Spontaneous Bacterial Peritonitis

• Translocation of gram-negative enteric organisms across the intestinal mucosa represents the primary mechanism. Portal hypertension causes structural and functional changes in the intestinal epithelium, including increased permeability, blunted intestinal peristalsis, and bacterial overgrowth (increased intraluminal bacterial concentrations 100-1000 fold higher than normal). Gram-negative aerobic organisms (predominantly Escherichia coli, Klebsiella, Enterobacter) and gram-positive organisms (Staphylococcus aureus, streptococci) translocate through the intestinal wall via lymphatic and hematogenous routes. The splanchnic vasodilation characteristic of advanced cirrhosis impairs the reticuloendothelial clearance of translocated bacteria, allowing pathogenic organisms to reach the peritoneal cavity. This mechanism explains why SBP is rare in ascites from non-cirrhotic causes with intact hepatic and splenic filtration function.

• Severe impairment of ascitic fluid opsonic activity and complement function creates a permissive environment for bacterial proliferation once organisms reach the peritoneal cavity. Cirrhotic ascites contains markedly reduced levels of complement (particularly C3 and C4), reduced opsonins (including fibronectin and immunoglobulins), and decreased lysozyme activity compared to serum. The ascitic fluid-to-serum ratio of complement components is inversely proportional to mortality risk. Patients with ascitic fluid total protein <1.5 g/dL (reflecting low immunoglobulin and complement content) have markedly impaired bacterial clearance. The reduced protein content correlates with decreased opsonic capacity, as serum complement (particularly IgG and complement proteins) is selectively filtered into ascitic fluid based on molecular size and concentration gradients.

• Impaired cellular immune function in advanced cirrhosis reduces the ability of resident peritoneal macrophages and infiltrating polymorphonuclear leukocytes to control bacterial growth. Cirrhotic patients demonstrate decreased neutrophil chemotaxis, impaired phagocytic capacity, and reduced oxidative burst activity. The mononuclear phagocyte system dysfunction in cirrhosis impairs the clearance of opsonized bacteria. Portal hypertension and hypersplenism lead to relative immunoglobulin deficiency and altered T-cell function. Bacterial lipopolysaccharide (LPS) stimulation in cirrhosis triggers a dysregulated inflammatory response with exaggerated TNF-α production from Kupffer cells, perpetuating systemic inflammation (SIRS) despite impaired local bacterial killing capacity.

• Reduced ascitic fluid volume and stasis in some patients creates localized "pools" of infection. Low-protein ascites has reduced oncotic pressure and may accumulate slowly, allowing organisms to establish infection without significant dilution. The altered peritoneal blood flow in portal hypertension may reduce delivery of opsonins and immune cells to affected areas.

• Disruption of normal flora barriers through antibiotic use, proton pump inhibitors (increasing gastric pH), and altered intestinal motility promote overgrowth of pathogenic organisms. Selective intestinal decontamination studies demonstrate the critical role of gram-negative flora in SBP pathogenesis.

• Cirrhosis with ascites is the major risk factor, accounting for >95% of SBP cases. Risk is stratified by hepatic synthetic function: Child-Pugh C (advanced cirrhosis) carries significantly higher risk than earlier stages. The etiology of cirrhosis (alcoholic, hepatitis C, hepatitis B, primary biliary cholangitis, primary sclerosing cholangitis) does not substantially alter SBP risk, though advanced stage is the critical determinant. Ascites volume and composition matter; large-volume ascites and ascites with low total protein (<1.5 g/dL) carry higher risk due to reduced complement and opsonin content.

• Previous SBP episode is one of the strongest risk factors for recurrence, with approximately 40-70% of patients experiencing recurrence within 1 year without prophylaxis. The recurring infection mechanism mirrors the initial episode: persistent immune dysfunction, continued bacterial translocation, and reduced ascitic defenses.

• Low ascitic fluid total protein (<1.5 g/dL) is an independent risk factor for both SBP development and mortality. This reflects reduced passive transfer of complement, immunoglobulins, and fibronectin into ascites. Some guidelines recommend prophylaxis for high-risk patients with protein <1.5 g/dL and advanced liver disease (Child-Pugh >9 or bilirubin >3 mg/dL).

• Upper gastrointestinal hemorrhage is a potent precipitant of SBP. The proposed mechanisms include: increased bacterial translocation (impaired intestinal barrier after hemorrhage), reduced opsonin transfer to ascites, increased endotoxemia triggering splanchnic vasodilation and further immune dysfunction, and bacterial overgrowth in the setting of blood as a nutritional substrate. Patients with variceal bleeding have reported SBP incidence up to 46% in some series without antibiotic prophylaxis.

