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Peritonitis and Abdominal

Sepsis
Updated: Jul 23, 2019 | Author: Brian J Daley, MD, MBA, FACS,
FCCP, CNSC; Chief Editor: Praveen K Roy, MD, AGAF more...

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Background
Peritonitis is defined as an inflammation of the serosal
membrane that lines the abdominal cavity and the
organs contained therein. The peritoneum, which is an
otherwise sterile environment, reacts to various
pathologic stimuli with a fairly uniform inflammatory
response. Depending on the underlying pathology, the
resultant peritonitis may be infectious or sterile (ie,
chemical or mechanical). The abdomen is the second
most common source of sepsis and secondary
peritonitis. [1] Intra-abdominal sepsis is an inflammation
of the peritoneum caused by pathogenic
microorganisms and their products. [2] The
inflammatory process may be localized (abscess) or
diffuse in nature. (See Pathophysiology.)

Peritonitis is most often caused by introduction of an

infection into the otherwise sterile peritoneal
environment through organ perforation, but it may also
result from other irritants, such as foreign bodies, bile
from a perforated gall bladder or a lacerated liver, or
gastric acid from a perforated ulcer. Women also
experience localized peritonitis from an infected
fallopian tube or a ruptured ovarian cyst. Patients may
present with an acute or insidious onset of symptoms,
limited and mild disease, or systemic and severe
disease with septic shock. (See Etiology.)

Peritoneal infections are classified as primary (ie, from

hematogenous dissemination, usually in the setting of
an immunocompromised state), secondary (ie, related
to a pathologic process in a visceral organ, such as
perforation or trauma, including iatrogenic trauma), or
tertiary (ie, persistent or recurrent infection after
adequate initial therapy). Primary peritonitis is most
often spontaneous bacterial peritonitis (SBP) seen
mostly inpatients with chronic liver disease. Secondary
peritonitis is by far the most common form of peritonitis
encountered in clinical practice. Tertiary peritonitis
often develops in the absence of the original visceral
organ pathology. (See Presentation.)

Infections of the peritoneum are further divided into

generalized (peritonitis) and localized (intra-abdominal
abscess). This article focuses on the diagnosis and
management of infectious peritonitis and abdominal
abscesses. An abdominal abscess is seen in the image
below.

Peritonitis and abdominal sepsis. A 35-year-old

man with a history of Crohn disease presented
with pain and swelling in the right abdomen. In
figure A, a thickened loop of terminal ileum is
evident adherent to the right anterior abdominal
wall. In figure B, the right anterior abdominal wall
is markedly thickened and edematous, with
adjacent inflamed terminal ileum. In figure C, a
right lower quadrant abdominal wall abscess and
enteric fistula are observed and confirmed by
the presence of enteral contrast in the
abdominal wall.

View Media Gallery

The diagnosis of peritonitis is usually clinical.

Diagnostic peritoneal lavage may be helpful in patients
who do not have conclusive signs on physical
examination or who cannot provide an adequate
history; in addition, paracentesis should be performed
in all patients who do not have an indwelling peritoneal
catheter and are suspected of having SBP, because
results of aerobic and anaerobic bacterial cultures,
used in conjunction with the cell count, are useful in
guiding therapy. (See Workup.)

The management approach to peritonitis and

peritoneal abscesses targets correction of the
underlying process, administration of systemic
antibiotics, and supportive therapy to prevent or limit
secondary complications due to organ system failure.
(See Treatment and Medication.)

Early control of the septic source is mandatory and can

be achieved operatively and nonoperatively.
Nonoperative interventions include percutaneous
abscess drainage, as well as percutaneous and
endoscopic stent placements. Operative management
addresses the need to control the infectious source
and to purge bacteria and toxins. The type and extent
of surgery depends on the underlying disease process
and the severity of intra-abdominal infection.

For patient education resources, Digestive Disorders

Center as well as Abdominal Pain
(Adults), Appendicitis, Diverticulitis
(Diverticulosis), Cirrhosis, and Sepsis.

Anatomy
The peritoneum is the largest and most complex
serous membrane in the body. It forms a closed sac (ie,
coelom) by lining the interior surfaces of the abdominal
wall (anterior and lateral), by forming the boundary to
the retroperitoneum (posterior), by covering the
extraperitoneal structures in the pelvis (inferior), and by
covering the undersurface of the diaphragm (superior).
This parietal layer of the peritoneum reflects onto the
abdominal visceral organs to form the visceral
peritoneum. It thereby creates a potential space
between the two layers (ie, the peritoneal cavity).

