What is the best treatment approach for empyema thoracis caused by panresistant Klebsiella pneumoniae?

Management of Empyema Thoracis with Panresistant Klebsiella pneumoniae

For empyema thoracis caused by panresistant Klebsiella pneumoniae, the recommended treatment approach is intravenous polymyxins (colistin or polymyxin B) combined with adjunctive inhaled colistin, along with appropriate surgical drainage procedures. 1

Initial Management

• Surgical debridement and drainage of the empyema is the mainstay of therapy and should be performed whenever feasible 1
• Intercostal chest tube drainage is essential for effective source control 2
• Infectious disease consultation is highly recommended for management of infections caused by multidrug-resistant organisms 1

Antimicrobial Therapy

Primary Regimen

• Intravenous polymyxins (colistin or polymyxin B) as the backbone of therapy for carbapenem-resistant pathogens that are sensitive only to polymyxins 1
• Adjunctive inhaled colistin to improve clinical outcomes by achieving higher drug concentrations at the infection site 1
• Therapeutic drug monitoring (TDM) should be performed whenever possible when using polymyxins to optimize dosing and minimize toxicity 1

Combination Therapy Options

• For patients in septic shock or at high risk of death, combination therapy with multiple active agents is recommended 1
• Consider adding one of the following to polymyxin therapy based on synergy testing:
  • Fosfomycin (if available and susceptibility is confirmed) 1
  • Rifampicin (shows synergistic activity against colistin-resistant KPC-producing K. pneumoniae in vitro) 3
  • High-dose tigecycline (200 mg loading dose followed by 100 mg every 12 hours) may be considered as part of combination therapy, though not as monotherapy 4, 5

Important Considerations

• Tigecycline should not be used as monotherapy for respiratory infections due to increased mortality risk 5
• Tigecycline is not indicated for hospital-acquired pneumonia or ventilator-associated pneumonia per FDA labeling 5
• Colistin-tigecycline combinations have shown synergistic activity against ESBL-producing K. pneumoniae with carbapenem resistance 6
• Prolonged infusion of β-lactams (if any susceptibility remains) is recommended for pathogens with high MICs 1

Duration of Therapy

• For empyema thoracis, a minimum of 2-4 weeks of antimicrobial therapy is typically required, though duration should be individualized based on clinical response 1
• Continue therapy until clinical, radiological, and laboratory parameters show significant improvement 1

Monitoring and Follow-up

• Regular monitoring of renal function is essential when using polymyxins due to nephrotoxicity risk 1
• Serial imaging to assess resolution of the empyema collection 2
• Additional drainage procedures may be necessary if there is inadequate clinical response 2

Surgical Management Options

• Consider early surgical consultation for:
  • Decortication if there is significant pleural thickening or loculations 2
  • Video-assisted thoracoscopic surgery (VATS) for multiloculated empyemas 2
  • Open thoracotomy for cases refractory to less invasive approaches 2

Caveats and Pitfalls

• Hypokalemia is a common adverse effect of intravenous fosfomycin and polymyxin therapy and requires close monitoring 1
• Nephrotoxicity is a major concern with polymyxin therapy; dose adjustment is necessary in renal impairment 1
• Resistance to polymyxins can develop during therapy, necessitating repeat cultures and susceptibility testing 3
• The evidence for specific combination regimens against panresistant K. pneumoniae is limited and largely based on in vitro studies and case reports rather than randomized controlled trials 1