Tehran University of Medical Sciences Iranian Journal of Microbiology 2008-3289 9 4 2017 11 15 208 212 EN Nagalakshmi Narasimhaswamy Department of Microbiology, Melaka Manipal Medical College (Manipal Campus) Manipal University, Manipal, Karnataka 576104, India Indira Bairy Department of Microbiology, Melaka Manipal Medical College (Manipal Campus) Manipal University, Manipal, Karnataka 576104, India Gautham Shenoy Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India Laxminarayana Bairy Department of Pharmacology, RAK Medical and Health Sciences University, Ras Al Khaimah, UAE 2017 02 14 2017 07 20 Background and Objectives: The antimicrobial combination with synergistic mechanism is recommended to provide broad-spectrum coverage, and prevent the emergence of resistant mutants. In the present study, the synergistic activity of lysostaphin with linezolid, oxacillin and vancomycin, against methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates was determined. Materials and Methods: Seventy-three MRSA isolates collected from clinical specimens were tested, for in vitro synergistic activity of lysostaphin with linezolid, vancomycin and oxacillin, by checkerboard assay.  Results: Lysostaphin showed synergistic activity with linezolid and oxacillin, against all MRSA isolates, tested in the present study. Whereas, only 19.1% of the isolates showed synergistic activity with vancomycin and remaining 80.9% of the MRSA isolates showed additive activity. Conclusion: Lysostaphin causes rapid lysis of S. aureus. Combination therapies that include linezolid and lysostaphin could be used in life-threatening infections, such as endocarditis to increase the early in vivo activity of the antibiotics, and to prevent the emergence of linezolid resistant mutants. Further, in vivo studies are warranted to confirm our results. https://ijm.tums.ac.ir/index.php/ijm/article/view/1285 https://ijm.tums.ac.ir/index.php/ijm/article/download/1285/739