Introduction:Mupirocin competitively inhibits bacterial isoleucyl transfer-RNA synthetase and inhibit bacterial protein synthesis. Widespread usage and over the counter availability of the drug has resulted in resistance among Staphylococcus species.Objectives:This study aimed to determine the overall prevalence of mupirocin resistance among staphylococci. Correlate clinical significance of mupirocin resistance and its relationship to clinical use.Methods:Consecutive, nonrepetitive, clinical isolates of Staphylococcus aureus (n = 98), and coagulase-negative staphylococci (CoNS) (n = 45) from skin and soft-tissue infections between January 2014 and June 2014 were studied. Antibiotic susceptibility testing was done according to Clinical and Laboratory Standards Institute guidelines. Low- and high-level mupirocin resistance was screened by using 5 µg and 200 µg discs respectively and confirmed by agar dilution. Annual consumption of mupirocin was studied and correlated with resistance.Results:High-level mupirocin resistance was found in 8.2% S. aureus and 15.6% of CoNS, while low-level mupirocin resistance was found in 17% S. aureus and 8.9% CoNS. High-level mupirocin resistance was more common in methicillin-sensitive S. aureus isolates when compared with methicillin-resistant S. aureus isolates (P < 0.05). Mupirocin resistant S. epidermidis were associated with methicillin resistance and constitutive clindamycin resistance.Conclusion:High prevalence of mupirocin resistance was found in the present study. Increased prevalence of mupirocin resistance among community-acquired staphylococci demands the judicious use of the drug in the community.