What is the treatment for Klebsiella infections?

Treatment of Klebsiella Infections

For Klebsiella infections, ceftazidime-avibactam is the treatment of choice, especially for multidrug-resistant strains, with antibiotic selection guided by antimicrobial susceptibility testing. 1

Initial Treatment Approach

Antibiotic Selection Based on Severity and Resistance

1. For susceptible Klebsiella strains:

   • Imipenem and cilastatin is FDA-approved for Klebsiella infections in various sites including respiratory tract, urinary tract, intra-abdominal, gynecologic, bloodstream, bone and joint, and skin and skin structure infections 2
   • Third- and fourth-generation cephalosporins, quinolones, or carbapenems are effective options 3

2. For multidrug-resistant Klebsiella (MDR):

   • Ceftazidime-avibactam (2.5g IV q8h) is the first-line therapy 1, 4
   • Alternative options include:
     • Meropenem-vaborbactam (4g IV q8h) 1
     • Imipenem-cilastatin-relebactam (1.25g IV q6h) 1
     • Plazomicin (15 mg/kg IV q12h) for susceptible isolates 1
     • Tigecycline (100mg IV loading dose then 50mg IV q12h) 1

3. For critically ill patients with suspected Klebsiella infection:

   • Combination therapy with two antimicrobial agents of different classes with gram-negative activity is recommended as initial therapy 5
   • De-escalation to a single appropriate antibiotic once culture and susceptibility results are available 5

Monotherapy vs. Combination Therapy

Combination therapy is superior to monotherapy for serious Klebsiella infections:

• Significantly higher treatment failure rates with monotherapy compared to combination therapy (49% vs 25%) 6
• Respiratory infections particularly benefit from combination therapy (67% failure with monotherapy vs 29% with combination) 6
• Polymyxin monotherapy has higher failure rates than polymyxin-based combination therapy (73% vs 29%) 6
• Carbapenem monotherapy has higher failure rates than carbapenem-based combination therapy (60% vs 26%) 6

Treatment Based on Infection Site

1. Bloodstream infections:

   • 10-14 days of appropriate antibiotic therapy 1
   • Remove infected catheters or devices when possible 5

2. Respiratory infections:

   • 7-14 days of antibiotic therapy 1
   • May need extension in immunocompromised patients 1

3. Urinary tract infections:

   • 7-14 days for complicated UTIs 1

4. Intra-abdominal infections:

   • 5-14 days of antibiotic therapy 1
   • For complicated intra-abdominal infections, ceftazidime-avibactam plus metronidazole has shown effectiveness against Klebsiella oxytoca with clinical cure rates of 77.8% 4

5. Endocarditis:

   • Prolonged course (6+ weeks) of combined antibiotic therapy, often with surgical intervention 1

Special Considerations

Carbapenem-Resistant Klebsiella

For carbapenem-resistant Klebsiella pneumoniae (CRKP):

• Carbapenems may still be effective against isolates with MICs ≤4 mg/L, especially when administered in combination with another active antibiotic 7
• High-dose/prolonged-infusion regimen of a carbapenem may be effective for isolates with MICs up to 4 mg/L 7
• For highly resistant strains, ceftazidime-avibactam is the preferred treatment 1, 8

Monitoring and Follow-up

• Antimicrobial susceptibility testing is essential to guide appropriate antibiotic selection 1
• Molecular characterization of resistance mechanisms should be performed when available 1
• Infectious disease consultation is highly recommended for all MDR Klebsiella pneumoniae infections 1

Common Pitfalls to Avoid

1. Misidentification by routine testing:

   • KPC-producing bacteria are often misidentified by routine microbiological susceptibility testing 9
   • Resistance to ertapenem is a better indicator of KPC presence 9

2. Underestimating resistance:

   • Delaying appropriate antimicrobial therapy increases mortality 1
   • Overuse of carbapenems contributes to increasing resistance 1

3. Inadequate source control:

   • Drainage of infection focus is necessary in addition to antibiotic therapy 1
   • Device removal is essential when infections involve medical devices 5

4. Inappropriate dosing:

   • Dose modification according to renal function is necessary to prevent treatment failure and development of resistance 1
   • Prolonged infusion of β-lactam antibiotics should be considered for pathogens with high MICs 1

By following these evidence-based recommendations and considering the specific characteristics of the infection and patient, clinicians can optimize treatment outcomes for Klebsiella infections while minimizing the risk of further antimicrobial resistance development.