Vancomycin-resistant Staphylococcus aureus
Encyclopedia
Vancomycin-resistant Staphylococcus aureus refers to strains of Staphylococcus aureus
that have become resistant
to the glycopeptide antibiotic
vancomycin
. With the increase of staphylococcal resistance to methicillin
, vancomycin (or another glycopeptide antibiotic, teicoplanin
) is often a treatment of choice in infections with methicillin-resistant S. aureus
(MRSA). Three classes of vancomycin-resistant S. aureus have emerged that differ in vancomycin susceptibilities
: vancomycin-intermediate S. aureus (VISA), heterogenous vancomycin-intermediate S. aureus (hVISA), and high-level vancomycin-resistant S. aureus (VRSA).
High-level vancomycin resistance in S. aureus has been rarely reported. However, these strains may also be resistant to meropenem
and imipenem
, two other antibiotics that can be used in sensitive Staphylococcus strains.
in 1996 and has since been found in hospitals in the United Kingdom, France
, the U.S.
, Asia
, 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.
Even with the absence of high-level resistance to vancomycin, another concern posed by the presence of VISA is the increased difficulty in prescribing treatments, especially in situations where an effective treatment for an infection is needed urgently, before detailed resistance profiles can be obtained. In hospitals already endemic with multiresistant
MRSA, the appearance of VRSA would make the treatment of infected patients much more difficult.
was found by Rockefeller University
to be effective as of 2008. Linezolid
, quinupristin/dalfopristin
, daptomycin
and tigecycline
are treatments of consideration.
and in vivo
experiments reported in 1992 demonstrated that vancomycin resistance genes from Enterococcus faecalis
could be transferred by horizontal 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 was isolated from the catheter tip of a diabetic, renal dialysis 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.
Since 2002, ten additional VRSA isolates have been reported, eight from the United States, one from Iran, and one from India.
, quinupristin/dalfopristin
and daptomycin
are treatments of consideration.
Staphylococcus aureus
Staphylococcus aureus is a facultative anaerobic Gram-positive coccal bacterium. It is frequently found as part of the normal skin flora on the skin and nasal passages. It is estimated that 20% of the human population are long-term carriers of S. aureus. S. aureus is the most common species of...
that have become resistant
Antibiotic resistance
Antibiotic resistance is a type of drug resistance where a microorganism is able to survive exposure to an antibiotic. While a spontaneous or induced genetic mutation in bacteria may confer resistance to antimicrobial drugs, genes that confer resistance can be transferred between bacteria in a...
to the glycopeptide antibiotic
Glycopeptide antibiotic
Glycopeptide antibiotics are a class of antibiotic drugs. The class is composed of glycosylated cyclic or polycyclic nonribosomal peptides. Significant glycopeptide antibiotics include vancomycin, teicoplanin, telavancin, bleomycin, ramoplanin, and decaplanin....
vancomycin
Vancomycin
Vancomycin INN is a glycopeptide antibiotic used in the prophylaxis and treatment of infections caused by Gram-positive bacteria. It has traditionally been reserved as a drug of "last resort", used only after treatment with other antibiotics had failed, although the emergence of...
. With the increase of staphylococcal resistance to methicillin
Methicillin
Meticillin or methicillin is a narrow-spectrum beta-lactam antibiotic of the penicillin class. It should not be confused with the antibiotic metacycline.-History:Methicillin was developed by Beecham in 1959...
, vancomycin (or another glycopeptide antibiotic, teicoplanin
Teicoplanin
Teicoplanin is an antibiotic used in the prophylaxis and treatment of serious infections caused by Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and Enterococcus faecalis. It is a glycopeptide antibiotic extracted from Actinoplanes teichomyceticus, with a similar...
) is often a treatment of choice in infections with methicillin-resistant S. aureus
Methicillin-resistant Staphylococcus aureus
Methicillin-resistant Staphylococcus aureus is a bacterium responsible for several difficult-to-treat infections in humans. It is also called multidrug-resistant Staphylococcus aureus and oxacillin-resistant Staphylococcus aureus...
(MRSA). Three classes of vancomycin-resistant S. aureus have emerged that differ in vancomycin susceptibilities
Minimum inhibitory concentration
In microbiology, minimum inhibitory concentration is the lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation. Minimum inhibitory concentrations are important in diagnostic laboratories to confirm resistance of microorganisms...