The peritoneum consists of a single layer of flattened

mesothelial cells over loose areolar tissue. The loose
connective tissue layer contains a rich network of
vascular and lymphatic capillaries, nerve endings, and
immune-competent cells, particularly lymphocytes and
macrophages. The peritoneal surface cells are joined
by junctional complexes, thus forming a dialyzing
membrane that allows passage of fluid and certain
small solutes. Pinocytotic activity of the mesothelial
cells and phagocytosis by macrophages allow for the
clearance of macromolecules.

Normally, the amount of peritoneal fluid present is less

than 50 mL, and only small volumes are transferred
across the considerable surface area in a steady state
each day. The peritoneal fluid represents a plasma
ultrafiltrate, with electrolyte and solute concentrations
similar to that of neighboring interstitial spaces and a
protein content of less than 30 g/L, mainly albumin. In
addition, peritoneal fluid contains small numbers of
desquamated mesothelial cells and various numbers
and morphologies of migrating immune cells
(reference range is < 300 cells/μ L, predominantly of
mononuclear morphology).

The peritoneal cavity is divided incompletely into

compartments by the mesenteric attachments and
secondary retroperitonealization of certain visceral
organs. A large peritoneal fold, the greater omentum,
extends from the greater curvature of the stomach and
the inferior aspect of the proximal duodenum
downward over a variable distance to fold upon itself
(with fusion of the adjacent layers) and ascends back
to the taenia omentalis of the transverse colon. This
peritoneal fold demonstrates a slightly different
microscopic anatomy, with fenestrated surface
epithelium and a large number of adipocytes,
lymphocytes, and macrophages, and it functions as a
fat storage location and a mobile immune organ.

The compartmentalization of the peritoneal cavity, in

conjunction with the greater omentum, influences the
localization and spread of peritoneal inflammation and
infections.

Pathophysiology
In peritonitis caused by bacteria, the physiologic
response is determined by several factors, including
the virulence of the contaminant, the size of the
inoculum, the immune status and overall health of the
host (eg, as indicated by the Acute Physiology and
Chronic Health Evaluation II [APACHE II] score), and
elements of the local environment, such as necrotic
tissue, blood, or bile. [3]

Intra-abdominal sepsis from a perforated viscus (ie,

secondary peritonitis or suppurative peritonitis) results
from direct spillage of luminal contents into the
peritoneum (eg, perforated peptic ulcer, diverticulitis,
appendicitis, iatrogenic perforation). With the spillage
of the contents, gram-negative and anaerobic bacteria,
including common gut flora, such as Escherichia coli
and Klebsiella pneumoniae, enter the peritoneal cavity.
Endotoxins produced by gram-negative bacteria lead
to the release of cytokines that induce cellular and
humoral cascades, resulting in cellular damage, septic
shock, and multiple organ dysfunction syndrome
(MODS).

The mechanism for bacterial inoculation of ascites has

been the subject of much debate since Harold Conn
first recognized it in the 1960s. Enteric organisms have
traditionally been isolated from more than 90% of
infected ascites fluid in spontaneous bacterial
peritonitis (SBP), suggesting that the gastrointestinal
(GI) tract is the source of bacterial contamination. The
preponderance of enteric organisms, in combination
with the presence of endotoxin in ascitic fluid and
blood, once favored the argument that SBP was due to
direct transmural migration of bacteria from an
intestinal or hollow organ lumen, a phenomenon called
bacterial translocation. However, experimental
evidence suggests that direct transmural migration of
microorganisms might not be the cause of SBP.

An alternative proposed mechanism for bacterial

inoculation of ascites suggests a hematogenous
source of the infecting organism in combination with
an impaired immune defense system. Nonetheless, the
exact mechanism of bacterial displacement from the GI
tract into ascites fluid remains the source of much
debate.

A host of factors contributes to the formation of

peritoneal inflammation and bacterial growth in the
ascitic fluid. A key predisposing factor may be the
intestinal bacterial overgrowth found in people with
cirrhosis, mainly attributed to decreased intestinal
transit time. Intestinal bacterial overgrowth, along with
impaired phagocytic function, low serum and ascites
complement levels, and decreased activity of the
reticuloendothelial system, contributes to an increased
number of microorganisms and decreased capacity to
clear them from the bloodstream, resulting in their
migration into and eventual proliferation within ascites
fluid.

