Review Vancomycin-resistant enterococci: Troublemaker of the 21st century Swapnil Ranotkar a,1 , Parveen Kumar b,1, *, Shubhranshu Zutshi a , Krishna Shastrula Prashanth a , Babul Bezbaruah c , Jay Anand b , Mangala Lahkar c a Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), GMCH, Bhangagarh, Guwahati, Assam, India b Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), GMCH, Bhangagarh, Guwahati, Assam, India c Department of Pharmacology, Gauhati Medical College and Hospital (GMCH), Guwahati, Assam, India Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000 2. Why do we care about enterococci?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000 3. Vancomycin: the gold standard . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000 4. Mechanisms of vancomycin resistance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000 5. Epoch of vancomycin-resistant enterococci . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000 6. Evolution of resistance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000 7. Therapeutic alternatives such as chemotherapeutic drugs, herbal strategies and nanotechnology to combat vancomycin-resistant enterococcal infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000 8. Strategies to prevent the spread of vancomycin-resistant enterococci . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000 9. Restriction and development: a balancing act . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000 10. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000 Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000 Journal of Global Antimicrobial Resistance xxx (2014) xxx–xxx A R T I C L E I N F O Article history: Received 18 December 2013 Received in revised form 3 April 2014 Accepted 9 April 2014 Keywords: Enterococci Resistance Vancomycin-resistant enterococci Nosocomial transmission A B S T R A C T The emergence of multidrug-resistant and vancomycin-resistant enterococci during the last decade has made it difficult to treat nosocomial infections. Although various enterococcal species have been identified, only two (Enterococcus faecalis and Enterococcus faecium) are responsible for the majority of human infections. Vancomycin is an important therapeutic alternative against multidrug-resistant enterococci but is associated with a poor prognosis. Resistance to vancomycin dramatically reduces the therapeutic options for enterococcal infections. The bacterium develops resistance by modifying the C- terminal D-alanine of peptidoglycan to D-lactate, creating a D-Ala-D-Lac sequence that effectively reduces the affinity of vancomycin for the peptidoglycan by 1000-fold. Moreover, the resistance genes can be transferred from enterococci to Staphylococcus aureus, thereby posing a threat to patient safety and also a challenge for treating physicians. Judicious use of vancomycin and broad-spectrum antibiotics must be implemented, but strict infection control measures must also be followed to prevent nosocomial transmission of these organisms. Furthermore, improvements in clinical practice, rotation of antibiotics, herbal drugs, nanoantibiotics and the development of newer antibiotics based on a pharmacogenomic approach may prove helpful to overcome dreadful vancomycin-resistant enterococcal infections. ß 2014 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved. * Corresponding author. Present address: Laboratory of Molecular Pharmacology and Toxicology, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), 3rd Floor, Department of Pharmacology, NIPER Guwahati, GMCH, Bhangagarh, Guwahati, Assam 781032, India. Tel.: +91 98 6473 6537; fax: +91 3612337700. E-mail addresses: parveen5niper@gmail.com, parveen.bhuwal@rediffmail.com (P. Kumar). 1 These authors contributed equally to this manuscript. G Model JGAR-86; No. of Pages 8 Please cite this article in press as: Ranotkar S, et al. Vancomycin-resistant enterococci: Troublemaker of the 21st century. J Global Antimicrob Resist (2014), http://dx.doi.org/10.1016/j.jgar.2014.04.002 Contents lists available at ScienceDirect Journal of Global Antimicrobial Resistance jo u rn al h om ep age: w ww.els evier.c o m/lo c ate/jg ar http://dx.doi.org/10.1016/j.jgar.2014.04.002 2213-7165/ß 2014 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.