BACTERIOLOGYDecreased vancomycin susceptibility among Staphylococcus aureus clinical isolates and postulated platforms to explore rational drugsAl-Marzoqi, Ali H.a; Kareem, Sawsan M.b; Alhuchaimi, Sundusc; Kadhim Hindi, Nada K.d; Ghasemian, AbdolmajideAuthor Information aDepartment of Biology, College of Science for Women Babylon University Hillah, Hillah bBiology Department, College of Science, Mustansiryah University, Baghdad cDepartment of Microbiology, University of Kufa, Najaf dDepartment of Basic and Medical Science, College of Nursing, Babylon University, Hillah, Iraq eDepartment of Microbiology, Fasa University of Medical Sciences, Fasa, Iran. Correspondence to Abdolmajid Ghasemian, Department of Microbiology, Fasa University of Medical Sciences, Fasa, Iran. Tel: +98 9106806917; e-mail: firstname.lastname@example.org Received 18 February, 2019 Revised 25 October, 2019 Accepted 26 November, 2019 Reviews in Medical Microbiology: July 2020 - Volume 31 - Issue 3 - p 111-116 doi: 10.1097/MRM.0000000000000204 Buy Metrics Abstract Vancomycin is among last-resort drugs for the elimination of serious methicillin-resistant Staphylococcus aureus (MRSA) infections. Suboptimal or prolonged exposure to vancomycin is a major cause of decreased vancomycin susceptibility being a great concern toward the eradication of related infections. This arises from genetic and metabolic alterations leading to cell wall thickness and mitigation of autolysis. Therefore, the study on the major mechanisms contributing to the development of heterogeneous vancomycin-intermediate S. aureus (hVISA) and VISA strains and development of novel and efficient therapeutic approaches is essential. This nonsusceptibility imposes a fitness burden on bacterial cells through adaptive changes not verified entirely. Cell wall thickening and expression of various cell wall-related enzymes are major mechanisms with this regard. Metabolic changes permit growth of VISA in the presence of vancomycin. Prolonged vancomycin consumption, previous MRSA colonization, hemodialysis dependence, residence in an ICU and use of indwelling devices account for major risk factors for VISA emergence, hence care should be taken to hinder their development. Inhibitors of amino sugar and purine biosynthesis have exhibited synergistic properties to kill VISA, postulating the efficiency of combination therapies. In addition, combination of vancomycin with each of metabolic inhibitors, β-lactams (mostly such as fosfomycin, cefazolin, cefepime, ceftaroline, nafcillin, meropenem and piperacillin-tazobactam) have been effective against VISA and hVISA. Combination therapy of MRSA and hVISA with vancomycin and non-β-lactams has exerted lower effects compared to β-lactams combination therapies. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.