Spontaneous bacterial peritonitis in adults: Pathogenesis, clinical features, and diagnosis

INTRODUCTION — 

Spontaneous bacterial peritonitis (SBP) is an ascitic fluid infection that occurs in the absence of an obvious source of infection (eg, perforated viscus, urinary tract infection, peritoneal dialysis catheter). SBP primarily occurs in patients with cirrhosis and ascites and is usually due to translocation of bacteria from the intestinal lumen. Patients may present with signs and symptoms, such as abdominal pain, fever, or altered mental status. However, some patients with SBP are asymptomatic and are diagnosed when they undergo paracentesis for another reason (eg, hospital admission).

This topic will review the risk factors, clinical features, and diagnosis of SBP. Management of SBP is discussed separately. (See "Spontaneous bacterial peritonitis in adults: Management".)

The evaluation of patients with ascites is discussed separately. (See "Evaluation of adults with ascites".)

Diagnosis and management of fungal peritonitis are discussed separately. (See "Candida infections of the abdomen and thorax".)

PATHOGENESIS

Microbiology and bacterial overgrowth — Most cases of SBP are caused by enteric bacteria (mainly Escherichia coli, Klebsiella pneumonia, Enterococcus faecalis, and Enterococcus faecium) [1-3]. Studies suggested that E. coli was isolated in more than 50 percent of patients with SBP and positive ascitic fluid culture, whereas K. pneumonia was the second most common pathogen [4-8]. Over time, reports of infection with Gram-positive bacteria such as Enterococcus and Staphylococcus have been increasing [9,10].

Multidrug-resistant (MDR) Gram-negative pathogens are increasingly prevalent causes of SBP, especially in regions with high rates of these pathogens [3]. Patients with cirrhosis often have risk factors for colonization with MDR bacteria due to frequent health care and antibiotic exposure [1].

Overgrowth and dysbiosis (alteration of the microbial population) likely play a role in the development of SBP [2,11]. Patients with cirrhosis have delayed intestinal transit and impaired small bowel motility, which may allow pathogens more time to replicate, leading to small intestinal bacterial overgrowth [11].

Bacterial entry into ascitic fluid — Most cases of SBP are due to translocation of bacteria through the intestinal wall. Bacterial translocation is the passage of bacteria from the intestinal lumen through the intestinal wall and into the bloodstream, lymphatics, and other extraintestinal sites, including the mesenteric lymph nodes [11].

Bacteria are felt to penetrate the intestinal lumen due to impaired permeability of the intestinal mucosal barrier seen in patients with cirrhosis. The bacteria themselves may play a role, as organisms isolated from patients with SBP have been shown to disrupt cell junctions, and microbial dysbiosis has been reported to affect gut barrier function [2,12].

Once bacteria enter the extraintestinal space, high flow and pressure associated with portal hypertension may cause lymphatics carrying contaminated lymph to rupture into the ascitic fluid. Alternatively, mesenteric lymphatics may carry organisms into the systemic circulation, which can lead to SBP.

Bacterial entry into ascitic fluid may occur prior to the development of clinical SBP [13,14]. Patients with cirrhosis and ascites can have bacterial DNA and toxins in their serum and ascitic fluid even when viable organisms cannot be cultured [11,12]. Low levels of translocation of intact bacteria or pieces of bacteria may lead to activation of tumor necrosis factor (TNF), which may explain the higher levels of TNF that have been observed in patients who ultimately develop SBP compared with controls [15]. The presence of bacterial DNA in serum and ascitic fluid is a risk factor for mortality in patients with cirrhosis [16].

Severity of liver disease has been associated with risk of bacterial translocation. In a study including 79 patients with cirrhosis who underwent sampling of mesenteric lymph nodes, the prevalence of enteric organism growth from lymph node culture increased with progression of Child-Pugh score (3, 8, and 31 percent positive culture rates for patients with Child-Pugh class A, B, and C, respectively) [17].

