Spontaneous bacterial peritonitis

Spontaneous bacterial peritonitis (SBP) is a bacterial infection of ascitic fluid that occurs in the absence of an identifiable intraabdominal source of infection. It is the most common bacterial infection and a leading cause of hospital admission and mortality among patients with cirrhosis. Enteric gram-negative bacteria (e.g., E. coli, Klebsiella spp.) have historically been the most common isolates; however, gram-positive, fluoroquinolone-resistant, and multidrug-resistant bacteria are increasingly common. SBP may manifest with fever, abdominal pain, and/or altered mental status, but some patients are asymptomatic at presentation. Diagnosis is based on the finding of elevated ascitic fluid neutrophil count (≥ 250/mm³) without an intraabdominal surgically-treatable source of infection. Timely antibiotic administration is the mainstay of therapy. Empiric antibiotic choice depends on the setting of infection (i.e., community-acquired infection vs. healthcare-associated infection), previous antibiotic exposure, and local bacterial susceptibility patterns. IV albumin supplementation is used as adjunctive therapy. Long-term prophylactic antibiotic therapy is recommended to prevent recurrent infection.

• Spontaneous bacterial peritonitis: : infection of the ascitic fluid in the absence of any focal intraabdominal, surgically treatable source of infection ^[1]
• Secondary bacterial peritonitis: inflammation of the peritoneum caused by bacterial infection from a surgically treatable intraabdominal source ^[2]

• Most common bacterial infection in patients with cirrhosis. ^[3]
• Represents over 30% of bacterial infections among hospitalized patients with cirrhosis. ^[4]
• Prevalence among asymptomatic outpatients with decompensated cirrhosis is estimated to be up to 3.5% ^[5]

Epidemiological data refers to the US, unless otherwise specified.

Risk factors ^[3]

SBP in adults occurs almost exclusively in patients with cirrhosis and ascites. ^[6]

• Additional risk factors in patients with cirrhosis include: ^[3]
  • Low ascitic fluid protein concentration (< 1.5 g/dL)
  • Upper gastrointestinal bleeding
  • Prior episodes of SBP

Pathophysiology ^[3][7]

• Bacterial translocation from the intestinal lumen to mesenteric lymph nodes →; spread to systemic and portal circulation → colonization and subsequent infection of ascitic fluid
• Contributing factors related to underlying portal hypertension and cirrhosis:
  • Intestinal dysmotility
  • Bacterial overgrowth
  • Altered intestinal permeability
  • Systemic immune dysfunction

Microbiology ^[3][7]

• Usually a monomicrobial infection; suspect secondary bacterial peritonitis if multiple organisms are demonstrated on ascitic fluid gram stain or culture (see “Secondary bacterial peritonitis” in “Differential diagnoses” section).
• Gram-negative enteric bacteria (e.g., Escherichia coli, Klebsiella spp.) are most common.
• Gram-positive bacteria (e.g., Streptococcus spp., Staphylococcus spp., Enterococcus spp.) are increasing in prevalence.
• Increasing prevalence of fluoroquinolone-resistant and multidrug-resistant bacteria ^[8][9]

SBP is typically a monomicrobial bacterial infection. The presence of multiple organisms on ascitic fluid gram-stain or culture should raise suspicion for secondary bacterial peritonitis.

Symptoms and signs of SBP may be subtle or absent.

• Diffuse abdominal pain/tenderness
• Fever and chills
• Worsening ascites
• New-onset or worsening encephalopathy
• Jaundice
• Nausea, vomiting
• Constipation or diarrhea (peristaltic signs sparse or absent in cases of ileus)

SBP is diagnosed when the ascitic fluid neutrophil count is ≥ 250/mm³, with or without positive ascitic fluid bacterial cultures, and in the absence of another intraabdominal source of infection. SBP is often asymptomatic and a high index of suspicion is essential in any patient with cirrhosis and ascites. ^[3]

Approach ^[10][11]

• Assess for and, if present, initiate management of septic shock.
• Obtain 2 sets of blood cultures before the administration of antibiotics.
• Perform paracentesis without delay and before the administration of antibiotics. ^[12][13]
• Rule out secondary bacterial peritonitis (see the section “Differential diagnosis”) and other causes of abdominal pain (see “Acute abdominal pain”). ^[14]

Laboratory studies

• Blood cultures (2 sets)
• Inflammatory markers (e.g., CRP, ESR) may be elevated ^[15]
• CBC: potentially leukocytosis
• Liver chemistries: findings consistent with cirrhosis (see “Diagnostics” in “Cirrhosis”); evaluate for worsening hepatic function
• Basic metabolic panel: to evaluate for acute kidney injury, hepatorenal syndrome, hyponatremia
• Coagulation panel

Peritoneal fluid analysis ^[3][10][11]

• Obtained via diagnostic paracetensis
• When indicated, perform this procedure as soon as possible (ideally before the administration of antibiotics).
• See “Paracentesis” for further details on indications, contraindications, steps, troubleshooting, and complications of this procedure.

