What are the considerations for using polymixin B (Polymyxin B), tigecycline, and levofloxacin (Levofloxacin) in the same patient?

Considerations for Using Polymyxin B, Tigecycline, and Levofloxacin in the Same Patient

When considering combination therapy with polymyxin B, tigecycline, and levofloxacin in the same patient, this regimen should generally be avoided due to overlapping toxicities and lack of proven benefit over more targeted combinations for multidrug-resistant infections.

Indications and Rationale

• This combination is typically considered for multidrug-resistant (MDR) Gram-negative infections, particularly carbapenem-resistant Enterobacterales (CRE) or carbapenem-resistant Acinetobacter baumannii (CRAB) 1
• For severe infections caused by CRE susceptible only to polymyxins, aminoglycosides, tigecycline or fosfomycin, combination therapy with more than one active agent is suggested, though specific combinations cannot be definitively recommended 1
• For non-severe CRE infections, monotherapy with an in vitro active old drug is recommended as good clinical practice 1

Efficacy Concerns

• Tigecycline is not recommended for bloodstream infections (BSI) and hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) due to poor outcomes 1
• If tigecycline must be used for pneumonia, high-dose regimens should be considered 1
• Polymyxin B/tigecycline combination therapy has not demonstrated superiority over polymyxin B monotherapy for hospital-acquired pneumonia caused by CRE/CRAB in terms of 28-day mortality 2
• Recent evidence suggests that adding polymyxin B to high-dose tigecycline does not improve clinical outcomes in nosocomial pneumonia due to carbapenem-resistant K. pneumoniae and A. baumannii 3

Safety Considerations

Nephrotoxicity Risk

• Polymyxin B has significant nephrotoxicity potential, with acute kidney injury (AKI) occurring in approximately 50-53% of patients 2
• Polymyxin B should be used judiciously in patients with renal insufficiency 1
• Therapeutic drug monitoring (TDM) for polymyxin B can help reduce nephrotoxicity while maintaining efficacy 4

Hepatotoxicity Risk

• Tigecycline should be used cautiously in patients with liver insufficiency 1
• Tigecycline can cause elevated liver enzymes and abdominal pain 1

Fluoroquinolone Considerations

• Levofloxacin adds another potential toxicity profile including QT prolongation, tendinopathy, and CNS effects 1
• Using levofloxacin with tigecycline provides redundant gram-negative coverage without clear benefit 1

Alternative Approaches

• For CRE infections, newer agents like ceftazidime-avibactam, meropenem-vaborbactam, or cefiderocol are preferred if active in vitro 1
• For metallo-β-lactamase-producing CRE, ceftazidime-avibactam plus aztreonam combination is suggested 1
• For CRAB pulmonary infections, either tigecycline-based or polymyxin-based combination therapy can be considered based on patient factors 1
• For non-severe infections, under antibiotic stewardship considerations, monotherapy with an in vitro active old antibiotic is recommended 1

Practical Recommendations

• If combination therapy is necessary for MDR infections:

  • Determine MIC values for tigecycline against the isolate before initiating treatment 1
  • Consider high-dose tigecycline for pneumonia 1
  • Implement therapeutic drug monitoring for polymyxin B when available 4
  • Avoid this triple combination in patients with pre-existing renal or hepatic impairment 1

• For CRE infections specifically:

  • Newer β-lactam/β-lactamase inhibitors should be used preferentially when susceptible 1
  • For polymyxin-susceptible isolates, polymyxin B monotherapy has shown 73% clinical cure rates in some studies 5

Common Pitfalls to Avoid

• Using tigecycline for bloodstream infections where it has poor outcomes 1
• Underdosing tigecycline for respiratory infections 1
• Failing to monitor renal function when using polymyxin B 4, 6
• Using this triple combination when more targeted therapy with newer agents would be more effective and less toxic 1
• Continuing broad triple therapy when culture results allow for de-escalation 1