Interestingly, adults with SBP typically have ascites, but

most children with SBP do not have ascites. The
reason for and mechanism behind this is the source of
ongoing investigation.

Fibrinolysis
Alterations in fibrinolysis (through increased
plasminogen activator inhibitor activity) and the
production of fibrin exudates have an important role in
peritonitis. The production of fibrin exudates is an
important part of the host defense, but large numbers
of bacteria may be sequestered within the fibrin matrix.
This may retard systemic dissemination of
intraperitoneal infection and may decrease early
mortality rates from sepsis, but it also is integral to the
development of residual infection and abscess
formation. As the fibrin matrix matures, the bacteria
within are protected from host clearance mechanisms.

Whether fibrin ultimately results in containment or

persistent infection may depend on the degree of
peritoneal bacterial contamination. In animal studies of
mixed bacterial peritonitis that examined the effects of
systemic defibrinogenation and those of abdominal
fibrin therapy, heavy peritoneal contamination
uniformly led to severe peritonitis with early death (<
48 h) because of overwhelming sepsis.

Bacterial load
Bacterial load and the nature of the pathogen also play
important roles. Some studies suggest that the number
of bacteria present at the onset of abdominal
infections is much higher than originally believed
(approximately 2 × 108 colony forming unit [CFU]/mL,
much higher than the 5 × 105 CFU/mL inocula routinely
used for in vitro susceptibility testing). This bacterial
load may overwhelm the local host defense.

Bacterial virulence
Bacterial virulence factors [4] that interfere with
phagocytosis and with neutrophil-mediated bacterial
killing mediate the persistence of infections and
abscess formation. Among these virulence factors are
capsule formation, facultative anaerobic growth,
adhesion capabilities, and succinic acid production.
Synergy between certain bacterial and fungal
organisms may also play an important role in impairing
the host's defense. One such synergy may exist
between Bacteroides fragilis and gram-negative
bacteria, particularly E coli (see the image below) ,
where co-inoculation significantly increases bacterial
proliferation and abscess formation.

Peritonitis and abdominal sepsis. Gram-negative

Escherichia coli.

View Media Gallery

Enterococci
Enterococci may be important in enhancing the
severity and persistence of peritoneal infections. In
animal models of peritonitis with E coli and B fragilis,
the systemic manifestations of the peritoneal infection
and bacteremia rates were increased, as were
bacterial concentrations in the peritoneal fluid and rate
of abscess formation. Nevertheless, the role of
Enterococcus organisms in uncomplicated intra-
abdominal infections remains unclear. Antibiotics that
lack specific activity against Enterococcus are often
used successfully in the therapy of peritonitis, and the
organism is not often recovered as a blood-borne
pathogen in intra-abdominal sepsis.

Fungi
The role of fungi in the formation of intra-abdominal
abscesses is not fully understood. Some authors
suggest that bacteria and fungi exist as nonsynergistic
parallel infections with incomplete competition,
allowing the survival of all organisms. In this setting,
treatment of the bacterial infection alone may lead to
an overgrowth of fungi, which may contribute to
increased morbidity.

Abscess formation
Abscess formation occurs when the host defense is
unable to eliminate the infecting agent and attempts to
control the spread of this agent by
compartmentalization. This process is aided by a
combination of factors that share a common feature, ie,
impairment of phagocytotic killing. Most animal and
human studies suggest that abscess formation occurs
only in the presence of abscess-potentiating agents.
Although the nature and spectrum of these factors
have not been studied exhaustively, certain fiber
analogues (eg, bran) and the contents of autoclaved
stool have been identified as abscess-potentiating
agents. In animal models, these factors inhibit
opsonization and phagocytotic killing by interference
with complement activation.

Cytokines
The role of cytokines in the mediation of the body's
immune response and their role in the development of
the systemic inflammatory response syndrome (SIRS)
and multiple organ failure (MOF) have been a major
focus of research over the past decade. Comparatively
few data exist about the magnitude of the
intraperitoneal/abscess cytokine response and
implications for the host. Existing data suggest that
bacterial peritonitis is associated with an immense
intraperitoneal compartmentalized cytokine response.
Higher levels of certain cytokines (ie, tumor necrosis
factor-alpha [TNF-alpha], interleukin [IL]-6) have been
associated with worse outcomes, as well as secondary
(uncontrolled) activation of the systemic inflammatory
cascade.

