Does colistin (polymyxin E) have intrinsic resistance to Stenotrophomonas?

Colistin and Stenotrophomonas maltophilia: Intrinsic Resistance

Stenotrophomonas maltophilia is intrinsically resistant to colistin (polymyxin E), making colistin ineffective as monotherapy against this organism.

Mechanism of Intrinsic Resistance

Stenotrophomonas maltophilia possesses natural resistance to colistin due to several mechanisms:

• Intrinsic cell membrane characteristics that prevent colistin binding
• Natural efflux systems that pump colistin out of bacterial cells
• Inherent lipopolysaccharide (LPS) modifications that reduce colistin's ability to disrupt the bacterial membrane

Evidence Supporting Intrinsic Resistance

The evidence clearly demonstrates that S. maltophilia has intrinsic resistance to colistin:

1. Multiple studies show high minimum inhibitory concentrations (MICs) for colistin against S. maltophilia isolates 1, 2, 3

2. Guidelines recognize S. maltophilia as intrinsically resistant to colistin, listing it among organisms with natural resistance to polymyxins 4

3. Clinical evidence shows poor outcomes when colistin is used as monotherapy against S. maltophilia infections 5, 6

Treatment Approaches for S. maltophilia

Given the intrinsic resistance to colistin, the recommended treatment options for S. maltophilia infections are:

First-line therapy:

• Trimethoprim-sulfamethoxazole (TMP-SMX) remains the drug of choice for susceptible isolates

Alternative options for resistant isolates:

• Minocycline (highest susceptibility rate at 92.7% among resistant isolates) 6
• Fluoroquinolones (levofloxacin, moxifloxacin) for susceptible isolates
• Tigecycline as a second-line option

Combination therapy options:

• Colistin may have synergistic activity when combined with other agents despite intrinsic resistance:
  • Colistin + rifampin shows significant synergy (92% of isolates) 1, 2
  • Colistin + tigecycline demonstrates synergy in 88% of isolates 1
  • Colistin + N-acetylcysteine shows synergistic activity, particularly against biofilms 3
  • Doxycycline + aerosolized colistin has shown clinical success in case reports 5

Clinical Implications

1. Never use colistin as monotherapy for S. maltophilia infections due to intrinsic resistance

2. Consider combination therapy with colistin only when:

   • Other options have failed
   • Synergistic partner drugs are available
   • The infection involves biofilms or is multidrug-resistant

3. For respiratory infections with S. maltophilia, aerosolized colistin combined with systemic antibiotics may be considered as a salvage option 5

Pitfalls to Avoid

• Relying on colistin monotherapy against S. maltophilia will lead to treatment failure
• Failing to perform susceptibility testing for alternative agents
• Not considering combination therapy for difficult-to-treat infections
• Overlooking the potential for synergistic combinations despite intrinsic resistance to individual agents

In summary, while S. maltophilia has intrinsic resistance to colistin, strategic combination therapy approaches may still have a role in managing difficult-to-treat infections caused by this organism.