Proton pump inhibitors (PPIs) may increase the risk of bacterial translocation and subsequent SBP [18,19]. By decreasing gastric acid production, PPIs provide a more hospitable environment for microbial survival in the stomach and proximal small intestine [20]. PPIs have also been shown to decrease stomach and intestinal motility and decrease phagocyte oxidative burst, which could further weaken defenses against resident bacteria [20,21].

Host defenses — When a bacterial organism enters ascitic fluid, the risk of SBP is influenced by the bacterial virulence and the host's resistance to infection.

In the peritoneal cavity, resident macrophages represent the first line of defense [22]. If these phagocytes fail to eradicate the colonizing microbes, complement is activated and cytokines are released. Neutrophils (also referred to as polymorphonuclear neutrophils) enter the peritoneum to seek and destroy invading organisms. If complement levels are inadequate or the neutrophils are dysfunctional, then colonization may not be contained and a potentially serious infection may develop.

Cirrhosis is a form of acquired immune deficiency, creating an environment that facilitates peritoneal infection [23,24]. The function of both motile (eg, neutrophils) and stationary (eg, Kupffer cells) phagocytes is reduced in patients with cirrhosis, as are opsonin levels (proteins that mark pathogens for destruction by phagocytes) [25-27]. Furthermore, serum complement deficiency is common in patients with decompensated cirrhosis, and complement levels in ascitic fluid are frequently five- to ten-fold lower than serum levels. In fact, ascitic fluid complement concentrations may be similar to those of the serum of patients with congenital complement deficiency. (See "Overview and clinical assessment of the complement system".)

RISK FACTORS — 

For patients with cirrhosis, risk factors for SBP include the following [28]:

●Severity of cirrhosis (eg, Child-Pugh score ≥9 points, total serum bilirubin ≥3 mg/dL [51 micromol/L]) (calculator 1 and calculator 2)

●Ascitic fluid total protein concentration <1 g/dL (10 g/L)

●Prior episode of SBP

●Upper gastrointestinal bleeding

●Malnutrition (see "Nutritional issues in adult patients with cirrhosis", section on 'Nutrition assessment')

Emerging data suggest that PPIs are a risk factor for SBP [18,20,29-31]. In a database study including over 350,000 patients with cirrhosis, use of PPIs was associated with a higher risk of SBP compared with no PPI use (odds ratio [OR] 2.31, 95% CI 2.21-2.42) [31]. These findings support evaluating the indications for and risk of using such medications in patients with cirrhosis. (See "Overview of medication adjustments for adult patients with cirrhosis", section on 'Acid reducers'.)

CLINICAL FEATURES

Patient presentation

Symptomatic patients — For some patients, the symptoms and signs of SBP may be subtle because ascitic fluid separates the visceral peritoneum from the parietal peritoneum.

Common findings include abdominal pain, abdominal tenderness on palpation, fever, and altered mental status [32]. Less commonly, patients may report diarrhea. The presence of ileus, hypotension, and hypothermia may indicate more severe infection and increased risk of mortality. (See "Spontaneous bacterial peritonitis in adults: Management", section on 'Prognosis'.)

Characteristics of specific symptoms include:

●Abdominal pain and tenderness – Diffuse and continuous abdominal pain is the hallmark of peritonitis. However, abdominal pain, when present, is usually milder in SBP compared with other causes of peritonitis (eg, perforated viscus). (See 'Distinguishing SBP from secondary bacterial peritonitis' below.)

On palpation of the abdomen, muscular rigidity or guarding is not consistent with SBP, although rebound tenderness may be present in some patients. (See "Evaluation of the adult with abdominal pain".)

●Fever – At baseline, most patients with decompensated cirrhosis are mildly hypothermic. Thus, a temperature of ≥37.8 degrees C (≥100 degrees F) raises suspicion for infection.

