vancomycin-resistant Enterococcus

{{short description|Bacterial strains of Enterococcus that are resistant to the antibiotic vancomycin}}

{{cs1 config|name-list-style=vanc}}

{{DISPLAYTITLE:Vancomycin-resistant Enterococcus}}

{{Infobox medical condition (new)

| name = Vancomycin-resistant Enterococcus

| synonyms = Vancomycin-resistant enterococci

| image = Vancomycin-Resistant Enterococcus 01.jpg

| alt =

| caption = SEM micrograph of vancomycin-resistant enterococci

| pronounce =

| field = Microbiology

| symptoms =

| complications =

| onset =

| duration =

| types =

| causes =

| risks =

| diagnosis =

| differential =

| prevention = Screen with peri-rectal swab

| treatment = Linezolid

| medication =

| prognosis =

| frequency =

| deaths =

}}

Vancomycin-resistant Enterococcus, or vancomycin-resistant enterococci (VRE), are bacterial strains of the genus Enterococcus that are resistant to the antibiotic vancomycin.{{cite web |title = Vancomycin-resistant Enterococci (VRE) in Healthcare Settings |publisher = CDC |work = VRE in Healthcare Settings - HAI |url = https://www.cdc.gov/HAI/organisms/vre/vre.html |access-date = 2015-06-09 |archive-date = 2019-05-18 |archive-url = https://web.archive.org/web/20190518191817/https://www.cdc.gov/hai/organisms/vre/vre.html |url-status = live }}

Mechanism of acquired resistance

File:Vancomycin-from-xtal-1996-3D-balls.png

Six different types of vancomycin resistance are shown by enterococcus: Van-A, Van-B, Van-C, Van-D, Van-E and Van-G.{{cite book|title = Antimicrobial Resistance and Implications for the 21st Century|url = https://books.google.com/books?id=E4JuhqT9JzgC&q=different%252520types%252520of%252520vancomycin%252520resistance%252520are%252520shown%252520by%252520enterococcus%252520%25253A%252520Van-A%25252C%252520Van-B%25252C%252520Van-C%25252C%252520Van-D%25252C%252520Van-E%252520and%252520Van-F&pg=PA26|publisher = Springer Science & Business Media|date = 2007-11-15|isbn = 9780387724188|first1 = I. W.|last1 = Fong|first2 = Karl|last2 = Drlica|access-date = 2020-12-17|archive-date = 2023-01-14|archive-url = https://web.archive.org/web/20230114092651/https://books.google.com/books?id=E4JuhqT9JzgC&q=different%252520types%252520of%252520vancomycin%252520resistance%252520are%252520shown%252520by%252520enterococcus%252520%25253A%252520Van-A%25252C%252520Van-B%25252C%252520Van-C%25252C%252520Van-D%25252C%252520Van-E%252520and%252520Van-F&pg=PA26|url-status = live}} The significance is that Van-A VRE is resistant to both vancomycin and teicoplanin,{{cite book|title = Science and Technology Against Microbial Pathogens: Research, Development and Evaluation, Proceedings of the International Conference on Antimicrobial Research (ICAR2010), Valladolid, Spain 3 - 5 November 2010|url = https://books.google.com/books?id=cVAft_EP8kUC&q=Van-A%252520VRE%252520is%252520resistant%252520to%252520both%252520vancomycin%252520and%252520teicoplanin%25252C&pg=PA360|publisher = World Scientific|date = 2011|isbn = 9789814354868|first = A.|last = Mendez-Vilas}} Van-B VRE is resistant to vancomycin but susceptible to teicoplanin,{{cite book|title = New Strategies Combating Bacterial Infection|url = https://books.google.com/books?id=Hrdzorisyp8C&q=Van%252520B%252520susceptible%252520to%252520teicoplanin&pg=PA17|publisher = John Wiley & Sons|date = 2008-11-21|isbn = 9783527622948|first1 = Iqbal|last1 = Ahmad|first2 = Farrukh|last2 = Aqil}}{{cite book|title = Kucers' The Use of Antibiotics Sixth Edition: A Clinical Review of Antibacterial, Antifungal and Antiviral Drugs|url = https://books.google.com/books?id=XR3cBQAAQBAJ&q=Van%252520c%252520is%252520partly%252520resistant%252520susceptible%252520to%252520teicoplanin&pg=PA575|publisher = CRC Press|date = 2010-10-29|isbn = 9781444147520|first1 = M. Lindsay|last1 = Grayson|first2 = Suzanne M.|last2 = Crowe|first3 = James S.|last3 = McCarthy|first4 = John|last4 = Mills|first5 = Johan W.|last5 = Mouton|first6 = S. Ragnar|last6 = Norrby|first7 = David L.|last7 = Paterson|first8 = Michael A.|last8 = Pfaller|access-date = 2020-12-17|archive-date = 2023-01-14|archive-url = https://web.archive.org/web/20230114092651/https://books.google.com/books?id=XR3cBQAAQBAJ&q=Van%252520c%252520is%252520partly%252520resistant%252520susceptible%252520to%252520teicoplanin&pg=PA575|url-status = live}} 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.{{cite journal|title = Figure 4 : The rise of the Enterococcus: beyond vancomycin resistance : Nature Reviews Microbiology|journal = Nature Reviews Microbiology|volume = 10|issue = 4|pages = 266–278|doi = 10.1038/nrmicro2761|pmid = 22421879|pmc = 3621121|year = 2012|last1 = Arias|first1 = Cesar A.|last2 = Murray|first2 = Barbara E.}}

