Editing Vancomycin-resistant Staphylococcus aureus

{{Short description|Antibiotic resistant bacteria}}
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{{lead too short|date=May 2020}}
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{{DISPLAYTITLE:Vancomycin-resistant ''Staphylococcus aureus''}}
{{Infobox medical condition (new)
| name            = Vancomycin-resistant Staphylococcus aureus
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| image           = File:Staphylococcus aureus VISA.jpg
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| caption         = [[Scanning electron micrograph]] (SEM) shows a [[strain (biology)|strain]] of ''[[Staphylococcus aureus]]'' bacteria taken from a [[#vancomycin-intermediate Staphylococcus aureus|vancomycin-intermediate ''Staphylococcus aureus'']] (VISA) culture.
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| diagnosis       = Disk diffusion<ref name=vre/>
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| treatment       = Beta-lactam antibiotic (in combination)<ref name=beta/>
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'''Vancomycin-resistant ''Staphylococcus aureus''''' ('''VRSA''') are strains of ''[[Staphylococcus aureus]]'' that have acquired resistance to the [[glycopeptide antibiotic]] [[vancomycin]].<ref>{{cite web|title = CDC - VISA / VRSA in Healthcare Settings - HAI|url = https://www.cdc.gov/HAI/organisms/visa_vrsa/visa_vrsa.html|website = www.cdc.gov|access-date = 2015-06-11}}</ref> 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.<ref>{{Cite journal |last1=Cloeckaert |first1=Axel |last2=Zygmunt |first2=Michel S. |last3=Doublet |first3=Benoît |date=2017-12-05 |title=Editorial: Genetics of Acquired Antimicrobial Resistance in Animal and Zoonotic Pathogens |journal=Frontiers in Microbiology |volume=8 |page=2428 |doi=10.3389/fmicb.2017.02428 |issn=1664-302X |pmc=5723418 |pmid=29259602 |doi-access=free }}</ref> Resistance in VRSA is conferred by the plasmid-mediated ''vanA'' gene and operon.<ref name=":0" />  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.<ref>{{Cite journal |last1=Cong |first1=Yanguang |last2=Yang |first2=Sijin |last3=Rao |first3=Xiancai |date=January 2020 |title=Vancomycin resistant Staphylococcus aureus infections: A review of case updating and clinical features |journal=Journal of Advanced Research |volume=21 |pages=169–176 |doi=10.1016/j.jare.2019.10.005 |issn=2090-1232 |pmc=7015472 |pmid=32071785}}</ref> 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.<ref name=":0">{{cite journal |last1=McGuinness |first1=Will A. |last2=Malachowa |first2=Natalia |last3=DeLeo |first3=Frank |title=Vancomycin Resistance in Staphylococcus aureus |journal=Yale J Biol Med |date=23 Jun 2017 |volume=90 |issue=2 |pages=269–281 |pmid=28656013 <!--|access-date=2 Jun 2023-->|pmc=5482303 }}</ref>

==Mechanism of acquired resistance==
Vancomycin-resistant ''Staphylococcus aureus'' was first reported in the United States in 2002.<ref name=":0" /> To date, documented cases of VRSA have acquired resistance through uptake of a [[vancomycin]] resistance gene cluster from ''Enterococcus'' (i.e. [[Vancomycin-resistant Enterococcus|VRE]]).<ref>{{cite journal |last1=Chang |first1=Soju |last2=Sievert |first2=Dawn M. |last3=Hageman |first3=Jeffrey C. |last4=Boulton |first4=Matthew L. |last5=Tenover |first5=Fred C. |last6=Downes |first6=Frances Pouch |last7=Shah |first7=Sandip |last8=Rudrik |first8=James T. |last9=Pupp |first9=Guy R. |date=2003-04-03 |title=Infection with Vancomycin-Resistant Staphylococcus aureus Containing the vanA Resistance Gene |journal=New England Journal of Medicine |volume=348 |issue=14 |pages=1342–1347 |doi=10.1056/NEJMoa025025 |issn=0028-4793 |pmid=12672861|doi-access=free }}</ref> The acquired mechanism is typically the ''vanA'' gene and operon from a plasmid in ''Enterococcus faecium'' or ''Enterococcus faecalis''.<ref name=":0" /> 

This mechanism differs from strains of [[#vancomycin-intermediate Staphylococcus aureus|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 dipeptidase|<small>D</small>-ala-<small>D</small>-ala]] residues.<ref>{{cite journal|last1=Howden|first1=Benjamin P.|last2=Davies|first2=John K.|last3=Johnson|first3=Paul D. R.|last4=Stinear|first4=Timothy P.|last5=Grayson|first5=M. Lindsay|date=2010-01-01|title=Reduced Vancomycin Susceptibility in Staphylococcus aureus, Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications|journal=Clinical Microbiology Reviews|volume=23|issue=1|pages=99–139|doi=10.1128/CMR.00042-09|issn=0893-8512|pmc=2806658|pmid=20065327}}</ref>

