What antibiotic regimen should be used for a patient with choledocholithiasis undergoing endoscopic retrograde cholangiopancreatography, both for prophylaxis when there is no cholangitis and for treatment if acute cholangitis is present?

Antibiotic Coverage for Choledocholithiasis

For choledocholithiasis without cholangitis, prophylactic antibiotics are mandatory only when performing ERCP, using amoxicillin/clavulanate 2g/0.2g IV every 8 hours for non-critically ill patients; when acute cholangitis is present, start antibiotics immediately with the same regimen for moderate disease or escalate to piperacillin/tazobactam 4g/0.5g IV every 6 hours for critically ill patients, continuing for 3-5 days after successful biliary drainage. 1

Prophylaxis for ERCP Without Cholangitis

When Prophylaxis is Required

• ERCP must always be performed under antibiotic cover in patients with choledocholithiasis, as prophylaxis reduces septic complications by approximately 80% in patients with incomplete biliary drainage. 1, 2
• Prophylactic antibiotics are particularly critical when biliary obstruction is present, as failure to achieve complete drainage is the most important predictor of bacteremia. 2, 3

Recommended Prophylactic Regimen

• Amoxicillin/clavulanate 2g/0.2g IV every 8 hours is the appropriate first-line prophylactic regimen for immunocompetent patients undergoing ERCP. 1
• Alternative effective agents include piperacillin 4g IV, cefazolin, cefuroxime, cefotaxime, or ciprofloxacin. 3
• Start antibiotics just before the ERCP procedure. 4

Duration of Prophylaxis

• Continue prophylaxis until biliary drainage is completely unobstructed, with a maximum duration of 7 days if multiple procedures are needed. 4
• If complete drainage is achieved during the initial ERCP, discontinue antibiotics within 24 hours post-procedure. 5

Treatment When Acute Cholangitis is Present

Immediate Antibiotic Initiation

• Antibiotics are mandatory and must be started immediately upon diagnosis of acute cholangitis, as delays significantly increase morbidity and mortality. 1, 6
• Empiric therapy should target Enterobacteriaceae, particularly Escherichia coli, which is the predominant pathogen (68% of isolates are gram-negative bacteria). 7, 3

Antibiotic Selection Based on Severity

For Non-Critically Ill Patients (Class A/B):

• Amoxicillin/clavulanate 2g/0.2g IV every 8 hours is the recommended first-line regimen. 1
• Alternative monotherapy options include piperacillin/tazobactam 4g/0.5g IV every 6 hours or cefoperazone/sulbactam, which show 85-89% susceptibility against bile pathogens. 7

For Critically Ill Patients (Class C):

• Piperacillin/tazobactam 4g/0.5g IV every 6 hours or 16g/2g by continuous infusion is recommended as first-line therapy. 1
• For septic shock, escalate to meropenem 1g IV every 6 hours by extended infusion or continuous infusion. 1
• Imipenem shows 97.9% susceptibility and should be reserved as a backup antibiotic for resistant organisms. 7

Coverage Considerations

• Enterococcal coverage is NOT routinely required for community-acquired biliary infections in immunocompetent patients, as enterococcal pathogenicity remains unclear. 5, 3
• Add ampicillin or vancomycin for enterococcal coverage only in immunocompromised patients, those with prior cephalosporin exposure, or patients with valvular heart disease. 5
• Anaerobic coverage is NOT required unless a biliary-enteric anastomosis is present, the patient is elderly, or in serious clinical condition. 5, 3

Duration of Antibiotic Therapy

Standard Duration After Biliary Drainage

• 3-5 days of antibiotics after adequate biliary decompression via ERCP is the recommended duration for patients with Class A or B cholangitis. 1, 8
• For immunocompetent, non-critically ill patients, 4 days of therapy is sufficient if adequate source control is achieved. 1
• For immunocompromised or critically ill patients, extend therapy to 7 days based on clinical condition and inflammatory markers. 1

Special Circumstances Requiring Prolonged Therapy

• Extend treatment to 2 weeks if Enterococcus or Streptococcus are isolated to prevent infectious endocarditis. 8
• For biloma or generalized peritonitis, consider 5-7 days of treatment. 8
• Patients with ongoing signs of infection beyond 7 days warrant diagnostic investigation for inadequate source control. 1

Timing of Biliary Drainage

Urgency Based on Clinical Presentation

• Urgent ERCP within 24 hours is required for patients with cholangitis, as delayed drainage is associated with 45.5% mortality at 30 days compared to 13% with early drainage. 1, 6
• Early ERCP within 72 hours should be performed for high suspicion of persistent common bile duct stones even without cholangitis. 1
• Continue antibiotics throughout the waiting period if cholangitis is present. 1

Definitive Management with Cholecystectomy

Timing of Surgery

• Perform laparoscopic cholecystectomy during the same hospital admission after ERCP once the patient has recovered and laboratory values have normalized. 1
• If same-admission cholecystectomy is not feasible, schedule within 2-4 weeks after discharge to prevent recurrent biliary events. 1

Post-Cholecystectomy Antibiotics

• Routine post-operative antibiotics are NOT recommended after successful cholecystectomy for mild to moderate disease. 1
• For complicated acute cholecystitis, short-course postoperative therapy of 1-4 days is appropriate. 1

Critical Pitfalls to Avoid

• Do not delay ERCP in patients with cholangitis beyond 24 hours, as this dramatically increases mortality from 13% to 45.5%. 1, 6
• Do not perform ERCP without antibiotic coverage in patients with suspected or confirmed cholangitis or biliary obstruction. 1
• Do not continue broad-spectrum antibiotics after adequate source control is achieved, as this promotes antibiotic resistance without improving outcomes. 1, 8
• Do not delay cholecystectomy beyond 2-4 weeks after ERCP, as this dramatically increases recurrent biliary event rates. 1
• Do not routinely cover enterococci in community-acquired infections in immunocompetent patients, as this is unnecessary and promotes resistance. 5, 3
• Do not use aminoglycosides for more than a few days during cholestasis, as the risk of nephrotoxicity is significantly increased. 3