Tigecycline Plus Polymyxin for Abdominal Infections
For carbapenem-resistant Enterobacterales (CRE) intra-abdominal infections, use combination therapy with tigecycline 100 mg IV loading dose followed by 50 mg IV every 12 hours PLUS polymyxin B (colistin) 5 mg CBA/kg IV loading dose, then 2.5 mg CBA × (1.5 × CrCl + 30) IV every 12 hours, particularly in patients with severe sepsis or septic shock. 1
When to Use This Combination
Reserve tigecycline-polymyxin combination specifically for:
- CRE-caused intra-abdominal infections with severe sepsis or septic shock 1
- High mortality risk patients - the INCREMENT cohort demonstrated combination therapy reduced mortality by 44% in patients with high-mortality scores, though not in low-mortality patients 1
- Bloodstream infections secondary to intra-abdominal sources - meta-analysis of 6 studies showed polymyxin-based combinations reduced mortality (39.3% vs 56.4%; OR: 0.52,95% CI 0.33-0.83; p=0.006) 1
Specific Dosing Regimen
- Loading dose: 100 mg IV over 30-60 minutes
- Maintenance: 50 mg IV every 12 hours
- Duration: 5-7 days for intra-abdominal infections, guided by clinical response and source control 1
- Hepatic adjustment: Reduce to 25 mg IV every 12 hours for Child-Pugh C cirrhosis 2
Polymyxin B (colistin) dosing: 1
- Loading dose: 5 mg colistin base activity (CBA)/kg IV
- Maintenance: 2.5 mg CBA × (1.5 × CrCl + 30) IV every 12 hours
- Note: 1 million international units colistin methanesulfonate ≈ 33 mg CBA 1
Alternative Combination Partner
Meropenem can replace polymyxin in the combination if susceptibility testing permits: 1
- Meropenem 1 g IV every 8 hours by extended 3-hour infusion
- Extended infusion is critical if MIC ≥8 mg/L 1
- Selection between polymyxin or meropenem should be based on susceptibility testing results 1
Evidence Supporting Combination Over Monotherapy
Combination therapy demonstrates superior outcomes: 1
- Systematic review showed combination therapy had lower overall mortality versus monotherapy for CR-Klebsiella pneumoniae infections (OR: 1.45; 95% CI 1.18-1.78; p<0.001) 1
- No significant difference between 2-drug versus 3-drug combinations 1
- Tigecycline monotherapy showed comparable outcomes in less severe cases (80.6% vs 73.2% clinical response), but this may reflect indication bias 1
When Monotherapy May Be Acceptable
For non-CRE community-acquired intra-abdominal infections of mild-to-moderate severity: 1
- Tigecycline 100 mg IV loading, then 50 mg IV every 12 hours as monotherapy is appropriate 1
- Real-world European data showed 77.4% clinical response with tigecycline (80.6% for monotherapy specifically) in 785 patients, though outcomes were lower with high disease severity 3
- Duration: 5-14 days based on clinical response 2
Critical Pitfalls to Avoid
Do not use tigecycline monotherapy for bacteremia/bloodstream infections - suboptimal serum concentrations make combination therapy or alternative agents necessary 4
Avoid tigecycline for Pseudomonas aeruginosa or Proteus mirabilis - tigecycline lacks activity against these organisms 1, 5
Do not use polymyxins for routine community-acquired E. coli infections - reserve colistin for carbapenem-resistant organisms due to significant nephrotoxicity 4
Monitor for nephrotoxicity with polymyxin therapy - this is the primary dose-limiting toxicity requiring close renal function monitoring 4
Ensure adequate source control - antimicrobial therapy alone is insufficient without drainage or surgical intervention for intra-abdominal infections 5
Preferred Alternatives for CRE Intra-Abdominal Infections
If available and susceptible, consider these before tigecycline-polymyxin: 1
- Ceftazidime-avibactam 2.5 g IV every 8 hours plus metronidazole 500 mg every 6 hours 1
- Eravacycline 1 mg/kg IV every 12 hours (novel fluorocycline with 94% clinical cure rate in real-world CRE cases) 1
- Imipenem-cilastatin-relebactam 1.25 g IV every 6 hours 1
These newer agents may offer better tolerability profiles than polymyxin-based combinations while maintaining efficacy against CRE 1.