• Renal failure (hepatorenal syndrome, acute kidney injury) substantially increases SBP risk through multiple mechanisms: reduced glomerular filtration of bacteria-derived LPS, impaired synthesis of complement and opsonins, and increased bacterial translocation secondary to intestinal edema and dysbiosis. Conversely, SBP can precipitate renal failure through worsening systemic inflammation and splanchnic vasodilation.

• Immunosuppressive conditions beyond cirrhosis increase risk. Patients with Human Immunodeficiency Virus (HIV) infection (particularly with CD4 <200 cells/μL) and ascites have elevated SBP incidence. Malignancy-related ascites carries rare but documented SBP risk.

• Other ascitic infections predisposing to secondary bacterial peritonitis (perforated viscus, appendicitis, pancreatitis) must be distinguished from primary SBP. Secondary peritonitis occurs in 5-10% of peritonitis cases in cirrhotic patients and carries worse prognosis due to polymicrobial flora.

• Fever (temperature >38.5°C) occurs in approximately 50-80% of SBP cases but is conspicuously absent in 20-50% of presentations, making afebrile peritonitis a critical clinical trap. The impaired cytokine response in advanced cirrhosis may blunt fever despite significant infection. Fever when present reflects bacterial stimulation of pyrogenic cytokine (TNF-α, IL-1) release from activated macrophages, though the response is attenuated compared to immunocompetent hosts.

• Abdominal pain is present in 50-60% of patients but may be subtle or absent. Pain location varies (diffuse, localized to right lower quadrant, epigastric) and severity may not correlate with infection severity. The pain reflects peritoneal inflammation and irritation from bacterial lipopolysaccharide and host inflammatory response. Importantly, patients with cirrhotic peritonitis may have baseline abdominal discomfort from ascites itself, making assessment challenging.

• Abdominal tenderness on examination is elicited in only 40-50% of cases—far lower than in immunocompetent patients with bacterial peritonitis. When present, findings range from mild diffuse tenderness to peritoneal signs (rebound, guarding), but their absence does NOT exclude SBP. Rebound tenderness and guarding are relatively specific (>80%) but insensitive (~40%) findings. The muted peritoneal signs reflect reduced local inflammatory response in immunocompromised hosts.

• Altered mental status and encephalopathy may develop acutely with SBP, particularly if the patient had prior episodes of hepatic encephalopathy. The mechanism involves increased ammonia production from bacterial overgrowth and increased intestinal permeability to ammonia-producing organisms, combined with activation of GABA-ergic pathways by endotoxemia. Encephalopathy may be the presenting sign, especially in elderly patients or those with advanced liver disease.

• Spontaneous deterioration in clinical status without clear precipitant often heralds SBP. This includes unexpected decompensation, progressive azotemia (hepatorenal syndrome), worsening coagulopathy, thrombocytopenia, or hemodynamic instability. Tachycardia, hypotension, tachypnea, and signs of sepsis may develop as the infection progresses, reflecting systemic inflammatory response and splanchnic vasodilation.

• Gastrointestinal symptoms such as nausea, vomiting, or diarrhea may accompany SBP, reflecting bacterial translocation and intestinal inflammation.

• Asymptomatic presentations represent a significant minority (up to 20-30%) of SBP cases, with infection discovered incidentally on routine paracentesis in hospitalized cirrhotic patients. This underscores the critical importance of diagnostic paracentesis in any cirrhotic patient with unexplained deterioration, even without clear abdominal signs.

• Diagnostic paracentesis is the gold standard and absolutely essential. All cirrhotic patients admitted to hospital or with clinical decompensation should undergo paracentesis; this is one of the most board-tested principles. The procedure is safe (bleeding complications <1%, perforation extremely rare) and should not be delayed. Contraindications are extremely rare in cirrhotic patients; even modest coagulopathy is not an absolute contraindication given the low bleeding risk. Obtain 10-20 mL of ascitic fluid in sterile tubes (two culture bottles for bacterial culture, one tube in ethylenediaminetetraacetic acid [EDTA] for cell counts, one tube plain for chemistry and Gram stain).