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.{{cite journal|title = Structural and Functional Characterization of VanG d-Ala:d-Ser Ligase Associated with Vancomycin Resistance in Enterococcus faecalis♦|journal = The Journal of Biological Chemistry|date = 2012|issn = 0021-9258|pmc = 3488035|pmid = 22969085|pages = 37583–37592|volume = 287|issue = 45|doi = 10.1074/jbc.M112.405522|first1 = Djalal|last1 = Meziane-Cherif|first2 = Frederick A.|last2 = Saul|first3 = Ahmed|last3 = Haouz|first4 = Patrice|last4 = Courvalin| doi-access=free }}{{cite book|title = Antibiotic Resistance|url = https://books.google.com/books?id=Zctja6ZwaccC&q=The%252520D-alanyl-D-lactate%252520variation%252520%252520%252520vancomycin&pg=PA48|publisher = Springer Science & Business Media|date = 2012-08-31|isbn = 9783642289507|first = Anthony R. M.|last = Coates|access-date = 2020-12-17|archive-date = 2023-01-14|archive-url = https://web.archive.org/web/20230114092716/https://books.google.com/books?id=Zctja6ZwaccC&q=The%252520D-alanyl-D-lactate%252520variation%252520%252520%252520vancomycin&pg=PA48|url-status = live}}

{{clear}}

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.{{cite book|title = Infection Prevention and Control: Applied Microbiology for Healthcare|url = https://books.google.com/books?id=pv4cBQAAQBAJ&q=vancomycin%252520resistant%252520enterococcus%252520occurs%252520new%252520plasmids&pg=PA17|publisher = Palgrave Macmillan|date = 2008-08-20|isbn = 9781137045928|first1 = Dinah|last1 = Gould|first2 = Christine|last2 = Brooker}}{{Dead link|date=March 2024 |bot=InternetArchiveBot |fix-attempted=yes }} This acquired vancomycin resistance is distinguished from the natural vancomycin resistance of certain enterococcal species including E. gallinarum and E. {{Not a typo|casseliflavus/flavescens}}.{{cite journal |vauthors=Monticelli J, etal |title=Clinical management of non-faecium non-faecalis vancomycin-resistant enterococci infection. Focus on Enterococcus gallinarum and Enterococcus casseliflavus/flavescens. |journal=J Infect Chemother |date=2018 |volume=24 |issue=4 |pages=237–246 |doi=10.1016/j.jiac.2018.01.001 |pmid=29396199|doi-access=free }}{{cite web |title = VRE and the Clinical Laboratory - HAI |work = Healthcare-associated Infections |url = https://www.cdc.gov/HAI/settings/lab/VREClinical-Laboratory.html |publisher = CDC |access-date = 2015-06-09 |archive-date = 2019-04-14 |archive-url = https://web.archive.org/web/20190414012519/https://www.cdc.gov/hai/settings/lab/vreclinical-laboratory.html |url-status = live }}