Etiology
The etiology of disease depends on the type, as well
as location, of peritonitis, as follows:

Primary peritonitis

Secondary peritonitis

Tertiary peritonitis

Chemical peritonitis

Peritoneal abscess

Primary peritonitis
Spontaneous bacterial peritonitis (SBP) is an acute
bacterial infection of ascitic fluid. Contamination of the
peritoneal cavity is thought to result from translocation
of bacteria across the gut wall or mesenteric
lymphatics and, less frequently, via hematogenous
seeding in the presence of bacteremia.

SBP can occur as a complication of any disease state

that produces the clinical syndrome of ascites, such as
heart failure and Budd-Chiari syndrome. Children with
nephrosis or systemic lupus erythematosus who have
ascites have a high risk of developing SBP. The highest
risk of SBP, however is in patients with cirrhosis who
are in a decompensated state. [5] In particular,
decreased hepatic synthetic function with associated
low total protein level, low complement levels, or
prolonged prothrombin time (PT) is associated with
maximum risk. Patients with low protein levels in ascitic
fluid (< 1 g/dL) have a 10-fold higher risk of developing
SBP than those with a protein level greater than 1 g/dL.
Approximately 10-30% of patients with cirrhosis and
ascites develop SBP. [6] The incidence rises to more
than 40% with ascitic fluid protein contents of less than
1 g/dL (which occurs 15% of patients), presumably
because of decreased ascitic fluid opsonic activity.

More than 90% of cases of SBP are caused by a

monomicrobial infection. The most common pathogens
include gram-negative organisms (eg, E coli [40%], K
pneumoniae [7%], Pseudomonas species, Proteus
species, other gram-negative species [20%]) and gram-
positive organisms (eg, Streptococcus pneumoniae
[15%], other Streptococcus species [15%], and
Staphylococcus species [3%]) (see Table 1). However,
some data suggest that the percentage of gram-
positive infections may be increasing. [7, 8] One study
cites a 34.2% incidence of streptococci, ranking in
second position after Enterobacteriaceae. [8] Viridans
group streptococci (VBS) accounted for 73.8% of these
streptococcal isolates. A single organism is noted in
92% of cases, and 8% of cases are polymicrobial.

Anaerobic microorganisms are found in less than 5% of

cases, and multiple isolates are found in less than 10%.

Secondary peritonitis
Worldwide, secondary peritonitis accounts for about 1%
of urgent/emergent hospital admissions and is the
second most common cause of sepsis in intensive care
units. [9] Common etiologic entities of secondary
peritonitis (SP) include perforated appendicitis;
perforated gastric or duodenal ulcer; perforated
(sigmoid) colon caused by diverticulitis, volvulus, or
cancer; and strangulation of the small bowel (see Table
1). Necrotizing pancreatitis can also be associated with
peritonitis in the case of infection of the necrotic tissue.

The pathogens involved in SP differ in the proximal

and distal gastrointestinal (GI) tract. Gram-positive
organisms predominate in the upper GI tract, with a
shift toward gram-negative organisms in the upper GI
tract in patients on long-term gastric acid suppressive
therapy. Contamination from a distal small bowel or
colon source initially may result in the release of
several hundred bacterial species (and fungi); host
defenses quickly eliminate most of these organisms.
The resulting peritonitis is almost always polymicrobial,
containing a mixture of aerobic and anaerobic bacteria
with a predominance of gram-negative organisms (see
Table 1).

As many as 15% of patients who have cirrhosis with

ascites who were initially presumed to have SBP have
SP. In many of these patients, clinical signs and
symptoms alone are not sensitive or specific enough
to reliably differentiate between the 2 entities. A
thorough history, evaluation of the peritoneal fluid, and
additional diagnostic tests are needed to do so; a high
index of suspicion is required.

Table 1. Common Causes of Secondary Peritonitis

(Open Table in a new window)

Source
Causes
Regions

Boerhaave syndrome

Malignancy
Esophagus
Trauma (mostly penetrating)

Iatrogenic*

Peptic ulcer perforation

Malignancy (eg,
adenocarcinoma, lymphoma,
Stomach gastrointestinal stromal tumor)

Trauma (mostly penetrating)

Iatrogenic*

Peptic ulcer perforation

Duodenum Trauma (blunt and penetrating)

Iatrogenic*

Cholecystitis

Stone perforation from

gallbladder (ie, gallstone ileus)
or common duct

Biliary tract Malignancy

Choledochal cyst (rare)