• Ascitic fluid PMN cell count >250 cells/μL is the diagnostic criterion for SBP in most guidelines (American Association for the Study of Liver Diseases [AASLD], European Association for the Study of the Liver [EASL]). This threshold was derived from studies showing that counts >250 cells/μL have ~97% sensitivity and ~99% specificity for bacterial infection. Critically, the diagnosis is based on cell count, not culture results, as bacterial cultures are positive in only 40-60% of cases despite clear PMN elevation. False positives (PMN elevation without infection) are rare (<1-2%) and usually reflect hemoperitoneum (blood in the ascites, where each red blood cell adds approximately 1 PMN equivalent). The PMN count should include all neutrophils (segmented and bands).

• Ascitic fluid total protein <1.5 g/dL is associated with higher SBP incidence and poor prognosis but is not required for diagnosis. Low protein reflects reduced opsonin content and predicts recurrence risk.

• Ascitic fluid culture should be obtained but is positive in only 40-60% of cases and should not delay treatment initiation. When culture is positive, it reliably identifies the organism and allows antibiotic tailoring. Gram-negative organisms predominate (60-70% of cultured cases), with E. coli most common (30-40% of cases), followed by Klebsiella, Enterobacter, and other enteric gram-negatives. Gram-positive organisms (Staphylococcus, streptococci) account for 20-30% of cases, with Streptococcus pneumoniae and viridans group streptococci most frequent. Anaerobes are rare (<5%) unless there is communication with a perforated viscus (suggesting secondary peritonitis). Culture sensitivity is improved by inoculating ascitic fluid directly into blood culture bottles at the bedside or sending samples promptly to the laboratory. Some laboratories recommend sending a larger volume (≥20 mL) per bottle.

• Ascitic fluid Gram stain has poor sensitivity (40-50%) but is rapid; its use is declining with faster culture techniques.

• Serum creatinine, bilirubin, albumin, and coagulation studies provide prognostic information. Renal failure (creatinine >1.5 mg/dL at presentation or increase of ≥1 mg/dL during hospitalization) and elevated bilirubin independently predict mortality. The MELD score and Child-Pugh score correlate with outcome.

• Serum procalcitonin and C-reactive protein (CRP) may support the diagnosis in equivocal cases (PMN count borderline, 200-250 cells/μL) but are not required for standard diagnosis. Elevated serum procalcitonin (>0.5 ng/mL) and CRP (>6 mg/dL) increase diagnostic confidence for SBP.

• Imaging (ultrasound, CT) is not required for SBP diagnosis but may reveal: ascites characteristics (echogenicity suggesting hemoperitoneum if cultured RBC/WBC ratio differs markedly from peripheral blood), loculated fluid suggesting abscess formation, or signs of secondary peritonitis (free air, visceral perforation, diverticulitis, appendicitis). Ultrasound-guided paracentesis should be used if ascites is loculated or if the operator is inexperienced.

• Diagnostic criteria for SBP (AASLD 2012 revised criteria):
• Ascitic fluid PMN count ≥250 cells/μL (previously ≥500 cells/μL in older literature)
• With or without positive culture
• Without perforation or other surgically remediable source
• Typically in setting of cirrhotic ascites

• Variants and differential considerations:
• Culture-negative PMN ascites (CNPA): PMN ≥250 cells/μL but culture negative; represents 30-40% of SBP cases and should be treated identically as culture-positive SBP
• Monomicrobial non-neutrocytic bacterascites (MNNCB): Positive culture but PMN <250 cells/μL; prognosis is better than classic SBP but 30-40% progress to SBP; requires follow-up and repeat paracentesis
• Polymicrobial bacterascites: Multiple organisms on culture (suggests secondary peritonitis) requiring imaging to exclude perforation
• Secondary bacterial peritonitis: Associated with surgical pathology (perforation, appendicitis, pancreatitis); typically has multiple organisms (anaerobes, gram-negatives, gram-positives), PMN usually >1000 cells/μL, higher protein content, and should trigger imaging investigation

• When to perform paracentesis: All cirrhotic patients presenting with fever, abdominal pain, unexplained deterioration (encephalopathy, renal failure, acidosis), gastrointestinal hemorrhage, spontaneous worsening of clinical status, or hospitalization. Current guidelines recommend paracentesis on all cirrhotic patients admitted to hospital given the high prevalence of occult infection.