==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|minimum inhibitory concentration (MIC)]] using standard laboratory methods, including [[Disk diffusion test|disc diffusion]], [[Etest|gradient strip diffusion]], and [[antibiotic sensitivity testing|automated antimicrobial susceptibility testing systems]].<ref name="vre">{{cite journal|last1=Loomba|first1=Poonam Sood|last2=Taneja|first2=Juhi|last3=Mishra|first3=Bibhabati|date=2010-01-01|title=Methicillin and Vancomycin Resistant S. aureus in Hospitalized Patients|journal=Journal of Global Infectious Diseases|volume=2|issue=3|pages=275–283|doi=10.4103/0974-777X.68535|issn=0974-777X|pmid=20927290|pmc=2946685 |doi-access=free }}</ref> Once the MIC is known, resistance is determined by comparing the MIC with established breakpoints.<ref>{{cite report
 | author      = CLSI
 | date        = 2023
 | title       = M100 Performance Standards for Antimicrobial Susceptibility Standards
 | publisher   = Clinical and Laboratory Standards Institute
 | edition     =33
 | location    =Wayne PA
 | page        =8
}}</ref>

Resistant or "R" designations are assigned based on agreed upon values called breakpoints. Breakpoints are published by [[Standards organization|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==
[[File:Rifampicin3Dan.gif|thumb|150 px|[[Rifampicin]] (''Rifampin'')]]
When the [[minimum inhibitory concentration]] of vancomycin is {{nowrap|> 2 µg/mL}}, 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 fosamil|ceftaroline]], and [[Quinupristin/dalfopristin|quinupristin–dalfopristin]]. For people with [[Methicillin-resistant Staphylococcus aureus|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]], [[Rifampicin|rifampin]], [[linezolid]], [[trimethoprim/sulfamethoxazole]], or a [[Β-Lactam|beta-lactam]] antibiotic).<ref name="beta">{{cite journal|title=Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus Aureus Infections in Adults and Children|last= Liu|first=Catherine|year=2011|volume=52|issue=3|pages=e18–e55|doi=10.1093/cid/ciq146|journal=Clinical Infectious Diseases|display-authors=etal|pmid=21208910|doi-access=free}}</ref>

==History==
Three classes of vancomycin-resistant ''S. aureus'' have emerged that differ in vancomycin [[minimum inhibitory concentration|susceptibilities]]: vancomycin-intermediate ''S. aureus'' (VISA), heterogeneous vancomycin-intermediate ''S. aureus'' (hVISA), and high-level vancomycin-resistant ''S. aureus'' (VRSA).<ref name="pmid17888634">{{cite journal |author=Appelbaum PC |title=Reduced glycopeptide susceptibility in methicillin-resistant ''Staphylococcus aureus'' (MRSA) |journal=Int. J. Antimicrob. Agents |volume=30 |issue=5 |pages=398–408 |date=November 2007 |pmid=17888634 |doi=10.1016/j.ijantimicag.2007.07.011 }}</ref>

===Vancomycin-intermediate ''S. aureus'' (VISA)===
Vancomycin-intermediate ''S. aureus'' (VISA) ({{IPAc-en|ˈ|v|iː|s|ə}} or {{IPAc-en|v|iː|aɪ|ɛ|s|eɪ}}) was first identified in [[Japan]] in 1996<ref>{{cite journal|last1=Hiramatsu|first1=K.|last2=Hanaki|first2=H.|last3=Ino|first3=T.|last4=Yabuta|first4=K.|last5=Oguri|first5=T.|last6=Tenover|first6=F. C.|date=1997-07-01|title=Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility.|journal=Journal of Antimicrobial Chemotherapy|language=en|volume=40|issue=1|pages=135–136|doi=10.1093/jac/40.1.135|issn=0305-7453|pmid=9249217|doi-access=free}}</ref> and has since been found in hospitals elsewhere in [[Asia]], as well as in [[the United Kingdom]], [[France]], the [[United States|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.<ref>{{cite journal |vauthors=Howden BP, Davies JK, Johnson PD, Stinear TP, Grayson ML |title=Reduced vancomycin susceptibility in ''Staphylococcus aureus'', including vancomycin-intermediate and heterogeneous vancomycin-intermediate strains: resistance mechanisms, laboratory detection, and clinical implications |journal=Clin. Microbiol. Rev. |date=Jan 2010 | volume=23 |issue=1 |pages=99–139 |doi=10.1128/CMR.00042-09 |pmid=20065327 |pmc=2806658 |url=}}</ref>
[[File:S aureus blood agar.jpg|thumb|''[[Staphylococcus aureus|S. aureus]]'' [[blood agar]]]]

