PurposeThe Centers for Disease Control and Prevention has classified methicillin-resistant S aureus (MRSA) as a serious public health threat. The escalating minimum inhibitory concentration (MIC) of standard anti-methicillin-resistant S aureus (MRSA) drugs within the susceptible range, known as "MIC creep," jeopardizes their effectiveness against MRSA infections, posing additional challenges in managing MRSA infections. This cross-sectional study was conducted in a tertiary care hospital in Central India to assess the susceptibility trends of clinical MRSA isolates against commonly used anti-MRSA drugs and to observe MIC creep, if any, over three years (2020–2022). MethodsThe study included 158 non-repetitive clinical MRSA isolates. The MICs of vancomycin, teicoplanin, and linezolid were determined in MRSA strains using agar dilution, while the MIC of daptomycin was performed by broth microdilution. MIC creep was assessed by calculating MIC50, MIC90, Modal MIC, G-mean MIC, and susceptible and resistant percentages for the fiscal years 2020, 2021, and 2022. ResultsOf the 158 MRSA isolates, none were resistant to vancomycin, teicoplanin, and daptomycin, but two showed resistance to linezolid (LRSA). However, fifteen isolates showed intermediate resistance to vancomycin (VISA), and five showed intermediate resistance to teicoplanin (TISA). MIC of these anti-MRSA drugs increased in 2021 and 2022 compared to 2020. G-mean MIC for vancomycin, teicoplanin, and linezolid in MRSA strains increased significantly over the study period, while daptomycin MIC remained relatively stable, with a slight increase in 2021 and 2022. There was a high resistance rate for clindamycin, doxycycline, and chloramphenicol among VISA, TISA, and LRSA isolates compared to MRSA. ConclusionsDuring the three years of the study, “MIC creep” was observed in vancomycin, teicoplanin, and linezolid and, to some extent, for daptomycin in MRSA strains. The recovery of VISA, TISA, and linezolid-resistant MRSAs is worrisome, suggesting possible MRSA treatment failure and being a forerunner of resistant strains.