Treatment of Acinetobacter Bacteremia Sensitive Only to Tigecycline
Primary Recommendation
Tigecycline should NOT be used as monotherapy for Acinetobacter bacteremia, even when it is the only agent showing in vitro susceptibility. 1 Instead, consider combination therapy with tigecycline PLUS colistin (polymyxin) or another agent, even if the isolate appears resistant to the second agent in vitro, as synergy may occur in vivo. 1, 2
Critical Evidence Against Tigecycline Monotherapy for Bacteremia
Guideline Recommendations
- The IDSA/ATS 2016 guidelines explicitly recommend AGAINST tigecycline for Acinetobacter pneumonia, which has important implications for bacteremia given similar pharmacokinetic limitations. 1
- The FDA label does NOT include bacteremia as an approved indication for tigecycline, limiting approval to complicated skin/soft tissue infections, intra-abdominal infections, and community-acquired pneumonia. 3
Pharmacokinetic Limitations
- Tigecycline achieves extremely low serum concentrations (Cmax only 0.87 mg/L with standard dosing), making it poorly suited for bloodstream infections. 4, 5
- The drug has excellent tissue penetration but poor serum levels, which is the opposite of what is needed for bacteremia. 4
Clinical Outcome Data
- A study of 17 patients with Acinetobacter bacteremia treated with tigecycline showed a 14-day mortality rate of 41.2%, significantly higher than the 13.8% mortality with other appropriate antimicrobials (P = 0.018). 6
- Another study demonstrated that tigecycline-treated Acinetobacter bacteremia had 36.4% mortality versus 14.2% with other antibiotics (P = 0.028). 7
- For isolates with tigecycline MIC of 2 μg/mL, mortality reached 63.6% compared to 14.2% with other agents (P = 0.001). 7
- A case series showed only 28% clinical success rate and 44% microbiologic cure rate with tigecycline for Acinetobacter infections. 8
Recommended Treatment Algorithm
Step 1: Verify Susceptibility Testing
- Confirm tigecycline MIC is ≤1 mg/L (preferably <1 mg/L), as outcomes are particularly poor when MIC = 2 mg/L. 1, 7
- Retest for colistin/polymyxin susceptibility, as this should be the backbone of therapy. 1, 2
Step 2: Implement Combination Therapy
- Primary regimen: IV colistin or polymyxin B PLUS high-dose tigecycline (200 mg loading dose, then 100 mg IV every 12 hours). 1, 4, 2
- The high-dose tigecycline regimen achieves 85% cure rates versus 69.6% with standard dosing for severe infections. 1, 4
- Consider adding sulbactam (6-9 g/day IV in 3-4 divided doses) as a third agent if available and patient can tolerate triple therapy. 2
Step 3: Duration and Monitoring
- Treat for 10-14 days for bacteremia. 2
- Monitor closely for clinical response within 48-72 hours; if no improvement, consider infectious disease consultation for alternative strategies. 2
- Monitor for nephrotoxicity from colistin and for superinfection (occurs in 29.6% of tigecycline-treated patients, often with Pseudomonas). 9, 10
Important Clinical Caveats
When Colistin is Truly Not Available
- If colistin/polymyxin is genuinely unavailable or contraindicated due to severe renal failure, consider:
Factors Associated with Treatment Failure
- Septic shock at presentation increases mortality risk regardless of antibiotic choice. 6
- End-stage renal disease and congestive heart failure are associated with worse outcomes. 6
- Standard-dose tigecycline (50 mg q12h) should never be used for bacteremia—only high-dose regimens have acceptable outcomes. 1, 4
Superinfection Risk
- Pseudomonas aeruginosa causes 46.9% of superinfections in tigecycline-treated patients. 9
- Consider adding anti-pseudomonal coverage if clinical deterioration occurs after initial improvement. 9