●Altered mental status – Altered mental status occurs in approximately one-half of patients with SBP [33,34].  Some patients may present with delirium, confusion, or cognitive impairment, whereas other patients may have more subtle alterations in mental status.  

Both the infection itself and hepatic encephalopathy related to decompensated cirrhosis may contribute to changes in mental status. (See "Hepatic encephalopathy in adults: Clinical manifestations and diagnosis".)

Asymptomatic patients — Up to one-third of patients with SBP have no symptoms or signs of infection [35].

Evaluation for SBP in patients without specific symptoms or signs of an abdominal infection may be prompted by another condition such as hospitalization for acute gastrointestinal bleeding or kidney injury. (See 'When to suspect SBP' below.)

Laboratory findings — Laboratory findings in patients with SBP may include peripheral leukocytosis, metabolic acidosis, and/or azotemia. Occasionally, laboratory abnormalities are the only signs of infection.  

DIAGNOSIS

When to suspect SBP — SBP should be suspected in patients with cirrhosis-related ascites and any of the following [36]:

●Symptoms and signs of SBP such as abdominal pain, fever, altered mental status, abdominal tenderness, hypotension, or hypothermia.

●A condition requiring nonelective or emergency hospitalization (eg, acute gastrointestinal bleeding, acute kidney injury, new onset hyponatremia).

●Laboratory abnormalities such as peripheral leukocytosis, metabolic acidosis, or azotemia.

Establishing the diagnosis — The diagnosis of SBP is established by an ascitic fluid absolute neutrophil count ≥250 cells/microL [37]. We obtain ascitic fluid cultures to inform antimicrobial therapy. However, we begin antimicrobial therapy for all patients with an ascitic neutrophil count ≥250 cells/microL while awaiting the results of the ascitic fluid culture. (See "Spontaneous bacterial peritonitis in adults: Management", section on 'Antimicrobial therapy'.)

For diagnostic evaluation, at least 40 mL of ascitic fluid should be obtained and sent for the following tests (table 1) (see 'Ascitic fluid (paracentesis)' below):

●White blood cell count with differential. (See 'Cell count with differential' below.)

●Microbiologic tests including Gram stain and culture. (See 'Microbiologic tests' below.)

●Albumin and total protein. Additional tests (eg, glucose, lactate dehydrogenase, amylase, bilirubin) can help to evaluate persistent infection or differentiate SBP from secondary bacterial peritonitis. (See 'Chemistries' below and 'Distinguishing SBP from secondary bacterial peritonitis' below.)

Initial testing

Ascitic fluid (paracentesis) — Obtaining ascitic fluid promptly for laboratory testing is the cornerstone of the evaluation of patients with suspected SBP (table 1). As stated above, an elevated ascitic fluid absolute neutrophil count (≥250 cells/microL) establishes the diagnosis of SBP [32,38]. (See 'Establishing the diagnosis' above.)

Ascitic fluid is obtained via abdominal paracentesis, a bedside procedure in which a needle is inserted into the peritoneal cavity and ascitic fluid is removed. (See "Diagnostic and therapeutic abdominal paracentesis".)

Timing and safety — If SBP is suspected, paracentesis with analysis of the ascitic fluid should be performed without delay. (See 'When to suspect SBP' above.)

Unless the patient is hemodynamically unstable, the procedure should be performed prior to the administration of antibiotics to optimize culture results.

Delaying or not performing paracentesis has been associated with an increased risk of mortality [39,40]. In a database study of over 17,000 patients with cirrhosis and ascites who were admitted to the hospital with a primary diagnosis of ascites or encephalopathy, paracentesis was performed in 61 percent of patients [39]. Paracentesis was associated with a lower in-hospital mortality rate compared with no paracentesis (6.5 versus 8.5 percent; adjusted odds ratio 0.55, 95% CI 0.41-0.74). In a study of 239 hospitalized patients with SBP, paracentesis within 12 hours of admission was associated with lower mortality rates compared with paracentesis at 12 to 72 hours after hospitalization (13 versus 27 percent) [40].  

