Teicoplanin Resistance in Enterococcus faecalis: Associated Genes
Teicoplanin resistance in Enterococcus faecalis is primarily associated with the vanA gene, while vanB-type E. faecalis can develop teicoplanin resistance through mutations in the vanB gene cluster. 1, 2
Glycopeptide Resistance Phenotypes in Enterococci
- Enterococci display several phenotypes of vancomycin resistance (vanA through vanE), with vanA, vanB, and vanC being most commonly associated with infective endocarditis 1
- The vanA phenotype is characterized by high-level vancomycin resistance (MIC ≥64 μg/mL) and teicoplanin resistance 1
- The vanB phenotype typically shows intermediate to high-level vancomycin resistance (MIC 16-512 μg/mL) but initial susceptibility to teicoplanin 1, 2
- The vanC phenotype exhibits low to intermediate-level resistance (MIC 2-32 μg/mL) 1
Genetic Basis of Teicoplanin Resistance
- The vanA gene is primarily responsible for teicoplanin resistance in E. faecalis and is found in both E. faecium and some strains of E. faecalis 1, 2
- VanB-type E. faecalis can develop teicoplanin resistance through mutations in the vanB gene cluster, as demonstrated in clinical isolates 2
- In VanB-type strains that develop teicoplanin resistance, SDS-PAGE analysis has shown constitutive production of a normally inducible 41-kDa protein 2
Development of Teicoplanin Resistance
- VanB-type E. faecalis can acquire teicoplanin resistance in vivo during treatment, challenging the utility of teicoplanin for infections caused by vancomycin-resistant enterococci 2
- In vitro studies show that teicoplanin can select for teicoplanin-resistant mutants at frequencies of 10^-6 to 10^-7 3
- Two-step acquisition of resistance to teicoplanin-gentamicin combinations has been observed in experimental models, requiring mutations affecting both antibiotics 3
Clinical Implications
- Susceptibility testing should include penicillin, vancomycin (MIC determination), and testing for high-level resistance to aminoglycosides 1
- For strains resistant to β-lactams, vancomycin, or aminoglycosides, in vitro susceptibility to daptomycin and linezolid should be obtained 1
- Vancomycin-resistant E. faecalis strains are less common (approximately 3%) compared to vancomycin-resistant E. faecium 4
- For multidrug-resistant enterococcal infections, consultation with infectious disease specialists is recommended 1
Treatment Considerations
- Combination therapy is often required for enterococcal infections with glycopeptide resistance 1, 5
- Synergistic bactericidal activity has been demonstrated with double β-lactam combinations (imipenem and ampicillin or cephalosporins plus ampicillin) for some resistant E. faecalis strains 1
- Despite low-level VanB-type resistance, combination therapy with a glycopeptide and aminoglycoside (if no high-level aminoglycoside resistance) can provide effective bactericidal activity 5