| Vancomycin-resistant Enterococcus | |
|---|---|
| Other names | Vancomycin-resistant enterococci |
 | |
| SEM micrograph of vancomycin-resistant enterococci | |
| Specialty | Microbiology |
| Prevention | Screen with peri-rectal swab [1] |
| Treatment | Linezolid [2] |
Vancomycin-resistant Enterococcus, or vancomycin-resistant enterococci (VRE), are bacterial strains of the genus Enterococcus that are resistant to the antibiotic vancomycin. [3]
Six different types of vancomycin resistance are shown by enterococcus: Van-A, Van-B, Van-C, Van-D, Van-E and Van-G. [4] The significance is that Van-A VRE is resistant to both vancomycin and teicoplanin, [5] Van-B VRE is resistant to vancomycin but susceptible to teicoplanin, [6] [7] and Van-C is only partly resistant to vancomycin.
The mechanism of resistance to vancomycin found in enterococcus involves the alteration of the peptidoglycan synthesis pathway. [8]
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. The D-alanyl-D-serine variation causes a six-fold loss of affinity between vancomycin and the peptide, likely due to steric hindrance. [9] [10]
To become vancomycin-resistant, vancomycin-sensitive enterococci typically obtain new DNA in the form of plasmids or transposons which encode genes that confer vancomycin resistance. [11] This acquired vancomycin resistance is distinguished from the natural vancomycin resistance of certain enterococcal species including E. gallinarum and E. casseliflavus/flavescens. [12] [13]
Once the individual has VRE, it is important to ascertain which strain. [14]
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. [1]
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 (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. [1] Detection of vancomycin resistance by the use of PCR targeting vanA and vanB can also be performed. [15] [16]
Ceftriaxone (a third generation cephalosporin) 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. [17] Lactobacillus rhamnosus GG (LGG), a strain of L. rhamnosus, was used successfully for the first time to treat gastrointestinal carriage of VRE. [18] In the US, linezolid is commonly used to treat VRE. [2] The combination of daptomycin and ampicillin is another option to treat VRE infections, especially for bacteremia. [19] For invasive vancomycin-resistant E. faecalis infections, both ampicillin-ceftriaxone and ampicillin-gentamicin combinations have been used successfully, with the latter specifically showing success in treating endocarditis. [20] If the VRE strain is vanB, teicoplanin and dalbavancin are suitable therapeutic options. [21] 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. [22]
High-level vancomycin-resistant E. faecalis and E. faecium are clinical isolates first documented in Europe in 1986 and the United States in 1987. [23] [24] 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 National Healthcare Safety Network from January 2006 to October 2007. [25] VRE can be carried by healthy people who have come into contact with the bacteria, usually in a hospital [26] (nosocomial infection), [27] although it is thought that a significant percentage of intensively farmed chickens also carry VRE. [28] 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. [29]
Ampicillin is an antibiotic belonging to the aminopenicillin class of the penicillin family. The drug is used to prevent and treat a number of bacterial infections, such as respiratory tract infections, urinary tract infections, meningitis, salmonellosis, and endocarditis. It may also be used to prevent group B streptococcal infection in newborns. It is used by mouth, by injection into a muscle, or intravenously.
Vancomycin is a glycopeptide antibiotic medication used to treat a number of bacterial infections. It is used intravenously as a treatment for complicated skin infections, bloodstream infections, endocarditis, bone and joint infections, and meningitis caused by methicillin-resistant Staphylococcus aureus. Blood levels may be measured to determine the correct dose. Vancomycin is also taken orally as a treatment for severe Clostridium difficile colitis. When taken orally it is poorly absorbed.
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 characteristics alone. Two species are common commensal organisms in the intestines of humans: E. faecalis (90–95%) and E. faecium (5–10%). Rare clusters of infections occur with other species, including E. casseliflavus, E. gallinarum, and E. raffinosus.