: vancomycin-intermediate S. aureus (VISA), heterogenous vancomycin-intermediate S. aureus (hVISA), and high-level vancomycin-resistant S. aureus (VRSA).
High-level vancomycin resistance in S. aureus has been rarely reported. However, these strains may also be resistant to meropenem
Meropenem
Meropenem is an ultra-broad spectrum injectable antibiotic used to treat a wide variety of infections, including meningitis and pneumonia. It is a beta-lactam and belongs to the subgroup of carbapenem, similar to imipenem and ertapenem. Meropenem was originally developed by Sumitomo Pharmaceuticals...
and imipenem
Imipenem
Imipenem is an intravenous β-lactam antibiotic developed in 1980. It has an extremely broad spectrum of activity.Imipenem belongs to the subgroup of carbapenems. It is derived from a compound called thienamycin, which is produced by the bacterium Streptomyces cattleya...
, two other antibiotics that can be used in sensitive Staphylococcus strains.
Vancomycin-intermediate S. aureus (VISA)
VISA was first identified in JapanJapan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
in 1996 and has since been found in hospitals in the United Kingdom, France
France
The French Republic , The French Republic , The French Republic , (commonly known as France , is a unitary semi-presidential republic in Western Europe with several overseas territories and islands located on other continents and in the Indian, Pacific, and Atlantic oceans. Metropolitan France...
, the U.S.
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
, Asia
Asia
Asia is the world's largest and most populous continent, located primarily in the eastern and northern hemispheres. It covers 8.7% of the Earth's total surface area and with approximately 3.879 billion people, it hosts 60% of the world's current human population...
, and Brazil
Brazil
Brazil , officially the Federative Republic of Brazil , is the largest country in South America. It is the world's fifth largest country, both by geographical area and by population with over 192 million people...
. 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.
Even with the absence of high-level resistance to vancomycin, another concern posed by the presence of VISA is the increased difficulty in prescribing treatments, especially in situations where an effective treatment for an infection is needed urgently, before detailed resistance profiles can be obtained. In hospitals already endemic with multiresistant
Multidrug resistance
Multiple drug resistance or Multidrug resistance is a condition enabling a disease-causing organism to resist distinct drugs or chemicals of a wide variety of structure and function targeted at eradicating the organism...
MRSA, the appearance of VRSA would make the treatment of infected patients much more difficult.
Treatment
CeftobiproleCeftobiprole
Ceftobiprole is a 4th generation cephalosporin antibiotic with activity against methicillin-resistant Staphylococcus aureus, penicillin-resistant Streptococcus pneumoniae, Pseudomonas aeruginosa, and Enterococci. It was discovered by Basilea Pharmaceutica and was developed by Johnson & Johnson...
was found by Rockefeller University
Rockefeller University
The Rockefeller University is a private university offering postgraduate and postdoctoral education. It has a strong concentration in the biological sciences. It is also known for producing numerous Nobel laureates...
to be effective as of 2008. Linezolid
Linezolid
Linezolid is a synthetic antibiotic used for the treatment of serious infections caused by Gram-positive bacteria that are resistant to several other antibiotics...
, quinupristin/dalfopristin
Quinupristin/dalfopristin
Quinupristin/dalfopristin is a combination of two antibiotics used to treat infections by staphylococci and by vancomycin-resistant Enterococcus faecium....
, daptomycin
Daptomycin
Daptomycin is a novel lipopeptide antibiotic used in the treatment of certain infections caused by Gram-positive organisms. It is a naturally occurring compound found in the soil saprotroph Streptomyces roseosporus. Its distinct mechanism of action means that it may be useful in treating infections...
and tigecycline
Tigecycline
Tigecycline is a glycylcycline antibiotic developed by Francis Tally and marketed by Wyeth under the brand name Tygacil. It was given a U.S. Food and Drug Administration fast-track approval and was approved on June 17, 2005...
are treatments of consideration.
