Genomic insights of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) with reduced teicoplanin susceptibility: A case of fatal necrotizing fasciitis.

Objectives: Glycopeptides are increasingly being used to treat multiresistant methicillin-resistant Staphylococcus aureus (MRSA) infections. Here we report an MRSA isolate with low-level teicoplanin resistance (isolate VB26276) recovered from a patient treated with teicoplanin for fatal necrotizing fasciitis.

Methods: Minimum inhibitory concentrations (MICs) of MRSA isolates to vancomycin and teicoplanin were determined by Etest. Reduced glycopeptide susceptibility was screened by Etest GRD (glycopeptide resistance detection) and population analysis profile (PAP) method. Next-generation sequencing (NGS) was also performed to determine the molecular mechanism of antimicrobial resistance and virulence.

Results: The teicoplanin MIC of MRSA isolate VB26276 was 4μg/mL. NGS showed the presence of mutations in the tcaA and tcaB genes of the tcaRAB operon that determines the level of teicoplanin resistance. In addition, a mutation in the vraR gene was found to be associated with teicoplanin resistance, but not with vancomycin heteroresistance.

Conclusion: Teicoplanin resistance may occur due to point mutations in the teicoplanin resistance operon tcaRAB. Further studies are warranted to determine the contribution of point mutations in tcaRAB to reduced teicoplanin susceptibility.