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LRE and LR-VRE

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Linezolid-resistant enterococci (LRE) and linezolid-resistant vancomycin-resistant enterococci (LR-VRE) 

Linezolid-resistant enterococci (LRE) and linezolid-resistant vancomycin-resistant enterococci (LR-VRE) are emerging as significant concerns in healthcare settings. These resistant strains pose challenges for treatment and infection control. Linezolid-resistant Enterococci (LRE): 

  • Enterococci are typically found in the intestines and female genital tract but can cause infections, particularly in immunocompromised individuals. 
  • Linezolid, used to treat Gram-positive infections, is ineffective against LRE due to mutations in the 23S rRNA gene (especially G2576T mutation), which prevents the antibiotic from binding to its target and inhibiting protein synthesis. 
  • LRE can be found in species like E. faecalis, E. faecium, E. casseliflavus, E. hirae, E. mundtii, and E. gallinarum. 
  • Infections with LRE are challenging to treat, and resistance can spread quickly in healthcare settings. 

Linezolid-resistant Vancomycin-resistant Enterococci (LRVRE): 

  • Vancomycin-resistant enterococci (VRE) are resistant to vancomycin, a critical antibiotic for Gram-positive infections. 
  • Some VRE strains have also developed resistance to linezolid, creating a significant concern for treatment of these multi-drug-resistant bacteria. 
  • Vancomycin resistance is typically mediated by vanA or vanB genes, which alter the bacterial cell wall, preventing vancomycin binding. 
  • LRVRE strains are particularly problematic in treating serious infections, such as bloodstream infections, urinary tract infections, and endocarditis, due to their dual resistance to both vancomycin and linezolid. 

Risk Factors and Challenges: 

  • Risk factors for acquiring LRE or LRVRE include previous linezolid exposure, prolonged hospitalisation, and immunosuppression. 
  • Infections caused by these strains lead to increased mortality, longer hospital stays, and limited treatment options. 
  • Accurate detection can be difficult, as some isolates may appear susceptible in routine tests but harbor resistance genes. A combination of genotypic and phenotypic assessments is recommended. 

Clinical Impact: 

  • Treatment options for LRE and LRVRE are limited, with alternatives like daptomycin, tigecycline, and quinupristin-dalfopristin required in some cases. However, resistance to these options is also emerging. 
  • These infections are commonly found in hospitalised persons, especially those in intensive care units, due to the increased use of broad-spectrum antibiotics and invasive devices. 

Control Measures: 

  • Prevention strategies include strict hand hygiene, strong infection control practices, antibiotic stewardship programs, and the development of new antimicrobial agents. 
  • Improved surveillance, accurate detection, and constant reporting are essential for tracking their prevalence and guide treatment strategies.  

References: 

  1. Lillian Abbo, Bhavarth S Shukla, Amber Giles & Laura Aragon. (2018). Linezolid and Vancomycin-Resistant Enterococcus faecium in Solid Organ Transplant Recipients: Infection Control and Antimicrobial Stewardship Using Whole Genome Sequencing. Clinical Infectious Diseases 69:2. DOI:10.1093/cid/ciy903 
  2. Maria-Anna Misiakou​, Frederik Boetius Hertz​, Kristian Schønning​, Susanne Häussler & Karen Leth Nielsen. (2023). Emergence of linezolid-resistant Enterococcus faecium in a tertiary hospital in Copenhagen. Microbial Genomics. Volume 7, Issue 7. https://doi.org/10.1099/mgen.0.001055 
  3. Ruru Bi, Tingting Qin, Wenting Fan, Ping Ma & Bing Gu. (2018). The emerging problem of linezolid-resistant enterococci. Global Antimicrobial Resistance. Issue 13, pg. 11-19. 
  4. doi: 10.1016/j.jgar.2017.10.018.  
  5. Sarah A Egan, Anna C Shore, Brian O’Connell, Grainne I Brennan, David C Coleman. (2020). Linezolid resistance in Enterococcus faecium and Enterococcus faecalis from hospitalized patients in Ireland: high prevalence of the MDR genes optrA and poxtA in isolates with diverse genetic backgrounds. Journal of Antimicrobial Chemotherapy, Volume 75, Issue 7, pg. 1704-1711.   https://doi.org/10.1093/jac/dkaa075 
  6. Shakeel Mowlaboccus, Denise A. Daley, Geoffrey W, Coombs. (2023). Genomic characterisation of linezolid-resistant Enterococcus faecalis from Western Australia 2016–2021. The Journal of the Royal college of Pathologists of Australasia. Volume 55, Issue 3, pg. 397-399. https://www.pathologyjournal.rcpa.edu.au/article/S0031-3025(22)00223-9/fulltext 
  7. Ziran Wang, Danping Liu, Jingjia Zhang, Lingli Liu, Zeming Zhang, Chang Liu, Songnian Hu, Linhuan Wu, Zilong He & Hongli Sun.  (2024). Genomic epidemiology reveals multiple mechanisms of linezolid resistance in clinical enterococci in China. Annals of Clinical Microbiology and Antimicrobials. Volume 23, Issue 41.  https://doi.org/10.1186/s12941-024-00689-0