Paracentesis may be performed safely in most patients with cirrhosis who have abnormal coagulation studies or thrombocytopenia [41]. Contraindications, technical aspects, and adverse events related to diagnostic paracentesis are discussed separately. (See "Diagnostic and therapeutic abdominal paracentesis", section on 'Indications, contraindications, and special considerations' and "Hemostatic abnormalities in patients with liver disease".)

Cell count with differential — Patients with SBP have an ascitic fluid absolute neutrophil count ≥250 cells/microL. (See 'Establishing the diagnosis' above.)

●Procedure – To obtain cell count with differential, we inject approximately 1 mL of ascitic fluid into a tube containing an anticoagulant solution. The cell count cannot be measured accurately if the fluid clots or is submitted in a non-anticoagulated tube. We ask the laboratory to expedite the cell count and differential to facilitate a timely diagnosis.

The ascitic fluid cell count with differential should be available within a few hours following paracentesis. (See "Spontaneous bacterial peritonitis in adults: Management".)

●Calculating the absolute neutrophil count – The absolute neutrophil count in the ascitic fluid is calculated by multiplying the total white blood cell count (or total "nucleated cell" count) by the percentage of neutrophils in the differential. If the laboratory provides an "expanded differential," including bands or even earlier forms of neutrophils, these should be added to the neutrophil count.

In most laboratories, cell counts and differentials are automated using flow cytometry [42-45]. Automated cell counters have achieved a sensitivity and specificity of close to 100 percent [44]. In addition, they may provide more rapid results than manual cell counts.

●Interpreting bloody ascites – Bloody ascites may occur as a result of traumatic paracentesis. Blood in ascitic fluid can alter neutrophil counts by including neutrophils that enter ascitic fluid from the blood. The absolute ascitic fluid neutrophil count can be corrected by subtracting one neutrophil for every 250 red cells/microL from the ascitic neutrophil count [46].

Interpreting bloody ascites can be complicated based on the timing of the intra-peritoneal bleeding because neutrophils lyse more rapidly than red cells. If the bleeding episode occurred prior to the paracentesis (eg, due to a procedure performed prior to presentation), correction may result in a neutrophil value that is the lower than the actual amount.

Chemistries — We inject several milliliters of fluid into a tube containing no anticoagulant for the following tests:

●Albumin

●Total protein

●Glucose

●Lactate dehydrogenase

●Amylase

●If the fluid is dark orange or brown, we also obtain bilirubin concentration.

Although ascitic fluid chemistry tests are not necessary to confirm the diagnosis of SBP, they can help support the diagnosis in selected cases, particularly if there is also concern for secondary bacterial peritonitis. (See 'Distinguishing SBP from secondary bacterial peritonitis' below.)

Specific findings in patients with SBP include the following:

●Serum-ascites albumin gradient – The serum-ascites albumin gradient indirectly measures portal pressure [47,48]. Because most patients with SBP have decompensated cirrhosis with portal hypertension, an elevated gradient can support the diagnosis of SBP by identifying portal hypertension (with the exception of patients with nephrotic syndrome) [49].

A serum albumin concentration must be obtained on the same day as the ascitic fluid. The ascitic fluid value is subtracted from the serum value to obtain the gradient (table 2) [48]:

•If the difference is ≥1.1 g/dL, the patient likely has portal hypertension.

•If the difference is <1.1 g/dL, the patient is unlikely to have portal hypertension, making SBP less likely.

●Ascitic fluid glucose – In patients with SBP, the glucose concentration generally remains above 50 mg/dL (2.8 mmol/L).

●Ascitic fluid lactate dehydrogenase (LDH) – LDH in ascitic fluid is increased in SBP because LDH is released from neutrophils that have lysed [50]. In one study comparing ascitic fluid LDH levels during SBP infection with baseline values in 22 patients with cirrhosis, the mean ascitic fluid LDH was higher during SBP (183 versus 43 units/L) [50]. However, the upper limit of normal for LDH varies by laboratory.