Methicillin-resistant Staphylococcus aureus (MRSA) is a group of gram-positive bacteria that are genetically distinct from other strains of Staphylococcus aureus. MRSA is responsible for several difficult-to-treat infections in humans. It caused more than 100,000 deaths worldwide attributable to antimicrobial resistance in 2019.
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, vancomycin-resistant enterococci (VRE), and methicillin-resistant Staphylococcus aureus (MRSA). The main uses are infections of the skin and pneumonia although it may be used for a variety of other infections including drug-resistant tuberculosis. It is used either by injection into a vein or by mouth.
Vancomycin-resistant Staphylococcus aureus (VRSA) are strains of Staphylococcus aureus that have acquired resistance to the glycopeptide antibiotic vancomycin. 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 a 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.
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. faecalis is found in healthy humans and can be used as a probiotic. The probiotic strains such as Symbioflor1 and EF-2001 are characterized by the lack of specific genes related to drug resistance and pathogenesis. As an opportunistic pathogen, E. faecalis can cause life-threatening infections, especially in the nosocomial (hospital) environment, where the naturally high levels of antibiotic resistance found in E. faecalis contribute to its pathogenicity. E. faecalis has been frequently found in reinfected, root canal-treated teeth in prevalence values ranging from 30% to 90% of the cases. Re-infected root canal-treated teeth are about nine times more likely to harbor E. faecalis than cases of primary infections.
Oritavancin, sold under the brand name Orbactiv among others, is a semisynthetic glycopeptide antibiotic medication for the treatment of serious Gram-positive bacterial infections. Its chemical structure as a lipoglycopeptide is similar to vancomycin.
Enterococcus faecium is a Gram-positive, gamma-hemolytic or non-hemolytic bacterium in the genus Enterococcus. It can be commensal in the gastrointestinal tract of humans and animals, but it may also be pathogenic, causing diseases such as neonatal meningitis or endocarditis.
Ceftobiprole, sold under the brand name Zevtera among others, is a fifth-generation cephalosporin antibacterial used for the treatment of hospital-acquired pneumonia and community-acquired pneumonia. It is marketed by Basilea Pharmaceutica under the brand names Zevtera and Mabelio. Like other cephalosporins, ceftobiprole exerts its antibacterial activity by binding to important penicillin-binding proteins and inhibiting their transpeptidase activity which is essential for the synthesis of bacterial cell walls. Ceftobiprole has high affinity for penicillin-binding protein 2a of methicillin-resistant Staphylococcus aureus strains and retains its activity against strains that express divergent mecA gene homologues. Ceftobiprole also binds to penicillin-binding protein 2b in Streptococcus pneumoniae (penicillin-intermediate), to penicillin-binding protein 2x in Streptococcus pneumoniae (penicillin-resistant), and to penicillin-binding protein 5 in Enterococcus faecalis.
Dalbavancin, sold under the brand names Dalvance in the US and Xydalba in the EU among others, is a second-generation lipoglycopeptide antibiotic medication. It belongs to the same class as vancomycin, the most widely used and one of the treatments available to people infected with methicillin-resistant Staphylococcus aureus (MRSA).
Enterococcus gallinarum is a species of Enterococcus. E. gallinarum demonstrates an inherent, low-level resistance to vancomycin. Resistance is due to a chromosomal gene, vanC, which encodes for a terminal D-alanine-D-serine instead of the usual D-alanine-D-alanine in cell wall peptidoglycan precursor proteins. That is a separate mechanism than the vancomycin resistance seen in VRE isolates of E. faecium and E. faecalis which is mediated by vanA or vanB. This species is known to cause clusters of infection, although it considered very rare. It is the only other known enterococcal species besides E. faecium and E. faecalis known to cause outbreaks and spread in hospitals.