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 (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.{{cite web|title=Vancomycin-resistant Enterococci (VRE) and the Clinical Laboratory|url=https://www.cdc.gov/hai/settings/lab/vreclinical-laboratory.html|publisher=Centers for Disease Control and Prevention|access-date=21 May 2017|language=en-us|archive-date=14 April 2019|archive-url=https://web.archive.org/web/20190414012519/https://www.cdc.gov/hai/settings/lab/vreclinical-laboratory.html|url-status=live}} {{PD-notice}} Detection of vancomycin resistance by the use of PCR targeting vanA and vanB can also be performed.{{cite journal |vauthors=Zirakzadeh A, Patel R |title=Vancomycin-resistant enterococci: colonization, infection, detection, and treatment |journal=Mayo Clin Proc |volume=81 |issue=4 |pages=529–36 |date=April 2006 |pmid=16610573 |doi=10.4065/81.4.529 |url=https://www.mayoclinicproceedings.org/article/S0025-6196(11)61901-0/fulltext |quote="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." |access-date=2022-09-11 |archive-date=2022-09-11 |archive-url=https://web.archive.org/web/20220911085210/https://www.mayoclinicproceedings.org/article/S0025-6196(11)61901-0/fulltext |url-status=live }}{{cite journal |vauthors=Holzknecht BJ, Hansen DS, Nielsen L, Kailow A, Jarløv JO |title=Screening for vancomycin-resistant enterococci with Xpert® vanA/vanB: diagnostic accuracy and impact on infection control decision making |journal=New Microbes New Infect |volume=16 |pages=54–59 |date=March 2017 |pmid=28203378 |pmc=5295639 |doi=10.1016/j.nmni.2016.12.020 }}

Once the individual has VRE, it is important to ascertain which strain.{{cite book |last1=Levitus |first1=Matthew |last2=Rewane |first2=Ayesan |last3=Perera |first3=Thomas B. |title=StatPearls |date=2022 |publisher=StatPearls Publishing |url=https://pubmed.ncbi.nlm.nih.gov/30020605/ |access-date=27 March 2022 |chapter=Vancomycin-Resistant Enterococci |pmid=30020605 |archive-date=27 March 2022 |archive-url=https://web.archive.org/web/20220327124113/https://pubmed.ncbi.nlm.nih.gov/30020605/ |url-status=live }}

