What antibiotics should be given to a post-operative patient with fever on day 1 following a cholecystectomy (gallbladder removal), where the source of infection is unknown?

Antibiotic Management for Post-Cholecystectomy Day 1 Fever

For a patient with fever on post-operative day 1 after cholecystectomy with unknown infection source, you should immediately investigate for complications (bile leak, biloma, or bile peritonitis) and initiate broad-spectrum antibiotics empirically while pursuing source control, as uncomplicated cholecystectomy patients should have antibiotics discontinued within 24 hours unless infection outside the gallbladder wall is identified. 1

Immediate Assessment Required

Before committing to extended antibiotic therapy, you must determine if this represents:

• Complicated post-operative infection (bile leak, biloma, bile peritonitis, bile duct injury)
• Simple post-operative fever (atelectasis, inflammatory response)
• Spilled gallstones (can present as fever of unknown origin weeks after surgery) 2

Obtain imaging immediately: Triphasic CT scan is first-line to detect intra-abdominal fluid collections and ductal dilation, potentially complemented with CE-MRCP for exact visualization of bile duct injury 3

Check liver function tests: Direct and indirect bilirubin, AST, ALT, ALP, GGT, albumin, plus CRP, PCT, and lactate to evaluate severity of acute inflammation and sepsis 3

Antibiotic Decision Algorithm

If Uncomplicated Cholecystectomy (No Evidence of Bile Leak or Collections)

Discontinue antibiotics within 24 hours post-operatively 1, 4

• Multiple randomized trials demonstrate no benefit of post-operative antibiotics for uncomplicated cholecystitis 3, 5, 6, 7
• Fever alone on POD#1 does not mandate continued antibiotics without identified source 1

If Complicated Infection Identified (Bile Leak, Biloma, Bile Peritonitis)

Start broad-spectrum antibiotics immediately (within 1 hour): 3

First-line options:

• Piperacillin/tazobactam 3.375g IV q6h (or 4.5g IV q6h for severe infection) 3, 8
• Meropenem 3
• Imipenem/cilastatin 3
• Ertapenem 3

Add amikacin if patient is in shock 3

Add fluconazole in fragile patients or cases of delayed diagnosis 3

If Previous Biliary Infection or Preoperative Biliary Drainage

Use 4th-generation cephalosporins as broad-spectrum coverage, with adjustments based on culture results 3

• Patients with preoperative cholecystitis, cholangitis, or endoscopic stenting/PTBD are at higher risk for local and systemic sepsis 3

If Suspected Bile Duct Injury Without Previous Infection

Broad-spectrum antibiotics may be considered (weak recommendation, very low quality evidence) 3

Critical Pitfalls to Avoid

Do not continue antibiotics beyond 24 hours without identifying a specific infectious source 1, 4

• The most common error is reflexively continuing antibiotics for low-grade fever without documented infection

Do not delay imaging in a febrile post-cholecystectomy patient 3

• Bile leaks and collections require source control, not just antibiotics
• CT scan should be obtained urgently to rule out surgical complications

Consider healthcare-associated pathogens if patient came from nursing home or has recent healthcare exposure 3

• May require anti-enterococcal coverage and consideration of multidrug-resistant organisms

Remember that elderly patients and those with biliary-enteric anastomosis may require anaerobic coverage 1

Duration of Therapy

• Uncomplicated cholecystitis: Maximum 24 hours post-operatively 1, 4
• Severe (Tokyo Grade III) cholecystitis: Maximum 4 days, potentially shorter 4
• Bile leak with source control: Adjust based on clinical response and culture results 3

Source Control Priority

Antibiotics are adjunctive to source control 3

• Percutaneous drainage of collections is mandatory if present 3
• ERCP with sphincterotomy and stent placement for persistent bile leaks 3
• Surgical re-exploration may be necessary for major bile duct injuries 3