Indications for diagnostic paracentesis in SBP

Patients with cirrhosis and ascites with any of the following: ^[2][11]

• Clinical deterioration or hospital admission ^[16]
• Signs of infection (e.g., fever; , hypothermia, tachycardia, tachypnea, shock, leukocytosis, acidosis)
• Gastrointestinal signs or symptoms (e.g., abdominal pain/tenderness, vomiting, diarrhea, ileus, GI bleed)
• Encephalopathy
• Worsening ascites
• Worsening liver and/or renal function

Peritoneal fluid analysis in SBP

• Cell count and differential: neutrophil count of ≥ 250/mm³ indicates SBP
  • If the ascitic fluid is bloody (i.e., RBC > 10³/mm³), calculate the corrected neutrophil count by subtracting one neutrophil for every 250 RBCs. ^[17]
• Gram stain: limited value; very low sensitivity and high false-positive rates. ^[18]
• Bacterial cultures: often negative
  • Positive cultures not required for diagnosis but should be ordered in every patient suspected of having SBP ^[19]
  • Bacterascites
    • Definition: a positive ascitic fluid bacterial culture in the presence of ascitic fluid neutrophil count < 250/mm³ that is not associated with a surgically treatable intraabdominal source of infection
    • Interpretation: Bacterascites may represent transient bacterial colonization or early SBP. ^[20][21]
• Other
  • Albumin: serum-ascites albumin gradient (SAAG) > 1.1 indicates portal hypertension-related ascites.
  • Total protein, glucose, LDH: helpful in distinguishing SBP from secondary bacterial peritonitis (see “Differential diagnosis” section)

SBP is diagnosed when the ascitic fluid neutrophil count is ≥ 250/mm³ in the absence of another intraabdominal source of infection. The diagnosis of SBP does not require positive ascitic fluid cultures.

Imaging

Imaging tests are not required for diagnosis but may be indicated in patients with new-onset or worsening ascites (see ”Diagnostics” in “Cirrhosis”) or if secondary bacterial peritonitis is suspected (see “Differential diagnosis” section).

Antimicrobial therapy ^[10][11]

• Indications (presence of any of the following in a patient with cirrhosis and ascites): ^[10]
  • Strong suspicion for infection
    • Positive SIRS criteria, e.g., fever
    • Specific clinical features of SBP, e.g., abdominal pain and tenderness, AMS
  • Ascitic fluid neutrophil count ≥ 250/mm³
• Most common isolates: Escherichia coli, Streptococcus spp., Staphylococcus spp., and Klebsiella (see “Etiology” section) ^[9]
• Risk factors for resistant pathogens include: ^[2]
  • Nosocomial infection
  • Recent infection with multiresistant bacteria
  • Recent exposure to broad-spectrum antibiotics ^[10]
  • Long-term fluoroquinolone prophylaxis
• Duration
  • Narrow antibiotic coverage according to bacterial susceptibility.
  • Continue antibiotic therapy for at least 5–7 days. ^[22]

Empiric antibiotic therapy

Management of bacterascites ^[10][11]

• Start empiric antibiotic therapy only if signs/symptoms of infection are present (see “Empiric antibiotic therapy for SBP”). ^[10][11]
• If asymptomatic, repeat paracentesis after 48 hours and treat with antibiotics if repeat culture is positive. ^[20]

Empiric antibiotics are not indicated for asymptomatic patients with bacterascites.

Adjunctive therapy ^[10][11]

• IV albumin supplementation ^[2]
  • Indicated in all patients with SBP ^[10][26]
  • Particularly beneficial for patients with:
    • Total bilirubin > 5 mg/dL
    • Blood urea nitrogen > 30 mg/dL
    • Creatinine > 1 mg/dL
• Consider discontinuing beta blockers in patients with hypotension or AKI. ^[3][10][27]
• Discontinue diuretics. ^[3]
• Avoid potentially nephrotoxic medications (e.g., NSAIDs). ^[3]
• Consider discontinuing proton-pump inhibitors. ^[28]

Supportive therapy

• Electrolyte repletion
• Analgesics as needed (see “Pain management”)
• Antipyretics as needed
• IV fluids: Use caution in patients who are volume overloaded.
• See “Treatment” and “Complications” in “Cirrhosis” for other management considerations.

