Vancomycin-resistant ''Enterococcus'', or vancomycin-resistant enterococci (VRE), are

bacterial Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among the ...

strains of the genus ''

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 ch ...

'' that are resistant to the

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...

vancomycin Vancomycin is a glycopeptide antibiotic medication used to treat certain bacterial infections. It is administered intravenously ( injection into a vein) to treat complicated skin infections, bloodstream infections, endocarditis, bone an ...

Mechanism of acquired resistance

Six different types of vancomycin resistance are shown by enterococcus: Van-A, Van-B, Van-C, Van-D, Van-E and Van-G. The significance is that Van-A VRE is resistant to both vancomycin and teicoplanin, Van-B VRE is resistant to vancomycin but susceptible to teicoplanin, and Van-C is only partly resistant to vancomycin. The mechanism of resistance to vancomycin found in enterococcus involves the alteration of the

peptidoglycan Peptidoglycan or murein is a unique large macromolecule, a polysaccharide, consisting of sugars and amino acids that forms a mesh-like layer (sacculus) that surrounds the bacterial cytoplasmic membrane. The sugar component consists of alternating ...

synthesis pathway. The D-alanyl-D-lactate variation results in the loss of one hydrogen-bonding interaction (four, as opposed to five for D-alanyl-D-alanine) being possible between vancomycin and the

peptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty am ...

. The D-alanyl-D-serine variation causes a six-fold loss of affinity between vancomycin and the peptide, likely due to

steric hindrance Steric effects arise from the spatial arrangement of atoms. When atoms come close together there is generally a rise in the energy of the molecule. Steric effects are nonbonding interactions that influence the shape ( conformation) and reactivi ...

. To become vancomycin-resistant, vancomycin-sensitive enterococci typically obtain new DNA in the form of

plasmids 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 and ...

transposon A transposable element (TE), also transposon, or jumping gene, is a type of mobile genetic element, a nucleic acid sequence in DNA that can change its position within a genome. The discovery of mobile genetic elements earned Barbara McClinto ...

s which encode

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

s that confer vancomycin resistance. This acquired vancomycin resistance is distinguished from the natural vancomycin resistance of certain enterococcal species including ''E. gallinarum'' and ''E. ''.

Screening and diagnosis

Screening for VRE can be accomplished in a number of ways. For inoculating peri-rectal/anal swabs or stool specimens directly, one method uses bile esculin azide agar plates containing 6 μg/ml of vancomycin. Black colonies should be identified as an enterococcus to species level and further confirmed as vancomycin resistant by an MIC method before reporting as VRE. Vancomycin resistance can be determined for enterococcal colonies available in pure culture by inoculating a suspension of the organism onto a commercially available brain heart infusion agar (BHIA) plate containing 6 μg/ml vancomycin. The

Clinical and Laboratory Standards Institute The Clinical and Laboratory Standards Institute (CLSI) is a volunteer-driven, membership-supported, not-for-profit, standards development organization. CLSI promotes the development and use of voluntary laboratory consensus standards and guidelin ...

(CLSI) recommends performing a vancomycin MIC test and also motility and pigment production tests to distinguish species with acquired resistance (vanA and vanB) from those with vanC intrinsic resistance. Detection of vancomycin resistance by the use of PCR targeting ''vanA'' and ''vanB'' can also be performed. Once the individual has VRE, it is important to ascertain which strain.

Treatment of infection

Ceftriaxone Ceftriaxone, sold under the brand name Rocephin, is a third-generation cephalosporin antibiotic used for the treatment of a number of bacterial infections. These include middle ear infections, endocarditis, meningitis, pneumonia, bone and joi ...

(a third generation

cephalosporin The cephalosporins (sg. ) are a class of β-lactam antibiotics originally derived from the fungus '' Acremonium'', which was previously known as ''Cephalosporium''. Together with cephamycins, they constitute a subgroup of β-lactam antibio ...

) use is a risk factor for colonization and infection by VRE, and restriction of cephalosporin usage has been associated with decreased VRE infection and transmission in hospitals. ''Lactobacillus rhamnosus'' GG (LGG), a strain of ''L. rhamnosus'', was used successfully for the first time to treat gastrointestinal carriage of VRE. In the US, linezolid is commonly used to treat VRE. The combination of daptomycin and

ampicillin Ampicillin is an antibiotic belonging to the aminopenicillin class of the penicillin family. The drug is used to prevent and treat several bacterial infections, such as respiratory tract infections, urinary tract infections, meningitis, s ...

is another option to treat VRE infections, especially for bacteremia. For invasive vancomycin-resistant ''E. faecalis'' infections, both ampicillin-ceftriaxone and ampicillin-

gentamicin Gentamicin is an aminoglycoside 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 amo ...

combinations have been used successfully, with the latter specifically showing success in treating endocarditis. If the VRE strain is vanB, teicoplanin and dalbavancin are suitable therapeutic options. Another antibiotic often used as off-label salvage therapy in systemic VRE infections is oritavancin, a semisynthetic glycopeptide that has demonstrated synergic activity with

fosfomycin Fosfomycin, sold under the brand name Monurol among others, is an antibiotic primarily used to treat lower urinary tract infections. It is not indicated for kidney infections. Occasionally it is used for prostate infections. It is generally ...

History

High-level vancomycin-resistant ''E. faecalis'' and ''E. faecium'' are clinical isolates first documented in Europe in 1986 and the United States in 1987. In the United States, vancomycin-resistant ''E. faecium'' was associated with 4% of healthcare-associated infections reported to the

Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the National public health institutes, national public health agency of the United States. It is a Federal agencies of the United States, United States federal agency under the United S ...

National Healthcare Safety Network from January 2006 to October 2007. VRE can be carried by healthy people who have come into contact with the bacteria, usually in a hospital (

nosocomial infection A hospital-acquired infection, also known as a nosocomial infection (from the Greek , meaning "hospital"), is an infection that is acquired in a hospital or other healthcare facility. To emphasize both hospital and nonhospital settings, it is s ...

), although it is thought that a significant percentage of intensively farmed chickens also carry VRE. Other regions have noted a similar distribution, but with increased incidence of VRE. For example, a 2006 study of nosocomial VRE revealed a rapid spread of resistance among enterococci along with an emerging shift in VRE distribution in the Middle East region, such as Iran. Treatment failures in enterococcal infections result from inadequate information regarding glycopeptide resistance of endemic enterococci due to factors such as the presence of VanA and VanB. The study from Iran reported the first case of VRE isolates that carried VanB gene in enterococcal strains from Iran. This study also noted the first documented isolation of nosocomial ''E. raffinosus'' and ''E. mundtii'' in the Middle East region.

References

External links

PubMed
{{DEFAULTSORT:Vancomycin-Resistant Enterococcus Lactobacillales Antibiotic-resistant bacteria Healthcare-associated infections