===Vancomycin-resistant ''S. aureus'' (VRSA)===
High-level vancomycin resistance in ''S. aureus'' has rarely been reported.<ref name="pmid21109164">{{cite journal |author=Gould IM |title=VRSA-doomsday superbug or damp squib? |journal=Lancet Infect Dis |volume=10 |issue=12 |pages=816–8 |date=December 2010 |pmid=21109164 |doi=10.1016/S1473-3099(10)70259-0 }}</ref> ''[[In vitro]]'' and ''[[in vivo]]'' experiments reported in 1992 demonstrated that vancomycin resistance genes from ''[[Enterococcus faecalis]]'' could be transferred by [[horizontal gene transfer|gene transfer]] to ''S. aureus'', conferring high-level vancomycin resistance to ''S. aureus''.<ref>{{Cite book|title = Bacterial Toxins: Genetics, Cellular Biology and Practical Applications|url = https://books.google.com/books?id=FdAAAgAAQBAJ&q=vancomycin%2520resistance%2520genes%2520from%2520Enterococcus%2520faecalis%2520could%2520be%2520transferred%2520by%2520horizontal%2520gene%2520transfer%2520to%2520S.%2520aureus%252C%2520conferring%2520high-level%2520vancomycin%2520resistance%2520to%2520S.%2520aureus&pg=PA119|publisher = Horizon Scientific Press|date = 2013|isbn = 9781908230287|first = Thomas|last = Proft}}</ref> Until 2002 such a genetic transfer was not reported for wild ''S. aureus'' strains. In 2002, a VRSA strain ({{IPAc-en|ˈ|v|ɜr|s|ə}} or {{IPAc-en|v|iː|ɑr|ɛ|s|eɪ}}) was isolated from a patient in Michigan.<ref>{{Cite book|title = Antimicrobial Resistance in Bacteria|url = https://books.google.com/books?id=sQ7URquB4YcC&q=Vancomycin-resistant%2520S.%2520aureus%2520%2520%2520horizontal%2520gene%2520transfer&pg=PT45|publisher = Horizon Scientific Press|date = 2007|isbn = 9781904933243|first = Carlos F.|last = Amábile-Cuevas}}</ref> The isolate contained the ''mecA'' gene for [[methicillin-resistant Staphylococcus aureus|methicillin resistance]]. Vancomycin [[minimum inhibitory concentration|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 Enterococcus|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.<ref name="pmid16323116">{{cite journal |author=Courvalin P |title=Vancomycin resistance in gram-positive cocci |journal=Clin. Infect. Dis. |volume=42 |pages=S25–34 |date=January 2006 |issue=Suppl 1 |pmid=16323116 |doi=10.1086/491711 |doi-access=free }}</ref>

As of 2019, 52 VRSA strains have been identified in the United States, India, Iran, Pakistan, Brazil, and Portugal.<ref>{{cite journal |last1=Cong |first1=Yanguang |last2=Yang |first2=Sijin |last3=Rao |first3=Xiancai |title=Vancomycin resistant Staphylococcus aureus infections: A review of case updating and clinical features |journal=J Adv Res |date=2020 |volume=21 |pages=169–176 |doi=10.1016/j.jare.2019.10.005 |pmid=32071785|pmc=7015472 }}</ref>

===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<sup>−6</sup> colonies or even higher.<ref>{{Cite book|title = Emerging Infections in Asia|url = https://books.google.com/books?id=5WKoOibILtkC&q=heterogeneous%2520vancomycin-intermediate%2520S.%2520aureus&pg=PA234|publisher = Springer Science & Business Media|date = 2008-04-11|isbn = 9780387757216|first1 = Yichen|last1 = Lu|first2 = Max|last2 = Essex|first3 = Bryan|last3 = Roberts}}</ref>

==See also==
* [[Drug resistance]]

==References==
{{Reflist}}

==Further reading==
* {{Cite journal|title = Infection with Vancomycin-Resistant ''Staphylococcus aureus'' Containing the vanA Resistance Gene|journal = New England Journal of Medicine|date = April 3, 2003|issn = 0028-4793|pmid = 12672861|pages = 1342–1347|volume = 348|issue = 14|doi = 10.1056/NEJMoa025025|first1 = Soju|last1 = Chang|first2 = Dawn M.|last2 = Sievert|first3 = Jeffrey C.|last3 = Hageman|first4 = Matthew L.|last4 = Boulton|first5 = Fred C.|last5 = Tenover|first6 = Frances Pouch|last6 = Downes|first7 = Sandip|last7 = Shah|first8 = James T.|last8 = Rudrik|first9 = Guy R.|last9 = Pupp|doi-access = free}}
== External links ==
* [https://www.ncbi.nlm.nih.gov/pubmed/ PubMed]
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{{DEFAULTSORT:Vancomycin-Resistant Staphylococcus Aureus}}
[[Category:Staphylococcaceae]]
[[Category:Bacterial diseases]]
[[Category:Antibiotic-resistant bacteria]]
[[Category:Staphylococcus]]