Vancomycin-resistant ''Staphylococcus aureus'' (VRSA) are strains of ''

Staphylococcus aureus ''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often positive ...

'' that have become resistant to the

glycopeptide antibiotic Glycopeptide antibiotics are a class of drugs of microbial origin that are composed of glycosylated cyclic or polycyclic nonribosomal peptides. Significant glycopeptide antibiotics include the anti-infective antibiotics vancomycin, teicoplanin, ...

vancomycin Vancomycin is a glycopeptide antibiotic medication used to treat a number of bacterial infections. It is recommended intravenously as a treatment for complicated skin infections, bloodstream infections, endocarditis, bone and joint infections, ...

Mechanism of acquired resistance

Strains of hVISA and vancomycin-intermediate ''Staphylococcus aureus'' (VISA) do not have resistant genes found in ''

Enterococcus ''Enterococcus'' is a large genus of lactic acid bacteria of the phylum Bacillota. Enterococci are gram-positive cocci that often occur in pairs (diplococci) or short chains, and are difficult to distinguish from streptococci on physical char ...

'' and the proposed mechanisms of resistance include the sequential mutations resulting in a thicker cell wall and the synthesis of excess amounts of D-ala-D-ala residues. VRSA strain acquired the

resistance gene cluster ''vanA'' from VRE.

Diagnosis

The diagnosis of vancomycin-resistant Staphylococcus aureus can be done with disk diffusion(and VA screen plate)

Treatment of infection

For isolates with a

minimum inhibitory concentration In microbiology, the minimum inhibitory concentration (MIC) is the lowest concentration of a chemical, usually a drug, which prevents visible growth of a bacterium or bacteria. MIC depends on the microorganism, the affected human being (in vivo onl ...

(MIC) , an alternative to

should be used. The approach is to treat with at least one agent to which VISA/VRSA is known to be susceptible by ''

in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...

'' testing. The agents that are used include

daptomycin Daptomycin, sold under the brand name Cubicin among others, is a lipopeptide antibiotic used in the treatment of systemic and life-threatening infections caused by Gram-positive organisms. Daptomycin was removed from the World Health Organiza ...

linezolid Linezolid is an antibiotic used for the treatment of infections caused by Gram-positive bacteria that are resistant to other antibiotics. Linezolid is active against most Gram-positive bacteria that cause disease, including streptococci, van ...

telavancin Telavancin (trade name Vibativ) is a bactericidal lipoglycopeptide for use in MRSA or other Gram-positive infections. Telavancin is a semi-synthetic derivative of vancomycin. The FDA approved the drug in September 2009 for complicated skin and ...

ceftaroline Ceftaroline fosamil (INN) , brand name Teflaro in the US and Zinforo in Europe, is a cephalosporin antibiotic with anti-MRSA activity. Ceftaroline fosamil is a prodrug of ceftaroline. It is active against methicillin-resistant ''Staphylococc ...

, quinupristin–dalfopristin. For people with methicillin-resistant ''Staphylococcus aureus'' (MRSA)

bacteremia Bloodstream infections (BSIs), which include bacteremias when the infections are bacterial and fungemias when the infections are fungal, are infections present in the blood. Blood is normally a sterile environment, so the detection of microb ...

in the setting of vancomycin failure the IDSA recommends high-dose

, if the isolate is susceptible, in combination with another agent (e.g.

gentamicin Gentamicin is an antibiotic used to treat several types of bacterial infections. This may include bone infections, endocarditis, pelvic inflammatory disease, meningitis, pneumonia, urinary tract infections, and sepsis among others. It is not e ...

rifampin Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), ''Mycobacterium avium'' complex, leprosy, and Legionnaires’ disease. It is almost always used tog ...

, TMP-SMX, or a

beta-lactam A beta-lactam (β-lactam) ring is a four-membered lactam. A ''lactam'' is a cyclic amide, and ''beta''-lactams are named so because the nitrogen atom is attached to the β-carbon atom relative to the carbonyl. The simplest β-lactam possible i ...

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 Japan ( ja, 日本, or , and formally , ''Nihonkoku'') is an island country in East Asia. It is situated in the northwest Pacific Ocean, and is bordered on the west by the Sea of Japan, while extending from the Sea of Okhotsk in the north ...

in 1996 and has since been found in hospitals elsewhere in

Asia Asia (, ) is one of the world's most notable geographical regions, which is either considered a continent in its own right or a subcontinent of Eurasia, which shares the continental landmass of Afro-Eurasia with Africa. Asia covers an area ...

, as well as in

the United Kingdom The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain, is a country in Europe, off the north-western coast of the continental mainland. It comprises England, Scotland, Wales and North ...

France France (), officially the French Republic ( ), is a country primarily located in Western Europe. It also comprises of Overseas France, overseas regions and territories in the Americas and the Atlantic Ocean, Atlantic, Pacific Ocean, Pac ...

, the

U.S. The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territori ...

, and

Brazil Brazil ( pt, Brasil; ), officially the Federative Republic of Brazil (Portuguese: ), is the largest country in both South America and Latin America. At and with over 217 million people, Brazil is the world's fifth-largest country by area ...

. 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. S aureus blood agar

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

High-level vancomycin resistance in ''S. aureus'' has been rarely reported. ''

In vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...

'' and ''

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...

'' experiments reported in 1992 demonstrated that vancomycin resistance genes from ''

Enterococcus faecalis ''Enterococcus faecalis'' – formerly classified as part of the group D ''Streptococcus'' system – is a Gram-positive, commensal bacterium inhabiting the gastrointestinal tracts of humans. Like other species in the genus ''Enterococcus'', ''E ...

'' could be transferred by

gene transfer Horizontal gene transfer (HGT) or lateral gene transfer (LGT) is the movement of genetic material between unicellular and/or multicellular organisms other than by the ("vertical") transmission of DNA from parent to offspring (reproduction). HG ...

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 ''

'' species, and the presence of the ''vanA'' gene was confirmed by

polymerase chain reaction The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies (complete or partial) of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) t ...

. 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 A transposable element (TE, transposon, or jumping gene) is a nucleic acid sequence in DNA that can change its position within a genome, sometimes creating or reversing mutations and altering the cell's genetic identity and genome size. Transpo ...

located on a

plasmid A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria; how ...

carried by the VRSA isolate. This transposon, Tn''1546'', confers ''vanA''-type vancomycin resistance in enterococci.

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

External links

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