical antibiotic treatment is meropenem alone or in
combination with vancomycin or daptomycin, or linezolid.
The antibiotic regimen should be adjusted according to bacterial susceptibility
based on culture results to avoid the spread of MDR bacteria.

Algorithm for the choice of empirical antibiotic therapy in a patient
with SBP
The selection of empirical antibiotic treatment should be based on
● the setting in which the infection is acquired (community, health
care associated [HCA], or nosocomial),
● the severity of the episode of SBP , and
● whether the patient has sepsis or resides in an area of high
prevalence for multidrug-resistant (MDR) bacteria.
*IV vancomycin should be used in areas with a high prevalence of
methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin
susceptible enterococci.
**Daptomycin or linezolid should be used in areas with a high prevalence of
vancomycin resistant enterococci.

Extensively drug resistant bacteria, : Nonsusceptibility to at least 1
agent in all but 2 or fewer antimicrobial categories, or
Pandrug resistance bacteria : Nonsusceptibility to all agents in all
antimicrobial categories

Prevention of AKI
SBP without septic shock may lead to a further circulatory dysfunction,
thereby increasing the risk of development of HRS.
Guidelines recommend the administration of IV albumin, 1.5 g/kg body
weight at diagnosis and 1 g/kg body weight on day 3, to all patients with
SBP.
( Treatment with albumin was particularly useful in patients with a serum
bilirubin level greater than 4 mg/ dL and serum creatinine level greater
than 1 mg/dL)

Treatment of infections caused by extensively drug resistant or pandrug
resistant bacteria may lead to the use of antibiotics that are known to
have a high risk of nephrotoxicity and that are usually avoided in patients
with cirrhosis and ascites, such as vancomycin, aminoglycosides, or
colistin.
If the use of these antibiotics is mandatory for the management of SBP,
kidney function should be closely monitored in these patients.
In addition, serum levels of vancomycin or aminoglycosides should be
assessed, and antibiotic doses adjusted accordingly.

The efficacy of antibiotic treatment should be monitored by performing
another diagnostic paracentesis 48 hours after the initiation of therapy.
If at this point the ascitic fluid neutrophil count has not decreased by at least
25% from the pretreatment value, there is a high probability of failure to
respond to therapy and, thus, a poor outcome.
If antibiotic treatment is not showing efficacy, it is likely that SBP may be
caused by bacteria resistant to the current antibiotic and that treatment
should be modified according to culture results or empirically to treat MDR
bacteria.

Prophylaxis
The goal of SBP prophylaxis is to decrease the frequency of the
infection in patients at high risk.
Because translocation of Gram negative bacteria from the gut plays a
key role in the pathophysiology of SBP, prophylaxis is aimed at
achieving selective intestinal decontamination by reducing
Gram-negative bacteria.

Although beneﬁcial effects of prophylactic antibiotic therapy
have been described, long-term antibiotic administration may
lead to the emergence of MDR bacteria, and antibiotic
prophylaxis should only be used in high risk-group patients.

A randomized controlled trial showed that primary prophylaxis with
norﬂoxacin, 400 mg/day, in patients with low-protein ascites (<1.5
g/dL) and advanced liver failure (Child-Pugh score ≥9 [see Chapter
92]), serum bilirubin level ≥3 mg/dL) or impaired kidney function
(serum creatinine level ≥1.2 mg/dL or serum sodium <130 mEq/L)
signiﬁcantly reduced
● The one-year probability of developing SBP (from 61% to 7%)
● The one year probability of HRS (from 41% to 28%) and
● Improved the 3-month survival (from 62% to 94%).

Therefore, long-term oral administration of norﬂoxacin, 400 mg/day
(or a suitable alternative antibiotic), is recommended in these
patients.
In patients who experience persistent improvement in cirrhosis and
resolution of ascites, antibiotic prophylaxis can be withdrawn.
For hospitalized patients with GI bleeding, IV ceftriaxone, 1 g/day for
7 days, is recommended.

Patients who recover from an episode of SBP are at a high risk of
recurrent SBP, with a risk of recurrence at one year of approximately 70%.
A randomized, double-blind, placebo-controlled trial showed that
long-term oral administration of norﬂoxacin, 400 mg/day, decreased the
one-year rate of recurrence of SBP from 68% in the placebo group to 20%
in the treated group. Therefore, all patients who have had one episode of
SBP should be treated with norﬂoxacin or another appropriate antibiotic.

Epidemiologic studies have shown that long-term administration of
norfloxacin increases the risk of developing infections caused by MDR
bacteria by 2.7 fold.
Rifaximin has been proposed as a potential alternative prophylactic
treatment. A case-control study described a significant benefit to
rifaximin in the prevention of SBP when used in patients with hepatic
encephalopathy.
Rifaximin could theoretically be effective in preventing the development
of SBP; however, data specifically assessing the efficacy and safety of
rifaximin in primary and secondary prophylaxis of SBP are not available.

Spontaneous Bacterial Peritonitis - Pathogenesis , Clinical Features & Management

Spontaneous Bacterial Peritonitis - Pathogenesis , Clinical Features & Management

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