Trauma (mostly penetrating)

Iatrogenic*

Pancreatitis (eg, alcohol, drugs,

gallstones)
Pancreas
Trauma (blunt and penetrating)

Iatrogenic*

Ischemic bowel

Incarcerated hernia (internal

and external)

Closed loop obstruction

Small
bowel Crohn disease

Malignancy (rare)

Meckel diverticulum

Trauma (mostly penetrating)

Ischemic bowel

Diverticulitis

Malignancy

Large Ulcerative colitis and Crohn

bowel and disease
appendix Appendicitis

Colonic volvulus

Trauma (mostly penetrating)

Iatrogenic

Pelvic inflammatory disease (eg,

Uterus, salpingo-oophoritis, tubo-
salpinx, ovarian abscess, ovarian cyst)
and
Malignancy (rare)
ovaries
Trauma (uncommon)

*Iatrogenic trauma to the upper GI tract,

including the pancreas and biliary tract and
colon, often results from endoscopic
procedures; anastomotic dehiscence and
inadvertent bowel injury (eg, mechanical,
thermal) are common causes of leak in the
postoperative period.

Common organisms cultured in secondary peritonitis

are presented in Table 2, below. [10]

Table 2. Microbial Flora of Secondary Peritonitis (Open

Table in a new window)

Type Organism Percentage

Aerobic

Gram
Escherichia coli 60%
negative

Enterobacter/Klebsiella 26%

Proteus 22%

Pseudomonas 8%

Gram
Streptococci 28%
positive

Enterococci 17%

Staphylococci 7%

Anaerobic Bacteroides 72%

Eubacteria 24%

Clostridia 17%

Peptostreptococci 14%

Peptococci 11%

Fungi Candida 2%

Other rare, nonsurgical causes of intra-abdominal

sepsis include the following:

Chlamydia peritonitis

Tuberculosis peritonitis

Acquired immunodeficiency syndrome (AIDS)-

associated peritonitis

The most common cause of postoperative peritonitis is

anastomotic leak, with symptoms generally appearing
around postoperative days 5-7. After elective
abdominal operations for noninfectious etiologies, the
incidence of SP (caused by anastomotic disruption,
breakdown of enterotomy closures, or inadvertent
bowel injury) should be less than 2%. Operations for
inflammatory disease (ie, appendicitis, diverticulitis,
cholecystitis) without perforation carry a risk of less
than 10% for the development of SP and peritoneal
abscess. This risk may rise to greater than 50% in
gangrenous bowel disease and visceral perforation.

After operations for penetrating abdominal trauma, SP

and abscess formation are observed in a small number
of patients. Duodenal and pancreatic involvement, as
well as colon perforation, gross peritoneal
contamination, perioperative shock, and massive
transfusion, are factors that increase the risk of
infection in these cases.

Peritonitis is also a frequent complication and

significant limitation of peritoneal dialysis. [4] Peritonitis
leads to increased hospitalization and mortality rates.

Tertiary peritonitis
Tertiary peritonitis (see Table 3, below) develops more
frequently in immunocompromised patients and in
persons with significant preexisting comorbid
conditions. Although rarely observed in uncomplicated
peritoneal infections, the incidence of tertiary
peritonitis in patients requiring ICU admission for
severe abdominal infections may be as high as 50-
74%.

Tuberculous peritonitis (TP) is rare in the United States

(< 2% of all causes of peritonitis), but it continues to be
a significant problem in developing countries and
among patients with human immunodeficiency virus
(HIV) infection. The presenting symptoms are often
nonspecific and insidious in onset (eg, low-grade fever,
anorexia, weight loss). Many patients with TP have
underlying cirrhosis. More than 95% of patients with TP
have evidence of ascites on imaging studies, and more
than half of these patients have clinically apparent
ascites.

In most cases, chest radiographic findings in patients

with TP peritonitis are abnormal; active pulmonary
disease is uncommon (< 30%). Results on Gram stain of
ascitic fluid are rarely positive, and culture results may
be falsely negative in up to 80% of patients. A
peritoneal fluid protein level greater than 2.5 g/dL, a
lactate dehydrogenase (LDH) level greater than 90
U/mL, or a predominantly mononuclear cell count of
greater than 500 cells/μ L should raise suspicion of TP
but have limited specificity for the diagnosis.
Laparoscopy and visualization of granulomas on
peritoneal biopsy specimens, as well as cultures
(requires 4-6 wk), may be needed for the definitive