Treatment of Carbapenem-Resistant Klebsiella Pneumoniae Infections
For carbapenem-resistant Klebsiella (CR-Klebsiella) infections, ceftazidime-avibactam is recommended as first-line therapy, with specific regimens based on infection site and severity. 1, 2
First-Line Treatment Options
Preferred Agents (Based on Infection Site)
Bloodstream Infections:
- Ceftazidime-avibactam 2.5 g IV q8h infused over 3 hours (7-14 days) 1
- Alternative options:
- Meropenem-vaborbactam 4 g IV q8h (7-14 days)
- Imipenem-cilastatin-relebactam 1.25 g IV q6h (7-14 days)
Complicated Urinary Tract Infections:
- Ceftazidime-avibactam 2.5 g IV q8h (5-7 days) 1
- Alternative options:
- Meropenem-vaborbactam 4 g IV q8h (5-7 days)
- Imipenem-cilastatin-relebactam 1.25 g IV q6h (5-7 days)
- Aminoglycosides (for susceptible isolates):
- Gentamicin 5-7 mg/kg/day IV QD
- Amikacin 15 mg/kg/day IV QD
- Plazomicin 15 mg/kg IV q12h
Complicated Intra-abdominal Infections:
- Ceftazidime-avibactam 2.5 g q8h + metronidazole 500 mg q6h (5-7 days) 1
- Alternative options:
- Imipenem-cilastatin-relebactam 1.25 g IV q6h (5-7 days)
- Tigecycline 100 mg IV loading dose, then 50 mg IV q12h (5-7 days)
- Eravacycline 1 mg/kg IV q12h (5-7 days)
Combination Therapy Considerations
Combination therapy should be considered for:
- Critically ill patients with septic shock
- High-risk infections (e.g., immunocompromised hosts)
- Severe infections with high bacterial burden
Recommended combinations:
- For severe infections: Ceftazidime-avibactam + aminoglycoside 1, 2
- For colistin-resistant strains: Colistin + rifampicin 3
- For highly resistant strains: Colistin + tigecycline (synergistic against most CR-Klebsiella isolates) 4, 5, 6
Treatment Algorithm
Obtain cultures and antimicrobial susceptibility testing
- Identify specific resistance mechanisms if possible (KPC, NDM, OXA-48, etc.)
Initial empiric therapy while awaiting susceptibility results:
- Ceftazidime-avibactam 2.5 g IV q8h (extended infusion over 3 hours)
- Consider adding a second agent in critically ill patients
Definitive therapy based on susceptibility:
- If susceptible to ceftazidime-avibactam: Continue as monotherapy for stable patients
- If resistant to ceftazidime-avibactam:
- Consider meropenem-vaborbactam or imipenem-relebactam if susceptible
- For pan-resistant strains: Use polymyxin-based combinations (colistin + tigecycline or colistin + rifampicin)
Duration of therapy:
- Bloodstream infections: 10-14 days
- Complicated UTI: 5-7 days
- Complicated intra-abdominal infections: 5-7 days
- Hospital-acquired/ventilator-associated pneumonia: 10-14 days
Special Considerations
High-dose tigecycline regimen (loading dose 200 mg, then 100 mg q12h) should be considered when using tigecycline for bloodstream infections due to its low serum concentrations at standard doses 1, 2
Extended infusion of beta-lactams is strongly recommended to optimize pharmacokinetic/pharmacodynamic parameters 1
Therapeutic drug monitoring is recommended when using polymyxins and aminoglycosides to minimize toxicity while ensuring efficacy 2
Source control (drainage of abscesses, removal of infected devices) is essential for successful treatment 2
Carbapenem-containing combinations may be beneficial when the meropenem MIC is ≤8 mg/L, using high-dose extended infusion (2 g IV q8h infused over 3 hours) 1
Common Pitfalls to Avoid
Monotherapy with tigecycline for bloodstream infections (inadequate serum levels)
Inadequate dosing of polymyxins (colistin requires a loading dose of 5 mg CBA/kg followed by maintenance dosing)
Failure to adjust dosing for renal function, particularly for ceftazidime-avibactam and polymyxins
Delayed source control which significantly impacts mortality regardless of antimicrobial choice
Inadequate duration of therapy, especially for deep-seated infections or immunocompromised hosts
By following this structured approach to the management of carbapenem-resistant Klebsiella infections, clinicians can optimize treatment outcomes while minimizing the emergence of further resistance.