What is cholangitis?

What is Cholangitis?

Cholangitis is a potentially life-threatening bacterial infection of the intra- and/or extrahepatic bile ducts that arises from the combination of biliary obstruction and bacterial colonization, requiring urgent antibiotic therapy and biliary decompression to prevent sepsis and death. 1, 2

Pathophysiology

Biliary obstruction is the indispensable predisposing factor—without obstruction, cholangitis does not develop. 1, 3 The infection occurs when bacteria ascend from the intestine or reach the biliary system via the portal venous system, but this bacterial presence only becomes clinically significant when bile flow is impeded. 1

• High-grade biliary strictures with bile stagnation facilitate bacterial colonization and infection. 1
• Portal bacteremia, particularly in patients with active colitis, may contribute to biliary infection. 1

Common Etiologies

Choledocholithiasis (bile duct stones) represents the most frequent cause of the biliary obstruction that leads to cholangitis. 1, 3, 4

Other important causes include:

• Benign biliary strictures 5, 4
• Malignant biliary obstruction (particularly in patients with prior biliary instrumentation or stents) 5, 4
• Primary sclerosing cholangitis (PSC) with high-grade strictures 1
• ERCP-related instrumentation, especially with stent placement 1

Clinical Presentation

The classic presentation includes Charcot's triad: fever, jaundice, and right upper quadrant abdominal pain. 3, 4

• In severe cases, patients may progress to Reynolds' pentad (Charcot's triad plus hypotension and altered mental status), indicating life-threatening septic shock. 6, 4
• Laboratory findings typically show elevated inflammatory markers (leukocytosis, elevated CRP) and indicators of biliary stasis (elevated bilirubin and alkaline phosphatase). 3
• In PSC-associated cholangitis, signs can be mild and nonspecific, with patients sometimes presenting without significant changes in baseline liver biochemistry. 1

Diagnostic Approach

Diagnosis requires clinical signs, laboratory findings, and imaging evidence of biliary dilatation or an obstructing etiology such as stricture, stone, or mass. 3

• Ultrasound is the initial diagnostic imaging modality of choice. 3
• If ultrasound is equivocal and clinical suspicion persists, CT scan with IV contrast should be performed. 3
• MRCP is valuable for assessing biliary strictures, particularly when planning intervention. 1

Microbiology

The most common bacterial isolates are Enterococcus, E. coli, Enterobacter, and Klebsiella. 5

• Blood cultures are positive in 64% of cases and bile cultures in nearly all cases. 5
• Antibiotic resistance is common: 72% of patients have at least one resistant organism, and 36% have organisms resistant to multiple antibiotics. 5
• In PSC patients without prior instrumentation, bile cultures are usually negative; however, after ERCP, 60% have positive cultures. 1
• Gram-positive isolates (75%) predominate in PSC-associated cholangitis, contrasting with the enteric bacteria (74%) seen in choledocholithiasis-related cholangitis. 1

Treatment Principles

The two pillars of management are prompt antibiotic therapy and biliary decompression. 1, 3

Antibiotic Therapy

• Antibiotics must be administered within 1 hour for patients with septic shock. 6, 3
• For less severe cases, antibiotics should be given within 4-6 hours of diagnosis. 6, 3
• Recommended empiric regimens include 4th-generation cephalosporins, piperacillin/tazobactam, imipenem/cilastatin, meropenem, ertapenem, or aztreonam. 6
• Duration should be 7-10 days for uncomplicated cases, extended to 14 days if Enterococcus or Streptococcus is isolated. 6
• Blood and/or bile cultures should be routinely obtained to optimize antibiotic therapy given high resistance rates. 5

Biliary Decompression

ERCP with stent placement is the first-line procedure for biliary decompression (Recommendation 1A). 1, 6, 3

• ERCP achieves technical success rates exceeding 90%, with adverse event rates around 5% and mortality below 1%. 6
• Endoscopic drainage demonstrates significantly lower morbidity and mortality compared to open surgical drainage in severe cholangitis patients with hypotension and altered consciousness. 6
• During the acute phase, the goal should be biliary decompression only; definitive stone extraction should be deferred to avoid exacerbating sepsis. 6

Percutaneous transhepatic biliary drainage (PTBD) should be reserved as second-line therapy when ERCP fails or is not feasible (Recommendation 1B). 1, 6, 3

• PTBD carries significant risks including biliary peritonitis, hemobilia, pneumothorax, hematoma, liver abscesses, and catheter-related discomfort. 1, 6

Open surgical drainage is reserved only when both endoscopic and percutaneous routes have failed or are contraindicated. 6

Timing of Intervention

In severe (Grade III) cholangitis, early interventional biliary drainage is essential for survival and should be performed within 12-24 hours after hemodynamic stabilization. 1, 6, 3

• In moderate (Grade II) cholangitis, early decompression within 24 hours significantly reduces 30-day mortality. 6, 3
• Delayed intervention is associated with elevated morbidity and mortality rates, increased ICU admission, and prolonged hospitalization. 1, 3

Prognosis and Complications

Despite advances in antimicrobial therapy and biliary drainage techniques, mortality rates remain 11-15% in severe cases. 2, 4

• Cholangitis remains the second most common cause of community-acquired bacteremia and third most common cause of hospital-acquired bacteremia. 2
• In PSC patients, cholangitis was the most common disease-related clinical event, occurring in 13% over 23 months of follow-up. 1
• Recurrent cholangitis may accelerate disease progression and increase risk of biliary sepsis. 1

Critical Pitfalls to Avoid

• Never delay biliary drainage while awaiting "optimal" timing—postponement dramatically increases mortality in severe cholangitis. 6
• Do not attempt PTBD as first-line therapy when ERCP is feasible, as this exposes patients to unnecessary complications. 6
• Avoid attempting definitive stone extraction during acute severe cholangitis; focus solely on decompression. 6
• Do not withhold empiric antibiotics to obtain cultures first—administration within 1 hour of septic shock diagnosis is mandatory. 6
• Do not assume standard antibiotic regimens will be effective without cultures, given the 72% rate of resistant organisms. 5