Vancomycin-resistant Staphylococcus aureus (VRSA) are strains of Staphylococcus aureus that have acquired resistance to the glycopeptide antibioticvancomycin.[3] Bacteria can acquire resistant genes either by random mutation or through the transfer of DNA from one bacterium to another. Resistance genes interfere with the normal antibiotic function and allow bacteria to grow in the presence of the antibiotic.[4] Resistance in VRSA is conferred by the plasmid-mediated vanA gene and operon.[5] Although VRSA infections are uncommon, VRSA is often resistant to other types of antibiotics and a potential threat to public health because treatment options are limited.[6] VRSA is resistant to many of the standard drugs used to treat S. aureus infections. Furthermore, resistance can be transferred from one bacterium to another.[5]
Mechanism of acquired resistance
Vancomycin-resistant Staphylococcus aureus was first reported in the United States in 2002.[5] To date, documented cases of VRSA have acquired resistance through uptake of a vancomycin resistance gene cluster from Enterococcus (i.e. VRE).[7] The acquired mechanism is typically the vanA gene and operon from a plasmid in Enterococcus faecium or Enterococcus faecalis.[5]
This mechanism differs from strains of vancomycin-intermediate Staphylococcus aureus (VISA), which appear to develop elevated MICs to vancomycin through sequential mutations resulting in a thicker cell wall and the synthesis of excess amounts of D-ala-D-ala residues.[8]
Three classes of vancomycin-resistant S. aureus have emerged that differ in vancomycin susceptibilities: vancomycin-intermediate S. aureus (VISA), heterogeneous vancomycin-intermediate S. aureus (hVISA), and high-level vancomycin-resistant S. aureus (VRSA).[10]
Vancomycin-intermediate S. aureus (VISA)
Vancomycin-intermediate S. aureus (VISA) (/ˈviːsə/ or /viːaɪɛseɪ/) was first identified in Japan in 1996[11] and has since been found in hospitals elsewhere in Asia, as well as in the United Kingdom, France, the U.S., and Brazil. It is also termed GISA (glycopeptide-intermediate Staphylococcus aureus), indicating resistance to all glycopeptide antibiotics. These bacterial strains present a thickening of the cell wall, which is believed to reduce the ability of vancomycin to diffuse into the division septum of the cell required for effective vancomycin treatment.[12]
Vancomycin-resistant S. aureus (VRSA)
High-level vancomycin resistance in S. aureus has been rarely reported.[13]In vitro and in vivo experiments reported in 1992 demonstrated that vancomycin resistance genes from Enterococcus faecalis could be transferred by gene transfer to S. aureus, conferring high-level vancomycin resistance to S. aureus.[14] Until 2002 such a genetic transfer was not reported for wild S. aureus strains. In 2002, a VRSA strain (/ˈvɜːrsə/ or /viːɑːrɛseɪ/) was isolated from a patient in Michigan.[15] The isolate contained the mecA gene for methicillin resistance. Vancomycin MICs of the VRSA isolate were consistent with the VanA phenotype of Enterococcus species, and the presence of the vanA gene was confirmed by polymerase chain reaction. The DNA sequence of the VRSA vanA gene was identical to that of a vancomycin-resistant strain of Enterococcus faecalis recovered from the same catheter tip. The vanA gene was later found to be encoded within a transposon located on a plasmid carried by the VRSA isolate. This transposon, Tn1546, confers vanA-type vancomycin resistance in enterococci.[16]
As of 2019, 52 VRSA strains have been identified in the United States, India, Iran, Pakistan, Brazil, and Portugal.[17]
Heterogeneous vancomycin-intermediate S. aureus (hVISA)
The definition of hVISA according to Hiramatsu et al. is a strain of Staphylococcus aureus that gives resistance to vancomycin at a frequency of 10−6 colonies or even higher.[18]
^CLSI (2023). M100 Performance Standards for Antimicrobial Susceptibility Standards (Report) (33 ed.). Wayne PA: Clinical and Laboratory Standards Institute. p. 8.
^Appelbaum PC (November 2007). "Reduced glycopeptide susceptibility in methicillin-resistant Staphylococcus aureus (MRSA)". Int. J. Antimicrob. Agents. 30 (5): 398–408. doi:10.1016/j.ijantimicag.2007.07.011. PMID17888634.