Vancomycin-resistant Staphylococcus aureus

Vancomycin-resistant Staphylococcus aureus (VRSA) are strains of Staphylococcus aureus that have acquired resistance to the glycopeptide antibiotic vancomycin.[3] 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.[4] Resistance in VRSA is conferred by the plasmid-mediated vanA gene and operon.[5] 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.[6] 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.[5]

Vancomycin-resistant Staphylococcus aureus
Scanning electron micrograph (SEM) shows a strain of Staphylococcus aureus bacteria taken from a vancomycin-intermediate Staphylococcus aureus (VISA) culture.
SpecialtyMicrobiology
Diagnostic methodDisk diffusion[1]
TreatmentBeta-lactam antibiotic (in combination)[2]

Mechanism of acquired resistance

Vancomycin-resistant Staphylococcus aureus was first reported in the United States in 2002.[5] To date, documented cases of VRSA have acquired resistance through uptake of a vancomycin resistance gene cluster from Enterococcus (i.e. VRE).[7] The acquired mechanism is typically the vanA gene and operon from a plasmid in Enterococcus faecium or Enterococcus faecalis.[5]

This mechanism differs from strains of 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 residues.[8]

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 (MIC) using standard laboratory methods, including disc diffusion, gradient strip diffusion, and automated antimicrobial susceptibility testing systems.[1] Once the MIC is known, resistance is determined by comparing the MIC with established breakpoints [9]

Resistant or "R" designations are assigned based on agreed upon values called breakpoints. Breakpoints are published by 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 Susceptiblity Testing.

Treatment of infection
Rifampicin (Rifampin)

When the minimum inhibitory concentration of vancomycin is > 2 µg/mL, an 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, and quinupristin–dalfopristin. For people with 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, rifampin, linezolid, trimethoprim/sulfamethoxazole, or a beta-lactam antibiotic).[2]

History

Three classes of vancomycin-resistant S. aureus have emerged that differ in vancomycin susceptibilities: vancomycin-intermediate S. aureus (VISA), heterogeneous vancomycin-intermediate S. aureus (hVISA), and high-level vancomycin-resistant S. aureus (VRSA).[10]

Vancomycin-intermediate S. aureus (VISA)

Vancomycin-intermediate S. aureus (VISA) (/ˈviːsə/ or /viːaɪɛseɪ/) was first identified in Japan in 1996[11] and has since been found in hospitals elsewhere in Asia, as well as in the United Kingdom, France, the 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.[12]

S. aureus blood agar

Vancomycin-resistant S. aureus (VRSA)

High-level vancomycin resistance in S. aureus has been rarely reported.[13] In vitro and in vivo experiments reported in 1992 demonstrated that vancomycin resistance genes from Enterococcus faecalis could be transferred by gene transfer to S. aureus, conferring high-level vancomycin resistance to S. aureus.[14] Until 2002 such a genetic transfer was not reported for wild S. aureus strains. In 2002, a VRSA strain (/ˈvɜːrsə/ or /viːɑːrɛseɪ/) was isolated from a patient in Michigan.[15] 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.[16]

As of 2019, 52 VRSA strains have been identified in the United States, India, Iran, Pakistan, Brazil, and Portugal.[17]

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 10−6 colonies or even higher.[18]

