What is the recommended treatment for MDRO (Multidrug-Resistant Organism) sepsis due to KPC (Klebsiella pneumoniae carbapenemase) Klebsiella?

Treatment of MDRO Sepsis due to KPC Klebsiella

For MDRO sepsis due to KPC Klebsiella pneumoniae, ceftazidime-avibactam 2.5g IV q8h is recommended as the first-line treatment option, with potential combination therapy based on susceptibility testing. 1

First-line Treatment Options

Preferred Regimens

• Ceftazidime-avibactam 2.5g IV q8h (infused over 3 hours) 1
  • Strong recommendation for KPC-producing CRE
  • Demonstrated superior clinical outcomes compared to traditional regimens
  • Lower mortality rates (18.3% vs 40.8%) compared to other active agents 1
  • Consider renal dose adjustments as needed

Alternative First-line Options

• Meropenem-vaborbactam 4g IV q8h 1
• Imipenem-cilastatin-relebactam 1.25g IV q6h 1
• Cefiderocol (for specific susceptible strains) 1

Combination Therapy Considerations

Evidence suggests combination therapy is superior to monotherapy for KPC-producing Klebsiella pneumoniae sepsis, with significantly lower mortality rates (13.3% vs 57.8%) 2.

Recommended Combinations:

1. For KPC-producing strains with limited options:

   • Polymyxin-based combinations (colistin + carbapenem or tigecycline) 1
   • Tigecycline-based combinations 1
   • Ceftazidime-avibactam + fosfomycin (if susceptible) 1

2. For MBL-producing strains:

   • Ceftazidime-avibactam + aztreonam (significantly lower 30-day mortality, HR 0.37) 1

Treatment Algorithm

1. Initial empiric therapy:

   • Start ceftazidime-avibactam 2.5g IV q8h while awaiting susceptibility results
   • Consider adding a second agent based on local resistance patterns

2. After susceptibility results:

   • If susceptible to ceftazidime-avibactam: Continue as monotherapy or consider combination therapy for severe infections
   • If resistant to ceftazidime-avibactam:
     • Switch to meropenem-vaborbactam or imipenem-relebactam if susceptible
     • For pan-resistant strains: Use polymyxin-based combination therapy

3. Duration:

   • 7-14 days total therapy based on clinical response
   • Longer duration may be needed for complicated infections

Special Considerations

• Therapeutic Drug Monitoring (TDM): Perform TDM whenever possible for polymyxins, aminoglycosides, or carbapenems to optimize dosing and reduce toxicity 1

• High-dose extended infusion: For carbapenems, consider extended infusion (3 hours) to optimize pharmacokinetics/pharmacodynamics 1

• Infectious disease consultation: Highly recommended for management of MDRO infections 1

Common Pitfalls to Avoid

1. Monotherapy with traditional agents: Monotherapy with colistin/polymyxin B or tigecycline is associated with higher mortality (66.7%) despite in vitro susceptibility 2

2. Inadequate dosing: Suboptimal dosing, especially with polymyxins and tigecycline, can lead to treatment failure 1

3. Relying solely on routine susceptibility testing: KPC-producing bacteria are often misidentified by routine testing and incorrectly reported as sensitive to carbapenems 3

4. Delayed effective therapy: Time from blood culture collection to start of active antibiotic therapy significantly influences outcomes 1

5. Ignoring source control: Ensure adequate source control measures are implemented alongside antimicrobial therapy

By following this evidence-based approach with newer agents like ceftazidime-avibactam as first-line therapy, potentially in combination with other active agents, outcomes for patients with MDRO sepsis due to KPC Klebsiella can be significantly improved.