Sophoraflavanone G is a volatile phytoncide, released into the atmosphere, soil and ground water, by members of the Sophora genus. Sophora pachycarpa, and Sophora exigua; all found to grow within the United States in a variety of soil types, within temperate conditions, no lower than 0 °F. Sophoraflavanone G is released in order to protect the plant against harmful protozoa, bacteria, and fungi. Sophoraflavanone G, also called kushenin, is a flavonoid compound.
In molecular biology, VanY are protein domains found in enzymes named metallopeptidases. They are vital to bacterial cell wall synthesis and antibiotic resistance.
Enterococcus malodoratus is a species of the genus Enterococcus and a gram positive bacteria capable of opportunistic pathogenic response. These microbes have a thick polypeptide layer. Enterococcus can be found in the gastrointestinal tracts of humans and other mammals. In a study on the enterococcal flora of swine, E. malodoratus was found in the intestines and feces. It was not identified within the tonsils of swine, nor within cats, calves, dogs, horse, or poultry. The name "malodoratus" translates to "ill smelling".
ESKAPE is an acronym comprising the scientific names of six highly virulent and antibiotic resistant bacterial pathogens including: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. The acronym is sometimes extended to ESKAPEE to include Escherichia coli. This group of Gram-positive and Gram-negative bacteria can evade or 'escape' commonly used antibiotics due to their increasing multi-drug resistance (MDR). As a result, throughout the world, they are the major cause of life-threatening nosocomial or hospital-acquired infections in immunocompromised and critically ill patients who are most at risk. P. aeruginosa and S. aureus are some of the most ubiquitous pathogens in biofilms found in healthcare. P. aeruginosa is a Gram-negative, rod-shaped bacterium, commonly found in the gut flora, soil, and water that can be spread directly or indirectly to patients in healthcare settings. The pathogen can also be spread in other locations through contamination, including surfaces, equipment, and hands. The opportunistic pathogen can cause hospitalized patients to have infections in the lungs, blood, urinary tract, and in other body regions after surgery. S. aureus is a Gram-positive, cocci-shaped bacterium, residing in the environment and on the skin and nose of many healthy individuals. The bacterium can cause skin and bone infections, pneumonia, and other types of potentially serious infections if it enters the body. S. aureus has also gained resistance to many antibiotic treatments, making healing difficult. Because of natural and unnatural selective pressures and factors, antibiotic resistance in bacteria usually emerges through genetic mutation or acquires antibiotic-resistant genes (ARGs) through horizontal gene transfer - a genetic exchange process by which antibiotic resistance can spread.
Kerry L. LaPlante is an American pharmacist, academic and researcher. She is the Dean at the University of Rhode Island College of Pharmacy. She is a Professor of Pharmacy and former department Chair of the Department of Pharmacy Practice at the University of Rhode Island, an Adjunct Professor of Medicine at Brown University, an Infectious Diseases Pharmacotherapy Specialist, and the Director of the Rhode Island Infectious Diseases Fellowship and Research Programs at the Veterans Affairs Medical Center in Providence, Rhode Island.
Antimicrobial nanotechnology is the study of using biofilms to disrupt a microbe's cell membrane, deliver an electric charge to the microbe, and cause immediate cellular death via a "mechanical kill" process, preventing the original microbe from mutating into a superbug.
This article incorporates text from this source, which is in the public domain .The LightCycler instrument (Roche Diagnostics Corporation) is used to detect vanA and vanB using a rapid real-time PCR assay(Figure 3). This method is more sensitive and faster (~3.5 vs >72 hours) than culture for detecting VRE colonization.47 The assay detects the presence of genes associated with vancomycin resistance in enterococci, vanA and vanB.
The first reports of vancomycin-resistant enterococci (later classified as VanA type of resistance) involved strains of E. faecium that were resistant to vancomycin and teicoplanin (another glycopeptide) and that were isolated from patients in France and England in 1986. Vancomycin-resistant E. faecalis, subsequently classified as VanB type, was recovered from patients in Missouri in 1987.