See also

References
  1. Loomba, Poonam Sood; Taneja, Juhi; Mishra, Bibhabati (2010-01-01). "Methicillin and Vancomycin Resistant S. aureus in Hospitalized Patients". Journal of Global Infectious Diseases. 2 (3): 275–283. doi:10.4103/0974-777X.68535. ISSN 0974-777X. PMC 2946685. PMID 20927290.
  2. Liu, Catherine; et al. (2011). "Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicillin-Resistant Staphylococcus Aureus Infections in Adults and Children". Clinical Infectious Diseases. 52 (3): e18–e55. doi:10.1093/cid/ciq146. PMID 21208910.
  3. "CDC - VISA / VRSA in Healthcare Settings - HAI". www.cdc.gov. Retrieved 2015-06-11.
  4. Cloeckaert, Axel; Zygmunt, Michel S.; Doublet, Benoît (2017-12-05). "Editorial: Genetics of Acquired Antimicrobial Resistance in Animal and Zoonotic Pathogens". Frontiers in Microbiology. 8. doi:10.3389/fmicb.2017.02428. ISSN 1664-302X. PMC 5723418. PMID 29259602.
  5. McGuinness, Will A.; Malachowa, Natalia; DeLeo, Frank (23 Jun 2017). "Vancomycin Resistance in Staphylococcus aureus". Yale J Biol Med. 90 (2): 269-281. PMID 28656013.
  6. Cong, Yanguang; Yang, Sijin; Rao, Xiancai (January 2020). "Vancomycin resistant Staphylococcus aureus infections: A review of case updating and clinical features". Journal of Advanced Research. 21: 169–176. doi:10.1016/j.jare.2019.10.005. ISSN 2090-1232. PMC 7015472. PMID 32071785.
  7. Chang, Soju; Sievert, Dawn M.; Hageman, Jeffrey C.; Boulton, Matthew L.; Tenover, Fred C.; Downes, Frances Pouch; Shah, Sandip; Rudrik, James T.; Pupp, Guy R. (2003-04-03). "Infection with Vancomycin-Resistant Staphylococcus aureus Containing the vanA Resistance Gene". New England Journal of Medicine. 348 (14): 1342–1347. doi:10.1056/NEJMoa025025. ISSN 0028-4793. PMID 12672861.
  8. Howden, Benjamin P.; Davies, John K.; Johnson, Paul D. R.; Stinear, Timothy P.; Grayson, M. Lindsay (2010-01-01). "Reduced Vancomycin Susceptibility in Staphylococcus aureus, Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications". Clinical Microbiology Reviews. 23 (1): 99–139. doi:10.1128/CMR.00042-09. ISSN 0893-8512. PMC 2806658. PMID 20065327.
  9. CLSI (2023). M100 Performance Standards for Antimicrobial Susceptibility Standards (Report) (33 ed.). Wayne PA: Clinical and Laboratory Standards Institute. p. 8.
  10. Appelbaum PC (November 2007). "Reduced glycopeptide susceptibility in methicillin-resistant Staphylococcus aureus (MRSA)". Int. J. Antimicrob. Agents. 30 (5): 398–408. doi:10.1016/j.ijantimicag.2007.07.011. PMID 17888634.
  11. Hiramatsu, K.; Hanaki, H.; Ino, T.; Yabuta, K.; Oguri, T.; Tenover, F. C. (1997-07-01). "Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility". Journal of Antimicrobial Chemotherapy. 40 (1): 135–136. doi:10.1093/jac/40.1.135. ISSN 0305-7453. PMID 9249217.
  12. Howden BP, Davies JK, Johnson PD, Stinear TP, Grayson ML (Jan 2010). "Reduced vancomycin susceptibility in Staphylococcus aureus, including vancomycin-intermediate and heterogeneous vancomycin-intermediate strains: resistance mechanisms, laboratory detection, and clinical implications". Clin. Microbiol. Rev. 23 (1): 99–139. doi:10.1128/CMR.00042-09. PMC 2806658. PMID 20065327.
  13. Gould IM (December 2010). "VRSA-doomsday superbug or damp squib?". Lancet Infect Dis. 10 (12): 816–8. doi:10.1016/S1473-3099(10)70259-0. PMID 21109164.
  14. Proft, Thomas (2013). Bacterial Toxins: Genetics, Cellular Biology and Practical Applications. Horizon Scientific Press. ISBN 9781908230287.
  15. Amábile-Cuevas, Carlos F. (2007). Antimicrobial Resistance in Bacteria. Horizon Scientific Press. ISBN 9781904933243.
  16. Courvalin P (January 2006). "Vancomycin resistance in gram-positive cocci". Clin. Infect. Dis. 42 Suppl 1: S25–34. doi:10.1086/491711. PMID 16323116.
  17. Cong, Yanguang; Yang, Sijin; Rao, Xiancai (2020). "Vancomycin resistant Staphylococcus aureus infections: A review of case updating and clinical features". J Adv Res. 21: 169-176. doi:10.1016/j.jare.2019.10.005. PMC 7015472. PMID 32071785.
  18. Lu, Yichen; Essex, Max; Roberts, Bryan (2008-04-11). Emerging Infections in Asia. Springer Science & Business Media. ISBN 9780387757216.

Further reading
  • Chang, Soju; Sievert, Dawn M.; Hageman, Jeffrey C.; Boulton, Matthew L.; Tenover, Fred C.; Downes, Frances Pouch; Shah, Sandip; Rudrik, James T.; Pupp, Guy R. (April 3, 2003). "Infection with Vancomycin-Resistant Staphylococcus aureus Containing the vanA Resistance Gene". New England Journal of Medicine. 348 (14): 1342–1347. doi:10.1056/NEJMoa025025. ISSN 0028-4793. PMID 12672861.
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