Vancomycin-resistant S. aureus (VRSA)
Clinical experience suggests that barriers exist to the evolution of endogenous vancomycin resistance in S. aureus, given occasional reports of low-level vancomycin resistance. However, in vitroIn vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
and in vivo
In vivo
In vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...
experiments reported in 1992 demonstrated that vancomycin resistance genes from Enterococcus faecalis
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 and other mammals. It is among the main constituents of some probiotic food supplements. Like other species in the genus...
could be transferred by horizontal gene transfer
Horizontal gene transfer
Horizontal gene transfer , also lateral gene transfer , is any process in which an organism incorporates genetic material from another organism without being the offspring of that organism...
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 was isolated from the catheter tip of a diabetic, renal dialysis patient in Michigan. The isolate contained the mecA gene for methicillin resistance
Methicillin-resistant Staphylococcus aureus
Methicillin-resistant Staphylococcus aureus is a bacterium responsible for several difficult-to-treat infections in humans. It is also called multidrug-resistant Staphylococcus aureus and oxacillin-resistant Staphylococcus aureus...
. Vancomycin MICs
Minimum inhibitory concentration
In microbiology, minimum inhibitory concentration is the lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation. Minimum inhibitory concentrations are important in diagnostic laboratories to confirm resistance of microorganisms...
of the VRSA isolate were consistent with the VanA phenotype of Enterococcus
Enterococcus
Enterococcus is a genus of lactic acid bacteria of the phylum Firmicutes. Enterococci are Gram-positive cocci that often occur in pairs or short chains, and are difficult to distinguish from streptococci on physical characteristics alone. Two species are common commensal organisms in the...
species, and the presence of the vanA gene was confirmed by polymerase chain reaction
Polymerase chain reaction
The polymerase chain reaction is a scientific technique in molecular biology to amplify a single or a few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence....
. The DNA sequence of the VRSA vanA gene was identical to that of a vancomycin-resistant strain of Enterococcus faecalis
Vancomycin-Resistant Enterococcus
Vancomycin-resistant Enterococcus, or vancomycin-resistant enterococci , are bacterial strains of the genus Enterococcus that are resistant to the antibiotic vancomycin. To become VRE, vancomycin-sensitive enterococci typically obtain new DNA in the form of plasmids or transposons which encode...
recovered from the same catheter tip. The vanA gene was later found to be encoded within a transposon
Transposon
Transposable elements are sequences of DNA that can move or transpose themselves to new positions within the genome of a single cell. The mechanism of transposition can be either "copy and paste" or "cut and paste". Transposition can create phenotypically significant mutations and alter the cell's...
located on a plasmid
Plasmid
In microbiology and genetics, a plasmid is a DNA molecule that is separate from, and can replicate independently of, the chromosomal DNA. They are double-stranded and, in many cases, circular...
carried by the VRSA isolate. This transposon, Tn1546, confers vanA-type vancomycin resistance in enterococci.
Since 2002, ten additional VRSA isolates have been reported, eight from the United States, one from Iran, and one from India.
Treatment
Trimethoprim/sulfamethoxazole was shown to have efficacy in treating the first known US case of VRSA. LinezolidLinezolid
Linezolid is a synthetic antibiotic used for the treatment of serious infections caused by Gram-positive bacteria that are resistant to several other antibiotics...
, quinupristin/dalfopristin
Quinupristin/dalfopristin
Quinupristin/dalfopristin is a combination of two antibiotics used to treat infections by staphylococci and by vancomycin-resistant Enterococcus faecium....
and daptomycin
Daptomycin
Daptomycin is a novel lipopeptide antibiotic used in the treatment of certain infections caused by Gram-positive organisms. It is a naturally occurring compound found in the soil saprotroph Streptomyces roseosporus. Its distinct mechanism of action means that it may be useful in treating infections...
are treatments of consideration.
See also
- Methicillin-resistant Staphylococcus aureusMethicillin-resistant Staphylococcus aureusMethicillin-resistant Staphylococcus aureus is a bacterium responsible for several difficult-to-treat infections in humans. It is also called multidrug-resistant Staphylococcus aureus and oxacillin-resistant Staphylococcus aureus...
(MRSA) - Vancomycin-resistant EnterococcusVancomycin-Resistant EnterococcusVancomycin-resistant Enterococcus, or vancomycin-resistant enterococci , are bacterial strains of the genus Enterococcus that are resistant to the antibiotic vancomycin. To become VRE, vancomycin-sensitive enterococci typically obtain new DNA in the form of plasmids or transposons which encode...
(VRE)