What is the management for a patient with a pan-resistant Klebsiella (Klebsiella pneumoniae) infection?

Management of Pan-Resistant Klebsiella pneumoniae Infections

For pan-resistant Klebsiella pneumoniae infections, treatment with combination therapy using multiple active agents is strongly recommended, particularly combining newer β-lactam/β-lactamase inhibitors (when available) or using combination regimens with colistin, high-dose tigecycline, and carbapenems for severe infections. 1, 2

First-Line Treatment Options

• Ceftazidime/avibactam or meropenem/vaborbactam should be used as first-line treatments for KPC-producing Klebsiella pneumoniae when available, as they demonstrate superior clinical outcomes compared to traditional regimens 2
• Imipenem/relebactam and cefiderocol are recommended alternatives when first-line agents are unavailable 2
• For severe infections where the organism is only susceptible to polymyxins, aminoglycosides, tigecycline, or fosfomycin, use more than one drug active in vitro 1

Combination Therapy Approaches

• For pan-resistant isolates, combination therapy with multiple agents is crucial for clinical success 1, 3
• High-dose tigecycline plus colistin has shown success in treating pan-resistant K. pneumoniae bacteremia and pneumonia 3
• Double carbapenem therapy (meropenem plus imipenem) combined with colistin has demonstrated synergistic and bactericidal effects against pandrug-resistant K. pneumoniae 4
• Consider adding amikacin to carbapenem combinations when the isolate shows any degree of susceptibility 5

Dosing Considerations

• Use high-dose extended-infusion meropenem (when MIC ≤8 mg/L) as part of combination therapy 1
• Implement therapeutic drug monitoring (TDM) for polymyxins, aminoglycosides, and carbapenems to optimize dosing and minimize toxicity 1
• For colistin, ensure appropriate dosing based on renal function and monitor for nephrotoxicity 6
• When using tigecycline, consider higher-than-standard dosing (100 mg initial dose, then 50 mg every 12 hours) for severe infections 1

Infection Control Measures

• Place all patients with pan-resistant K. pneumoniae on contact precautions 1
• Perform active surveillance cultures of patients with epidemiologic links to persons from whom pan-resistant organisms have been recovered 1
• In areas with endemic CRE, implement additional strategies including:
  • Point prevalence surveys in high-risk units 1
  • Enhanced compliance with hand hygiene and contact precautions 1
  • Patient cohorting and dedicated staff when possible 1
  • Weekly surveillance cultures until no new cases are identified during outbreaks 1

Special Considerations

• Optimal source control is essential and should always be prioritized to improve outcomes 2
• For non-severe infections, monotherapy with the most active in vitro agent may be considered on an individual basis according to the infection source 1
• Avoid carbapenem-based combination therapy unless the meropenem MIC is ≤8 mg/L 1
• Consider fosfomycin as part of combination therapy when the isolate is susceptible or when synergy has been demonstrated 1

Clinical Pitfalls and Caveats

• Pan-resistant K. pneumoniae infections are associated with high mortality rates, particularly in critically ill patients and those with invasive devices 1, 7
• Patients may remain colonized with pan-resistant isolates even after successful treatment of the acute infection 3
• Unrecognized colonization can serve as a reservoir for transmission during healthcare-associated outbreaks 1
• Mortality is highest in patients with severe infections treated with monotherapy using older agents (polymyxins, aminoglycosides, or tigecycline alone) 1, 2
• The effectiveness of combination therapy appears most pronounced in patients with more severe disease and higher risk of death 1