Which organisms are not covered by polymyxin (colistin or polymyxin B)?

Polymyxin Coverage Gaps

Polymyxins (colistin and polymyxin B) have NO activity against Gram-positive bacteria, fungi, Gram-negative cocci, and among Gram-negative bacilli they do not cover Proteus species, Serratia marcescens, Burkholderia cepacia, and Stenotrophomonas maltophilia. 1

Organisms NOT Covered by Polymyxins

Gram-Positive Bacteria

• All Gram-positive bacteria are intrinsically resistant to polymyxin B, including Staphylococcus species, Streptococcus species, and Enterococcus species. 1
• The mechanism of resistance is related to the polymyxin's inability to penetrate the thick peptidoglycan layer of Gram-positive cell walls. 1

Fungi

• All fungal organisms are resistant to polymyxins, as these agents target bacterial lipopolysaccharide structures not present in fungal cell membranes. 1

Gram-Negative Cocci

• All Gram-negative cocci are resistant to polymyxins, including Neisseria species and Moraxella catarrhalis. 1

Gram-Negative Bacilli with Intrinsic Resistance

Proteus Species

• The entire Proteus group (Proteus mirabilis, Proteus vulgaris, and related species) demonstrates intrinsic resistance to polymyxins. 1
• This is a critical gap because Proteus species are common causes of urinary tract infections and wound infections. 1

Stenotrophomonas maltophilia

• Stenotrophomonas maltophilia shows significant polymyxin resistance, with 30% of tested isolates demonstrating resistance in surveillance studies. 2
• This organism is an important nosocomial pathogen, particularly in immunocompromised patients and those with cystic fibrosis. 2

Other Intrinsically Resistant Gram-Negative Bacilli

• Serratia marcescens exhibits intrinsic resistance to polymyxins through lipopolysaccharide modifications. 3
• Burkholderia cepacia is naturally resistant to polymyxins and represents a therapeutic challenge in cystic fibrosis patients. 3

Acquired Resistance in Otherwise Susceptible Organisms

Enterobacteriaceae

• While most Enterobacteriaceae are susceptible, acquired resistance is emerging, particularly in Klebsiella species and Enterobacter species. 3, 4
• Resistance rates in Klebsiella spp. are increasing in the Asia-Pacific and Latin American regions, with a statistically significant upward trend. 4
• The mobilized colistin resistance (mcr) gene enables horizontal transmission of resistance among Enterobacteriaceae. 5

Pseudomonas aeruginosa

• Although generally susceptible, a significant proportion of Pseudomonas aeruginosa isolates demonstrate polymyxin resistance, particularly in certain geographic regions. 2
• Resistance rates vary by location but can reach 30% in some surveillance studies. 2

Acinetobacter baumannii

• While most Acinetobacter baumannii strains remain susceptible to polymyxins, resistance is increasing globally, particularly with repeated polymyxin exposure. 3, 4
• Heteroresistance (subpopulations with reduced susceptibility) is a growing concern that may lead to treatment failure. 6

Clinical Implications and Pitfalls

Critical Testing Requirements

• Susceptibility testing must be performed whenever polymyxin use is considered, as resistance cannot be predicted based on organism identification alone. 2
• Automated susceptibility methods are unreliable for polymyxins; broth microdilution or agar dilution should be used. 2

Geographic Variation

• Polymyxin resistance prevalence varies significantly by geographic location, with higher rates in Asia-Pacific and Latin American regions. 4
• Local antibiograms should guide empiric therapy decisions. 4

Mechanism of Resistance

• The most common mechanism of acquired polymyxin resistance involves modification of bacterial outer membrane lipopolysaccharide, reducing the drug's ability to bind and disrupt the cell membrane. 3
• This mechanism can develop during therapy, particularly with suboptimal dosing or monotherapy. 3