• Empiric third-generation cephalosporin is the first-line antibiotic and should be initiated immediately upon suspicion of SBP, without waiting for culture results. Cefotaxime 2 g intravenously every 4-6 hours (standard dose 2 g IV q6h for 5-7 days) or ceftriaxone 1-2 g IV daily are preferred. These agents provide excellent coverage of gram-negative enteric organisms (E. coli, Klebsiella) which cause 60-70% of cases, and reasonable gram-positive coverage. Third-generation cephalosporins penetrate ascitic fluid well. Cephalosporin therapy is superior to older regimens (ampicillin plus gentamicin, chloramphenicol) with better outcomes and tolerability. If the patient is severely penicillin-allergic (anaphylaxis), **fluoroquinolones

Emergencies — recognize immediately

• Hepatorenal syndrome–acute kidney injury (HRS-AKI): the most feared complication, occurring in roughly a third of untreated episodes. Infection-driven cytokine release worsens splanchnic vasodilation, dropping effective arterial blood volume and triggering renin–angiotensin and sympathetic-mediated renal vasoconstriction. Signaled by a rising creatinine that does not correct with volume, with a bland urine sediment and low urine sodium. AASLD guidance recommends intravenous albumin (1.5 g/kg at diagnosis, 1 g/kg on day 3) to prevent it, with the greatest benefit in patients with creatinine >1 mg/dL, BUN >30 mg/dL, or bilirubin >4 mg/dL. Established HRS-AKI is treated with a vasoconstrictor plus albumin and is a transplant-evaluation trigger.
• Septic shock and multiorgan failure: endotoxemia superimposed on the already vasodilated cirrhotic circulation produces refractory hypotension and lactic acidosis; this is acute-on-chronic liver failure when two or more organ systems fail.
• Missed secondary bacterial peritonitis: a perforated viscus masquerading as SBP will not respond to antibiotics alone and requires imaging and surgical source control. Suspect it when the fluid is polymicrobial, PMNs are very high, or Runyon's criteria are met (total protein >1 g/dL, glucose <50 mg/dL, LDH above the serum upper limit).

Other complications

• Treatment failure: a repeat paracentesis at 48 hours showing failure of the PMN count to fall substantially indicates a resistant organism (health-care–associated ESBL producers, prior quinolone prophylaxis) or secondary peritonitis; broaden coverage and image.
• Hepatic encephalopathy and variceal hemorrhage: infection raises ammonia and portal pressure; encephalopathy may be the only clue.
• Recurrence: very common within a year without secondary prophylaxis.
• Therapy-related harms: Clostridioides difficile colitis and selection of quinolone-resistant flora from long-term prophylaxis; nephrotoxicity if aminoglycosides are used — avoid them in cirrhosis; volume overload/pulmonary edema from large albumin loads in patients with cardiac dysfunction.

• Single best next step in any cirrhotic with ascites who deteriorates: diagnostic paracentesis, before antibiotics. Fever, abdominal pain, new encephalopathy, unexplained AKI, hypotension, or simply hospital admission all qualify. Coagulopathy is not a reason to defer — do not "correct the INR with FFP first," the classic distractor.
• PMN ≥250 cells/μL makes the diagnosis, culture or no culture. Culture-negative neutrocytic ascites is treated identically. Conversely, a positive culture with PMN <250 (bacterascites) is monomicrobial and often transient — repeat the tap.
• Bloody tap correction: subtract one PMN for every ~250 red cells before applying the 250 threshold.
• Monomicrobial gram-negative growth = SBP; polymicrobial growth with anaerobes = secondary peritonitis until proven otherwise. E. coli is the single most common isolate. Secondary peritonitis needs CT and surgery, not just cefotaxime.
• The association examiners love: SBP plus albumin. AASLD supports intravenous albumin (1.5 g/kg at diagnosis, 1 g/kg on day 3) alongside a third-generation cephalosporin because it prevents hepatorenal syndrome and reduces mortality, especially with creatinine >1 mg/dL, BUN >30 mg/dL, or bilirubin >4 mg/dL.
• Prophylaxis triads: (1) acute GI bleeding in cirrhosis → short-course ceftriaxone; (2) prior SBP → indefinite secondary prophylaxis with a fluoroquinolone or trimethoprim-sulfamethoxazole until transplant or resolution of ascites; (3) ascitic protein <1.5 g/dL with advanced liver or renal dysfunction → primary prophylaxis.
• Common distractors to avoid: SBP is not a surgical disease and needs no laparotomy; aminoglycosides are the wrong empiric choice because of nephrotoxicity in cirrhosis; a negative Gram stain never excludes SBP; and absence of fever or abdominal tenderness does not rule it out.
• Modifiable contributor: unnecessary proton pump inhibitors raise gastric pH and promote small-bowel bacterial overgrowth — deprescribe them in cirrhotic ascites.