●Ascitic fluid amylase – The concentration of ascitic fluid amylase is not typically elevated in SBP. Elevated amylase concentration suggests pancreatitis or bowel perforation because a perforated intestine generally leaks amylase into ascitic fluid.

●Ascitic fluid bilirubin – Ascitic fluid bilirubin concentration is generally low in SBP (approximately one-third of normal serum value) [51]. An elevated bilirubin concentration in the ascitic fluid suggests gallbladder or bowel perforation.  

Microbiologic tests — We send ascitic fluid for microbiologic analysis including Gram stain and culture (ie, aerobic and anaerobic) [52]:

●Gram stain – For Gram stain, we send a few milliliters of ascitic fluid in a sterile urine container or a tube containing no anticoagulant. This method facilitates more rapid results because fluid from the blood culture bottles cannot be used for Gram stain until they have incubated for 12 to 24 hours.

Gram stain is often insensitive for detecting SBP and has also been associated with a high false-positive rate. One study found that 16 of 31 positive Gram stains were false positives and that only one Gram stain out of nearly 800 led to a change in antimicrobial therapy [53]. However, a Gram stain can help differentiate SBP from secondary bacterial peritonitis due to intestinal perforation; in the latter, the Gram stain may show multiple different bacterial forms (picture 1).

●Bacterial culture – We send ascitic fluid for culture in blood culture bottles. We typically use a minimum of 10 mL of ascitic fluid for each bottle.  

We inoculate at least two bottles (one for aerobic and one for anaerobic culture) immediately at the bedside using a new, sterile needle. We do not use a needle that has passed through the skin to inoculate the bottles because it may contaminate the fluid sample with skin flora.

The technique of sampling ascitic fluid for microbial culture includes preparing the culture bottles, aspirating the ascitic fluid from the abdominal cavity, transferring the fluid to the culture bottle, and submitting the specimens to the laboratory:

•Immediately prior to the paracentesis, cleanse the top of each blood culture bottle with an alcohol wipe and leave the wipe on the bottle top to maintain sterile conditions.

•During the paracentesis, connect a syringe (usually a 50 mL syringe) to the needle in the abdominal wall and aspirate ascitic fluid. Begin by collecting the sample for microbiologic testing. Additional fluid is obtained for other testing (eg, cell count and chemistries). (See 'Cell count with differential' above and 'Chemistries' above.)

•After obtaining the fluid sample, attach a new, sterile needle to the syringe. The new needle can be used to inoculate multiple bottles.

•Remove the alcohol wipes from the top of the blood culture bottles and inoculate each bottle with at least 10 mL of ascitic fluid. However, some bottles may reach their maximum fluid capacity before injecting 10 mL, in which case it may be required to inoculate the bottles with less than 10 mL.

•Send the culture bottles to the microbiology laboratory for both aerobic and anaerobic culture.

We use blood culture bottles because SBP is a low-colony-count monomicrobial infection similar to bacteremia. Inoculating blood culture bottles with ascitic fluid at the bedside has been associated with higher diagnostic yield than sending ascitic fluid alone (eg, in a syringe or tube) for culture [52]. In a study of patients with an ascitic fluid neutrophil count ≥250 cells/microL, immediate bedside inoculation was associated with increased rates of positive ascitic fluid culture compared with delayed (laboratory) inoculation (100 versus 76 percent) [52,54].

The volume of fluid cultured also impacts the sensitivity of ascitic fluid cultures. In one report, for example, inoculating 10 or 20 mL of fluid into 100 mL blood culture bottles led to a higher culture-positivity rate compared with 1 mL inoculum (93 versus 53 percent) [55].

