Treatment of Carbapenem-Resistant E. coli in Post-Surgical Intra-Abdominal Infection
For a patient with suspected carbapenem-resistant (CR) E. coli intra-abdominal infection following jejunostomy, initiate ceftazidime-avibactam 2.5 g IV every 8 hours (infused over 3 hours) plus metronidazole 500 mg IV every 6 hours immediately, pending culture and susceptibility results. 1, 2
First-Line Empiric Therapy Algorithm
Immediate empiric treatment selection:
Ceftazidime-avibactam 2.5 g IV q8h (infused over 3 hours) + metronidazole is the preferred first-line agent for suspected carbapenem-resistant Enterobacterales (CRE) complicated intra-abdominal infections (cIAI), as it provides coverage against KPC and OXA-48 carbapenemase producers while preserving activity against E. coli 2, 1
This regimen demonstrated 81.6% clinical cure rates in cIAI trials and specifically showed 80.4% cure rates for E. coli infections 3
Alternative first-line options if ceftazidime-avibactam is unavailable: imipenem-cilastatin-relebactam 1.25 g IV q6h plus metronidazole 2
Critical Decision Points Based on Susceptibility Results
Once cultures return, adjust therapy based on these specific scenarios:
If KPC or OXA-48 Producer (Non-MBL):
- Continue ceftazidime-avibactam monotherapy (with metronidazole for anaerobic coverage) if susceptible 1
- Meropenem-vaborbactam 4 g IV q8h is an equally effective alternative for KPC producers 1, 4
If Metallo-β-lactamase (MBL) Producer:
- Switch to cefiderocol or aztreonam plus ceftazidime-avibactam combination 1
- Ceftazidime-avibactam alone is ineffective against MBL producers 5
If Susceptible to Older Agents:
- Polymyxin-based combination therapy: colistin 5 mg CBA/kg IV loading dose, then 2.5 mg CBA × (1.5 × CrCl + 30) IV q12h PLUS either tigecycline 100 mg IV loading then 50 mg IV q12h OR meropenem 1 g IV q8h by extended infusion 2
- Tigecycline 100 mg IV loading, then 50 mg IV q12h plus metronidazole is an alternative, though it performs poorly in bacteremic patients 2
Duration and Monitoring
Treatment duration: 5-7 days for source-controlled cIAI 2
- Extend to 7-14 days if inadequate source control or persistent signs of infection 2
- Obtain intra-operative cultures immediately to guide de-escalation or expansion of therapy 2
- Perform antimicrobial susceptibility testing (AST) on all isolates to guide targeted therapy 2
Critical Pitfalls to Avoid
Never use monotherapy with the following agents for severe CRE infections:
- Polymyxins alone - always combine with at least one other active agent 1
- Tigecycline alone - associated with treatment failure in bacteremia and has poor plasma concentrations 2, 1
- Aminoglycosides alone - only acceptable as monotherapy for uncomplicated urinary tract infections 2
Avoid carbapenem monotherapy for documented CRE unless using high-dose extended-infusion regimens (meropenem 1 g IV q8h infused over 3 hours) with MIC ≤8 mg/L as part of combination therapy 1
Do not add unnecessary combination therapy to newer β-lactam/β-lactamase inhibitors (ceftazidime-avibactam, meropenem-vaborbactam) when the organism is susceptible - this provides no benefit and increases toxicity 1
Special Considerations for This Patient
Diabetes-specific factors:
- Type 2 diabetes increases risk of MDR infections and is associated with higher rates of carbapenemase-producing organisms in surgical site infections 6
- Recent surgery (exploratory laparotomy with jejunostomy) represents healthcare-associated infection with high risk for MDR pathogens 2
Risk factors present that justify empiric CRE coverage:
- Recent abdominal surgery (healthcare-associated infection) 2
- Likely prior antibiotic exposure perioperatively 2
- Post-surgical intra-abdominal infection setting where CRE prevalence is increasing 2
Infectious disease consultation is strongly recommended for all MDRO infections to optimize outcomes 2
Prolonged infusion of β-lactams (infusing over 3 hours rather than standard 30-60 minutes) is recommended for pathogens with high MIC values to maximize time above MIC 2