Treatment of infection

File:Linezolid-from-xtal-2008-3D-balls.png

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.{{cite journal|title = Association of Vancomycin-Resistant Enterococcus Bacteremia and Ceftriaxone Usage|journal = Infection Control and Hospital Epidemiology|date = 2012|issn = 0899-823X|pmc = 3879097|pmid = 22669234|volume = 33|issue = 7|doi = 10.1086/666331|first1 = James A.|last1 = McKinnell|first2 = Danielle F.|last2 = Kunz|first3 = Eric|last3 = Chamot|first4 = Mukesh|last4 = Patel|first5 = Rhett M.|last5 = Shirley|first6 = Stephen A.|last6 = Moser|first7 = John W.|last7 = Baddley|first8 = Peter G.|last8 = Pappas|first9 = Loren G.|last9 = Miller|pages=718–724}} Lactobacillus rhamnosus GG (LGG), a strain of L. rhamnosus, was used successfully for the first time to treat gastrointestinal carriage of VRE.{{cite book|title = Novel Antimicrobial Agents and Strategies|url = https://books.google.com/books?id=BWBhBAAAQBAJ&q=Lactobacillus%252520rhamnosus%252520GG%252520%252520treat%252520%252520VRE&pg=PT226|publisher = John Wiley & Sons|date = 2014-08-25|isbn = 9783527676156|first1 = David A.|last1 = Phoenix|first2 = Frederick|last2 = Harris|first3 = Sarah R.|last3 = Dennison}} In the US, linezolid is commonly used to treat VRE.{{cite journal|title = Systematic Review and Meta-Analysis of Linezolid versus Daptomycin for Treatment of Vancomycin-Resistant Enterococcal Bacteremia|journal = Antimicrobial Agents and Chemotherapy|date =2014|issn = 0066-4804|pmid = 24247127|pages = 734–739|volume = 58|issue = 2|doi = 10.1128/AAC.01289-13|first1 = Eleni P.|last1 = Balli|first2 = Chris A.|last2 = Venetis|first3 = Spiros|last3 = Miyakis|pmc=3910884}} The combination of daptomycin and ampicillin is another option to treat VRE infections, especially for bacteremia.{{cite journal |last1=Werth |first1=Brian J |last2=Barber |first2=Katie E |last3=Tran |first3=Nikki |last4=Nonejuie |first4=P |last5=Sakoulas |first5=G |last6=Pogliano |first6=J |last7=Rybak |first7=Michael J |date=2015-02-01 |title=Ceftobiprole and ampicillin increase daptomycin susceptibility of daptomycin-susceptible and -resistant VRE |url=https://academic.oup.com/jac/article/70/2/489/2911200 |journal=Journal of Antimicrobial Chemotherapy |language=en |volume=70 |issue=2 |pages=489–493 |doi=10.1093/jac/dku386 |pmid=25304643 |issn=0305-7453 |doi-access=free |access-date=2023-10-25 |archive-date=2022-05-08 |archive-url=https://web.archive.org/web/20220508000554/https://academic.oup.com/jac/article/70/2/489/2911200 |url-status=live }} 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.{{cite journal |vauthors=de Oliveira Santos JV, da Costa Júnior SD, de Fátima Ramos Dos Santos Medeiros SM, Cavalcanti ID, de Souza JB, Coriolano DL, da Silva WR, Alves MH, Cavalcanti IM |title=Panorama of Bacterial Infections Caused by Epidemic Resistant Strains |journal=Current Microbiology |volume=79 |issue=6 |pages=175 |date=April 2022 |pmid=35488983 |pmc=9055366 |doi=10.1007/s00284-022-02875-9}} If the VRE strain is vanB, teicoplanin and dalbavancin are suitable therapeutic options.{{cite journal |last1=Riccardi |first1=Niccolò |last2=Monticelli |first2=Jacopo |last3=Antonello |first3=Roberta Maria |last4=Di Lallo |first4=Gustavo |last5=Frezza |first5=Domenico |last6=Luzzati |first6=Roberto |last7=Di Bella |first7=Stefano |date=2021-04-01 |title=Therapeutic Options for Infections Due to vanB Genotype Vancomycin-Resistant Enterococci |url=https://www.liebertpub.com/doi/10.1089/mdr.2020.0171 |journal=Microbial Drug Resistance |language=en |volume=27 |issue=4 |pages=536–545 |doi=10.1089/mdr.2020.0171 |pmid=32799629 |s2cid=221144533 |issn=1076-6294}} 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.{{cite journal |last1=Di Cecco |first1=Caterina |last2=Monticelli |first2=Jacopo |last3=Di Bella |first3=Stefano |last4=Di Maso |first4=Vittorio |last5=Luzzati |first5=Roberto |date=2023-08-21 |title=Vancomycin-resistant enterococcus bloodstream infection successfully managed with oritavancin and fosfomycin as sequential treatment |url=https://www.tandfonline.com/doi/full/10.1080/1120009X.2023.2247205 |journal=Journal of Chemotherapy |volume=36 |issue=1 |language=en |pages=31–34 |doi=10.1080/1120009X.2023.2247205 |pmid=37602423 |s2cid=261048377 |issn=1120-009X |access-date=2023-10-25 |archive-date=2023-08-21 |archive-url=https://web.archive.org/web/20230821155351/https://www.tandfonline.com/doi/full/10.1080/1120009X.2023.2247205 |url-status=live }}