Monitoring and subsequent management ^[10][11]

• Serial abdominal examination
• Repeat paracentesis
  • Perform after 48 hours to assess response to antibiotics. ^[10][11]
  • A reduction of ascitic PMNs by less than 25% indicates a poor response.
• Consider secondary bacterial peritonitis in patients with:
  • Clinical deterioration despite first-line antibiotics
  • AND/OR insufficient reduction of PMNs on repeat paracentesis
• Consider GI/hepatology consult or infectious disease consult.
• Consider referral for a liver transplant evaluation. ^[29]

• Use ABCDE approach.
• Obtain blood cultures (2 sets) and routine laboratory studies (CBC, BMP, LFTs, coagulation panel).
• Perform paracentesis and order ascitic fluid analyses (cell count and differential, bacterial culture, total protein, albumin, glucose, LDH).
• Begin appropriate empiric antibiotic therapy for SBP.
• Consider CT abdomen/pelvis and surgical consult if any concern for secondary bacterial peritonitis.
• Consider consulting an infectious disease specialist.
• Administer IV albumin if appropriate (see “Adjunctive therapy” in “Treatment”).
• Hold diuretics and all potentially nephrotoxic medications. ^[10]
• Provide supportive therapy as needed
• Admit to a medical, GI/hepatology, or critical care service based on the patient's clinical status.
• Consider GI/hepatology consult.

Secondary bacterial peritonitis ^[2][11][13]

• Definition: inflammation of the peritoneum caused by bacterial infection from a surgically treatable intraabdominal source ^[2]
• Etiology:
  • Perforation of an intraabdominal viscus (e.g., duodenal perforation due to a peptic ulcer)
  • Translocation of bacteria from an abdominal organ inflammation (e.g., appendicitis, diverticulitis, pancreatitis, intraabdominal abscess)
  • Trauma (e.g., penetrating wound)
  • Iatrogenic (e.g., surgery, anastomosis insufficiency, invasive procedure)
• Clinical features
  • Abdominal pain/tenderness
  • Peritoneal signs (e.g., local or diffuse rigidity, rebound tenderness, and/or guarding) ^[30]
  • Gastrointestinal symptoms (e.g., nausea, vomiting, ileus)
  • Signs of infection (e.g., fever, tachycardia, tachypnea, hypotension, leukocytosis, sepsis, shock)
  • Worsening or lack of symptom resolution after initiation of antibiotics in a patient initially suspected of having SBP
• Diagnosis ^[2]
  • Cannot be reliably distinguished from SBP based on the clinical presentation and physical exam alone ^[13]
  • Peritoneal fluid analysis:
    • Cell count: neutrophil count of ≥ 250/mm³
    • Bacterial culture and/or gram stain: positive
    • Chemistries: total protein > 1 g/dL, LDH > upper limit of normal for serum, glucose < 50 mg/dL ^[13][31]
    • Other: Carcinoembryonic antigen > 5 ng/mL or alkaline phosphatase > 240 U/L suggests secondary peritonitis with intestinal perforation. ^[32]
  • Imaging:
    • CT scan of the abdomen and pelvis with IV contrast: indicated for any patient with suspected secondary bacterial peritonitis
    • X-ray abdomen (upright): Free air may be seen if viscous organ perforation is present.
• Management ^[2][11]
  • Start empiric broad-spectrum antibiotics: See “Empiric antibiotic therapy for intraabdominal infections” for approach and regimen options.
  • Consult surgery; for consideration of emergency laparotomy.
  • Provide supportive care.
    • IV fluids
    • Electrolyte repletion
    • Analgesics as needed (see “Pain management”)
    • Antipyretics as needed
    • VTE prophylaxis

Secondary bacterial peritonitis usually requires imaging and urgent surgical management.

Others

• Spontaneous fungal peritonitis
• Alcoholic hepatitis
• Other common infections in patients with cirrhosis ^[14]
  • Urinary tract infection
  • Pneumonia
  • Skin and soft tissue infection
  • Bacteremia
• Other conditions that may present with ascites accompanied by fever or abdominal pain ^[14]
  • Peritoneal carcinomatosis
  • Tuberculous peritonitis
  • Peritonitis complicating peritoneal dialysis in patients with end-stage renal disease
  • Pancreatic illness
  • Hepatic metastasis
  • Cardiac ascites
  • Nephrotic syndrome
• See also “Differential diagnosis” in “Acute abdomen” and “Fever.”

The differential diagnoses listed here are not exhaustive.

• Sepsis, septic shock, death
• Acute or chronic liver failure
• Acute kidney injury and/or hepatorenal syndrome
• Hepatic encephalopathy
• GI bleed
• Worsening ascites

We list the most important complications. The selection is not exhaustive.

Prophylaxis for SBP ^[2][11]

• Indications
  • Primary prophylaxis: ascitic fluid protein < 1.5 g/dL in patients with either impaired renal function or liver failure
  • Secondary prophylaxis: all patients with a previous episode of SBP ^[29]
  • Short-term prophylaxis in patients with cirrhosis and GI bleeding (see “Complications” in “Portal hypertension”)
• Commonly used agents
  • Ciprofloxacin ^[33]
  • Norfloxacin ^[2][33]
  • Trimethoprim/Sulfamethoxazole ^[33]