Vancomycin-resistant Staphylococcus aureus

Mechanism of acquired resistance

Vancomycin-resistant Staphylococcus aureus was first reported in the United States in 2002. To date, documented cases of VRSA have acquired resistance through uptake of a vancomycin resistance gene cluster from Enterococcus (i.e. VRE). The acquired mechanism is typically the vanA gene and operon from a plasmid in Enterococcus faecium or Enterococcus faecalis.

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.

Diagnosis

The diagnosis of vancomycin-resistant Staphylococcus aureus (VRSA) is performed by performing susceptibility testing on a single S. aureus isolate to vancomycin. This is accomplished by first assessing the isolate's minimum inhibitory concentration (MIC) using standard laboratory methods, including disc diffusion, gradient strip diffusion, and automated antimicrobial susceptibility testing systems. Once the MIC is known, resistance is determined by comparing the MIC with established breakpoints.{{cite report

Resistant or "R" designations are assigned based on agreed upon values called breakpoints. Breakpoints are published by standards development organizations such as the U.S. Clinical and Laboratory Standards Institute, the British Society for Antimicrobial Chemotherapy and the European Committee on Antimicrobial Susceptibility Testing.

Treatment of infection

When the minimum inhibitory concentration of vancomycin is 2 µg/mL, alternative antibiotics should be used. The approach is to treat with at least one agent to which the bacteria known to be susceptible by in vitro testing. The agents that are used include daptomycin, linezolid, telavancin, ceftaroline, and quinupristin–dalfopristin. For people with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia in the setting of vancomycin failure the Infectious Diseases Society of America recommends high-dose daptomycin, if the isolate is susceptible, in combination with another agent (e.g., gentamicin, rifampin, linezolid, trimethoprim/sulfamethoxazole, or a beta-lactam antibiotic).

History

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).

Vancomycin-intermediate ''S. aureus'' (VISA)

Vancomycin-intermediate S. aureus (VISA) ( or ) was first identified in Japan in 1996 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.

Vancomycin-resistant ''S. aureus'' (VRSA)

High-level vancomycin resistance in S. aureus has rarely been reported. 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. Until 2002 such a genetic transfer was not reported for wild S. aureus strains. In 2002, a VRSA strain ( or ) was isolated from a patient in Michigan. 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.

As of 2019, 52 VRSA strains have been identified in the United States, India, Iran, Pakistan, Brazil, and Portugal.

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.

References

References

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