Vancomycin Intermediate-resistant Staphylococcus Aureus

Vancomycin-resistant ''Staphylococcus aureus'' (VRSA) are strains of ''Staphylococcus aureus'' that have acquired resistance to the glycopeptide antibiotic vancomycin. Bacteria can acquire resistance 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. Resistance in VRSA is conferred by the plasmid-mediated ''vanA'' gene and operon. 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. 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.

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.

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 , 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, Tn''1546'', 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.

See also

* Drug resistance

References

Further reading

*

External links

PubMed

{{DEFAULTSORT:Vancomycin-Resistant Staphylococcus Aureus
Staphylococcaceae
Bacterial diseases
Antibiotic-resistant bacteria
Staphylococcus