VanA vs VanB in Vancomycin-Resistant Enterococcus (VRE)
VanA confers high-level resistance to both vancomycin and teicoplanin, is typically plasmid-borne and transferable, while VanB confers variable vancomycin resistance but maintains teicoplanin susceptibility and is inducible only by vancomycin.
Key Mechanistic Differences
VanA Phenotype
- Resistance pattern: High-level resistance to both vancomycin (MIC ≥32 μg/mL) and teicoplanin 1
- Genetic characteristics: The vanA gene is frequently plasmid-borne and can be transferred in vitro to other gram-positive organisms including S. aureus, making it a significant public health concern 1
- Induction: Both vancomycin and teicoplanin induce resistance 2
- Prevalence: VanA is the predominant resistance determinant in clinical isolates, detected in 70 of 74 VRE isolates in one recent study 3 and in 8 of 17 VRE isolates in another 4
VanB Phenotype
- Resistance pattern: Variable levels of vancomycin resistance but remains susceptible to teicoplanin 5, 6
- Genetic characteristics: The VanS(B)-VanR(B) two-component regulatory system activates resistance genes differently than VanA 5
- Induction: Only vancomycin (not teicoplanin) acts as an inducer, which explains the teicoplanin susceptibility 5, 2
- Detection challenge: Automated laboratory methods may fail to consistently detect VanB phenotype, particularly moderate vancomycin resistance 1
Clinical Implications
Laboratory Detection
Automated systems frequently miss VanB resistance, particularly moderate resistance levels 1. The BD Phoenix system demonstrated major and very major errors for susceptibility testing in recent studies 7. A simple phenotypic method can distinguish between VanA and VanB: teicoplanin resistance induction by vancomycin occurs in VanB-VRE but not in VanA-VRE (which shows constitutive resistance to both agents) 2.
Treatment Considerations
- VanA isolates: Require alternatives to both vancomycin and teicoplanin
- VanB isolates: Teicoplanin may remain a therapeutic option, though clinical data are limited
- Recent data show that despite 82% ampicillin susceptibility in VRE E. faecalis, daptomycin remains the most frequently used agent (19%), highlighting a stewardship gap 8
Important Caveats
Vancomycin-Variable Enterococci
Be aware that vanA-positive isolates can appear phenotypically vancomycin-susceptible 7. Three phenotypically vancomycin-susceptible E. faecalis isolates were found to carry vanA, representing vancomycin-variable enterococci that could be missed without molecular testing 7.
Molecular Complexity
The VanB phenotype with vanA genotype can occur due to:
- Deletions in vanY and vanZ genes rather than vanS mutations 9
- Structural variations in Tn1546-like elements 10
- Differences in vanA gene expression levels 10
This discordance between genotype and phenotype underscores the need for both phenotypic and molecular testing approaches 7.
Transferability Risk
VanA poses greater epidemiologic risk because it is plasmid-borne and transferable to other gram-positive organisms, including the potential for transfer to S. aureus 1. This makes infection control and antimicrobial stewardship particularly critical for VanA-type VRE.