●Role of mycobacterial (eg, tuberculosis) tests – If tuberculous peritonitis is suspected, we send ascitic fluid for an acid-fast bacteria (AFB) smear and mycobacterial culture. The sensitivity of these tuberculosis tests is low. If tuberculous peritonitis is suspected, a peritoneal biopsy specimen using other methods (eg, laparoscopy, radiographic-guided interventions) is often necessary. The diagnostic evaluation of patients with suspected tuberculous peritonitis is discussed separately. (See "Abdominal tuberculosis".)

Role of blood tests, including blood cultures — For initial blood tests, we obtain complete blood count with differential, serum albumin, electrolytes, kidney function, liver enzymes, serum bilirubin, and serum glucose. These tests are useful for general clinical evaluation and management, but they are not necessary to establish the diagnosis of SBP. Peripheral blood cultures are not needed routinely but can be informative if they return positive. (See 'Establishing the diagnosis' above.)

Role of imaging — Imaging beyond the use of transabdominal ultrasound to perform the paracentesis is not required. We typically obtain imaging in selected patients (eg, those with suspected secondary peritonitis), and specific imaging tests are discussed below. (See 'Distinguishing SBP from secondary bacterial peritonitis' below.)  

Subsequent testing for selected patients — For patients who do not improve symptomatically within 48 hours despite appropriate empiric antibiotic therapy, we repeat the diagnostic paracentesis, compare the ascitic fluid neutrophil count to the pretreatment value, and assess the initial ascitic fluid culture results (if available) [56,57]:

●Patients with no or minimal decrease in neutrophil count – If there is no or minimal (<25 percent) decrease in ascitic fluid neutrophil count and/or the initial culture grows multiple organisms (especially if Enterococcus species or fungi are among the flora), secondary peritonitis related to an intra-abdominal process should be suspected. For such patients, we obtain imaging with a contrast-enhanced CT scan of the abdomen and pelvis. (See 'Distinguishing SBP from secondary bacterial peritonitis' below.)

An alternative cause for persistently elevated ascitic fluid neutrophil count is that the empiric antibiotic regimen does not penetrate ascitic fluid well or does not adequately cover the bacterial flora. Rates of nonresponse to empiric antimicrobial therapy for SBP have been increasing over time and have been associated with increased risk of mortality [56,57]. Selecting empiric antibiotic therapy is informed by the patient’s severity of illness and risk of infection with a multidrug-resistant organism, and these issues are discussed separately. (See "Spontaneous bacterial peritonitis in adults: Management".)

●Patients with improved neutrophil count – If the ascitic fluid neutrophil count is lower than the pretreatment value by at least 25 percent, the patient likely has SBP. For such patients, the initial ascitic fluid culture typically isolates one organism, while the follow-up ascitic fluid culture will usually be sterile.

For patients who are not improving clinically despite an improved neutrophil count, we evaluate for another source of symptoms, and the workup is guided by the symptomatology (eg, fever, alteration in mental status). (See "Fever of unknown origin in adults: Evaluation and management".)  

DISTINGUISHING SBP FROM SECONDARY BACTERIAL PERITONITIS — 

Some patients with cirrhosis and ascitic fluid neutrophil count ≥250 cells/microL may have secondary bacterial peritonitis related to a perforated viscus or an infected intra-abdominal organ (eg, perinephric abscess).

Secondary peritonitis is less common than SBP and accounts for less than 5 percent of all cases of peritonitis in patients with cirrhosis [58,59].

Distinguishing secondary peritonitis from SBP involves clinical assessment, prompt abdominal imaging (ie, contrast-enhanced computed tomography scan of the abdomen), and analyzing ascitic fluid test results (algorithm 1):

●Abdominal symptoms and signs – Most patients with a perforated viscus or intra-abdominal abscess develop symptoms such as abdominal pain, abdominal distension, and/or abdominal tenderness on physical examination [59].

The pain may be more severe than that seen with SBP. However, in some patients, symptoms may be subtle because ascitic fluid separates the visceral peritoneum from the parietal peritoneum and may prevent the development of rebound tenderness. (See "Overview of gastrointestinal tract perforation".)

