What antibiotic prophylaxis is recommended for patients with Carbapenem-Resistant Enterobacteriaceae (CRE) colonization or infection undergoing Endoscopic Retrograde Cholangiopancreatography (ERCP)?

Antibiotic Prophylaxis for CRE Colonization/Infection Before ERCP

For patients with known CRE colonization or infection undergoing ERCP, targeted antibiotic prophylaxis based on susceptibility testing is essential, with preferred regimens including ceftazidime-avibactam, meropenem-vaborbactam, or aminoglycoside-based combinations depending on the resistance profile and infection severity. 1

Risk Assessment and Screening Considerations

• CRE carriers undergoing invasive procedures face substantially elevated infection risk compared to non-carriers, with postoperative infection rates ranging from 22-45% in colonized patients versus 2-5% in non-colonized patients 1
• Standard ERCP prophylaxis recommendations (fluoroquinolones, cephalosporins, or gentamicin) are inadequate for CRE carriers since these organisms are resistant to these agents 2, 3
• Biliary obstruction with incomplete drainage after ERCP carries up to 18% infection risk, making prophylaxis critical in this population 4, 5

Recommended Prophylactic Regimens for CRE Carriers

First-Line Options (Based on Susceptibility)

For CRE susceptible to newer beta-lactam/beta-lactamase inhibitors:

• Ceftazidime-avibactam 2.5 g IV over 3 hours is the preferred agent if the isolate is susceptible, given 30-60 minutes before the procedure 1
• Meropenem-vaborbactam 4 g IV is an alternative first-line option for susceptible CRE 1
• These newer agents should be used as monotherapy without combination therapy for prophylaxis 1

For CRE with metallo-beta-lactamases or resistance to standard agents:

• Aztreonam plus ceftazidime-avibactam combination is recommended for metallo-beta-lactamase producers 1
• Cefiderocol may be considered for extensively resistant CRE, though evidence is limited for prophylactic use 1

Alternative Regimens When Newer Agents Unavailable

Aminoglycoside-based prophylaxis:

• Gentamicin 5 mg/kg IV single dose or amikacin can be used if the isolate is susceptible 1
• Avoid aminoglycosides in patients with renal dysfunction or when combined with other nephrotoxic drugs 1
• Consider adding anaerobic coverage (metronidazole) for biliary procedures 2, 3

Polymyxin-based regimens:

• Reserved for CRE susceptible only to polymyxins when no other options exist 1
• Should be combined with another active agent when possible 1

Timing and Administration

• Administer prophylaxis 30-60 minutes before the procedure (120 minutes for vancomycin if needed for Gram-positive coverage) 1
• Single-dose prophylaxis is generally sufficient unless incomplete biliary drainage occurs 4, 5
• If biliary obstruction persists after ERCP or drainage is incomplete, continue antibiotics for 24-48 hours post-procedure to prevent cholangitis 4, 5

Critical Pitfalls to Avoid

Do not use standard ERCP prophylaxis regimens in CRE carriers:

• Fluoroquinolones (ciprofloxacin) are ineffective due to co-resistance 2, 3
• Standard cephalosporins (cefoxitin, ceftriaxone) will not cover CRE 6, 4
• Carbapenems alone (ertapenem, meropenem) are ineffective for carbapenem-resistant organisms 1

Antimicrobial stewardship considerations:

• Obtain pre-procedure rectal surveillance cultures if CRE colonization status is unknown in high-risk patients 1
• Reserve broad-spectrum agents (ceftazidime-avibactam, meropenem-vaborbactam) for documented CRE rather than empiric use 1
• Document susceptibility testing results to guide targeted prophylaxis 1

Special Populations

For patients with incomplete biliary drainage anticipated:

• Plan for therapeutic rather than prophylactic antibiotic course (7-14 days) 6, 5
• Ensure adequate biliary decompression to prevent cholangitis regardless of antibiotics 4, 5

For immunosuppressed or neutropenic patients:

• Consider combination therapy even for prophylaxis given higher infection risk 2, 3
• Add metronidazole for anaerobic coverage in neutropenic patients 2, 3

For patients with endocarditis risk:

• Add Gram-positive coverage (amoxicillin or vancomycin) to the CRE-directed regimen 2, 3