What can be given along with colistin for a Klebsiella infection sensitive to colistin and tigecycline?

Treatment for Klebsiella Infection Sensitive Only to Colistin and Tigecycline

For Klebsiella infections sensitive only to colistin and tigecycline, the optimal treatment is colistin plus high-dose tigecycline in combination therapy. 1

Rationale for Combination Therapy

Combination therapy is strongly recommended for multidrug-resistant Klebsiella infections, particularly when treatment options are limited. The evidence supports several key points:

• Colistin-based combination therapy shows significantly lower 30-day mortality compared to colistin monotherapy (35.7% vs 55.5%) 1
• Tigecycline monotherapy is associated with higher mortality compared to tigecycline-based combination therapy 1
• Colistin plus tigecycline demonstrates synergistic activity against resistant Klebsiella strains 2, 3

Recommended Dosing Regimen

Colistin:

• Loading dose: 5 mg colistin base activity (CBA)/kg IV
• Maintenance: 2.5 mg CBA × (1.5 × CrCl + 30) IV q12h 1
• For patients with normal renal function: loading dose of 9 million IU followed by 4.5 million IU every 12 hours 1

Tigecycline:

• High-dose regimen: 200 mg IV loading dose, followed by 100 mg IV every 12 hours 1
• Standard dosing (100 mg loading dose followed by 50 mg every 12 hours) is inadequate for bloodstream infections due to low serum concentrations 1, 4

Special Considerations

1. Site of infection matters:

   • For bloodstream infections: Treatment duration of 10-14 days 1
   • For pneumonia: Tigecycline monotherapy is not recommended; combination therapy is essential 1

2. Limitations of tigecycline:

   • Low serum and urinary concentrations limit its effectiveness as monotherapy for bacteremia and urinary tract infections 1
   • FDA warning for increased all-cause mortality with tigecycline (0.6% higher than comparators) 4

3. Alternative combinations to consider:

   • If aminoglycosides show any activity (even intermediate): Consider adding gentamicin to the regimen 5, 6
   • For KPC-producing strains: Colistin plus rifampicin has shown synergistic activity 7

4. Monitoring recommendations:

   • Regular renal function monitoring for colistin toxicity
   • Therapeutic drug monitoring for colistin when available
   • Clinical response assessment within 72 hours to determine effectiveness

Evidence for Synergy

Time-kill studies have demonstrated that colistin plus tigecycline combinations show:

• Synergistic activity in 8/9 isolates of ESBL-producing Klebsiella pneumoniae 2
• Bactericidal activity against most KPC-producing strains when used in combination 3
• Prevention of regrowth that occurs when colistin is used alone 8

Pitfalls to Avoid

1. Avoid tigecycline monotherapy for bloodstream infections due to inadequate serum concentrations and higher mortality rates 1

2. Don't underdose colistin - inadequate dosing leads to suboptimal plasma concentrations and treatment failure 1

3. Don't delay therapy - prompt initiation of appropriate combination therapy is essential for improved outcomes

4. Don't forget to adjust doses for renal impairment with colistin (but not for tigecycline in hepatic impairment unless severe) 1, 4

5. Don't continue ineffective therapy - reassess clinical response within 72 hours and consider alternative approaches if no improvement

By following these evidence-based recommendations, you can optimize treatment outcomes for patients with highly resistant Klebsiella infections limited to colistin and tigecycline susceptibility.