●Imaging – The diagnosis of secondary peritonitis can often be established by imaging (algorithm 1). We typically obtain imaging (ie, contrast-enhanced computed tomography scan of the abdomen and pelvis) in patients with any of the following:

•Signs of acute abdomen (abdominal tenderness with rebound)

•Hemodynamic instability

•Ascitic fluid analysis suggestive of secondary peritonitis (eg, bile-stained ascites, elevated total protein, elevated LDH, low glucose) (table 1)

Imaging that demonstrates a perforated viscus or infectious process involving an abdominal organ is consistent with secondary peritonitis. Findings of perforated viscus include extraluminal gas and/or disruption of the intestinal wall.

Of note, performing paracentesis may also introduce small amounts of extraluminal gas into the abdominal cavity. Thus, we use multidisciplinary discussion (eg, hepatology, surgery, radiology) to manage patients with such findings.

●Ascitic fluid testing – Ascitic fluid in patients with secondary peritonitis may show the following (table 1) [59]:

•High total protein concentration in ascitic fluid (>1 g/dL (10 g/L).

•Low glucose <50 mg/dL (2.8 mmol/L). In patients with a perforated viscus, the ascitic fluid glucose concentration may fall to near zero [60]. Because neutrophils may consume large quantities of glucose, the concentration of neutrophils in ascitic fluid and their magnitude of activity are generally inversely correlated with the glucose concentration [50].  

•Bile stained ascitic fluid with bilirubin concentration >6 mg/dL (>103 micromol/L).

•Very high ascitic fluid neutrophil count (eg >4000 cells/microL).

•Polymicrobial infection on ascitic fluid culture (or Gram stain showing large numbers of different bacterial forms) (picture 1).

•Elevated amylase.

Proposed laboratory criteria for diagnosis of secondary bacterial peritonitis (sometimes referred to as Runyon criteria) include at least two of the following ascitic fluid findings [60]:

•Total protein >1 g/dL (10 g/L).

•Glucose <50 mg/dL (2.8 mmol/L).

•LDH >the upper limit of normal for serum LDH.

Studies suggested that these criteria are specific for secondary bacterial peritonitis. In a study evaluating 24 patients with cirrhosis and secondary bacterial peritonitis compared with 106 patients with SBP, the sensitivity and specificity of these criteria for predicting secondary bacterial peritonitis were 67 and 96 percent, respectively [58]. Nearly all patients (96 percent) with secondary peritonitis fulfilled at least two of the three criteria and/or had polymicrobial ascitic fluid culture.

Hospitalized patients with cirrhosis who develop peritonitis while receiving broad-spectrum parenteral antibiotics are more likely to have secondary bacterial peritonitis. SBP is typically sensitive to appropriate antimicrobial therapy and is unlikely to develop in the setting of broad-spectrum antibiotics. (See "Overview of gastrointestinal tract perforation".)

DIFFERENTIAL DIAGNOSIS — 

Other causes of infectious peritonitis include:

●Secondary bacterial peritonitis – Peritonitis due to an intra-abdominal infectious process (eg, perforated viscus, infected intra-abdominal organ) may mimic SBP, and it is important to recognize secondary peritonitis due to the risk of adverse outcomes. (See 'Distinguishing SBP from secondary bacterial peritonitis' above.)

●Candida peritonitis – Candida species frequently contribute to polymicrobial infections that occur following surgery on the gastrointestinal tract. Intestinal perforation, anastomotic leaks, and acute necrotizing pancreatitis are also associated with intra-abdominal candidiasis. The diagnosis is usually made by analysis of fluid that was aspirated at the time of surgery or with imaging guidance. (See "Candida infections of the abdomen and thorax".)