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.{{cite book|title = Bacterial Population Genetics in Infectious Disease|url = https://books.google.com/books?id=MPWJIcTxcyQC&q=E.%252520faecalis%252520and%252520E.%252520faecium%252520%252520%252520vancomycin%252520resistant%2525201980%27s&pg=PA196|publisher = John Wiley & Sons|date = 2010-03-16|isbn = 9780470600115|first1 = D. Ashley|last1 = Robinson|first2 = Edward J.|last2 = Feil|first3 = Daniel|last3 = Falush}}{{cite journal |vauthors=Murray BE |title=Vancomycin-resistant enterococcal infections |journal=N Engl J Med |volume=342 |issue=10 |pages=710–21 |date=March 2000 |pmid=10706902 |doi=10.1056/NEJM200003093421007 |url=https://www.nejm.org/doi/10.1056/NEJM200003093421007 |quote="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." |access-date=2022-09-11 |archive-date=2022-09-11 |archive-url=https://web.archive.org/web/20220911090912/https://www.nejm.org/doi/10.1056/NEJM200003093421007 |url-status=live }} 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.{{cite journal |vauthors=Hidron AI, Edwards JR, Patel J, etal |title=NHSN annual update: antimicrobial-resistant pathogens associated with healthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006-2007 |journal=Infect Control Hosp Epidemiol |volume=29 |issue=11 |pages=996–1011 |date=November 2008 |pmid=18947320 |doi=10.1086/591861 |s2cid=205988392 }} VRE can be carried by healthy people who have come into contact with the bacteria, usually in a hospital{{cite web |title = Diseases and Organisms in Healthcare Settings |work = Healthcare-associated Infections (HAIs) |url = https://www.cdc.gov/HAI/organisms/organisms.html |publisher = CDC |access-date = 2015-06-09 |archive-date = 2015-07-08 |archive-url = https://web.archive.org/web/20150708044509/http://www.cdc.gov/HAI/organisms/organisms.html |url-status = live }} (nosocomial infection),{{cite journal|title = Nosocomial Infections: The Definition Criteria |journal = Iranian Journal of Medical Sciences|date = 2012|pmc = 3470069|pmid = 23115435|pages = 72–73|volume = 37|issue = 2|first1 = Farideh|last1 = Kouchak|first2 = Mehrdad|last2 = Askarian}} although it is thought that a significant percentage of intensively farmed chickens also carry VRE.{{cite journal | title = Vancomycin resistant enterococci in farm animals – occurrence and importance |journal = Infection Ecology & Epidemiology |date = 2012 |pmc = 3426332|pmid = 22957131 |volume = 2 |pages = 16959 |doi = 10.3402/iee.v2i0.16959 | first = Oskar|last = Nilsson|issue = 1 |bibcode = 2012InfEE...216959N }}

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.{{cite journal |title=Frequency of Vancomycin-Resistant Enterococci from Three Hospitals in Iran |journal=Daru |year=2006 |last1=Fathollahzadeh |first1=Bahram |last2=Hashemi |first2=Farhad B. |last3=Emaneini |first3=Mohammad |last4=Aligholi |first4=Marzieh |last5=Nakhjavani |first5=Farrokh A. |volume=14 |issue=3 |pages=141–146 |url=http://daru.tums.ac.ir/index.php/daru/article/download/281/281 |format=PDF |access-date=2015-12-30 |archive-date=2016-03-04 |archive-url=https://web.archive.org/web/20160304081034/http://daru.tums.ac.ir/index.php/daru/article/download/281/281 |url-status=dead }}

See also

References

{{Reflist}}

Further reading

  • {{cite book|title = Prebiotics: Development and Application|url = https://books.google.com/books?id=ZJt03QsoaysC&q=Lactobacillus+rhamnosus+GG++treat++VRE|publisher = John Wiley & Sons|date = 2006-05-01|isbn = 9780470023143|first1 = Bob|last1 = Rastall|first2 = Glenn|last2 = Gibson}}