●Tuberculous peritonitis – Tuberculous peritonitis may be associated with an elevated ascitic fluid neutrophil count. However, the cell count in tuberculous ascites consists predominantly of lymphocytes and usually ranges from 150 to 4000 cells/microL. In addition, the ascitic fluid usually has a total protein concentration >3 g/dL (30 g/L), and most patients do not develop fever. (See "Abdominal tuberculosis".)

●Infected pancreatic ascites – Pancreatitis with disrupted pancreatic ducts can result in large-volume ascites that can become infected. The key distinguishing feature is a high amylase concentration (ie, >1000 units/L) in pancreatic ascites. (See "Chylous, bloody, and pancreatic ascites", section on 'Pancreatic ascites'.)

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Portal hypertension and ascites".)

SUMMARY AND RECOMMENDATIONS

●Background and risk factors – Spontaneous bacterial peritonitis (SBP) is an ascitic fluid infection that occurs in the absence of an obvious source of infection. SBP primarily occurs in patients with cirrhosis complicated by portal hypertension and ascites. (See 'Introduction' above.)

Risk factors for SBP include:

•Severity of cirrhosis (eg, Child-Pugh score ≥9 points, total serum bilirubin ≥3 mg/dL [51 micromol/L]) (calculator 1 and calculator 2)

•Ascitic fluid total protein concentration <1 g/dL (10 g/L)

•Prior episode of SBP

•Upper gastrointestinal bleeding

•Malnutrition (see "Nutritional issues in adult patients with cirrhosis", section on 'Nutrition assessment')

●Clinical features – Symptoms of SBP may be subtle because ascitic fluid separates the visceral peritoneum from the parietal peritoneum. Up to one-third of patients with SBP have no symptoms or signs of infection.

Common symptoms include abdominal pain, abdominal tenderness on palpation, fever, and altered mental status. The presence of ileus, hypotension, and hypothermia may indicate more severe infection. (See 'Clinical features' above.)

●Diagnostic evaluation – SBP should be suspected in patients with cirrhosis and ascites with any of the following (see 'Diagnosis' above):

•Symptoms and signs of SBP such as abdominal pain, fever, altered mental status, abdominal tenderness, hypotension, or hypothermia.

•A condition requiring nonelective or emergency hospitalization (eg, acute gastrointestinal bleeding, acute kidney injury).

•Laboratory abnormalities such as peripheral leukocytosis, metabolic acidosis, or azotemia.

Obtaining ascitic fluid promptly for laboratory testing is the cornerstone of the evaluation of patients with suspected SBP.

Abdominal paracentesis is a bedside procedure in which a needle is inserted into the peritoneal cavity and ascitic fluid is removed. Technical aspects and adverse events related to diagnostic paracentesis are discussed separately. (See "Diagnostic and therapeutic abdominal paracentesis".)

The ascitic fluid should be tested for the following (table 1):

•White blood cell count and differential.

•Microbiologic tests including Gram stain and culture.

•Fluid chemistries including albumin and protein. Additional tests (eg, glucose, lactate dehydrogenase, amylase, bilirubin) can help to evaluate persistent infection or differentiate SBP from secondary peritonitis. (See 'Distinguishing SBP from secondary bacterial peritonitis' above.)

●Establishing the diagnosis – The diagnosis of SBP is established by an ascitic fluid neutrophil count ≥250 cells/microL. We obtain ascitic fluid cultures to inform antimicrobial therapy. However, we begin antibiotic therapy for all patients with an ascitic neutrophil count ≥250 cells/microL while awaiting ascitic fluid culture results. (See 'Establishing the diagnosis' above and "Spontaneous bacterial peritonitis in adults: Management".)

When the diagnosis of SBP is uncertain, we obtain additional tests (eg, cross-sectional abdominal imaging) to differentiate SBP from secondary bacterial peritonitis (algorithm 1). (See 'Distinguishing SBP from secondary bacterial peritonitis' above.)

ACKNOWLEDGMENT — 

The UpToDate editorial staff acknowledges Bruce Runyon, MD, FAASLD, who contributed to earlier versions of this topic review.