The Risk of Emerging Resistance to Trimethoprim/Sulfamethoxazole in Staphylococcus aureus

OBJECTIVE: Due to the spread of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), the demand for trimethoprim/sulfamethoxazole (SXT) is increasing in the world. It is not clear whether the resistant strain emerges by overuse of SXT. We investigated here the emergent risk of the SXT-resistant mutant in S. aureus by an in vitro SXT exposure experiment. METHODS: A total of 40 S. aureus clinical isolates (20 MSSA and 20 MRSA isolates) were exposed to sub-MIC of SXT for consecutive days, and MIC of SXT was determined every day. In addition, the dfrB DNA sequencing was performed to detect the mutation in the SXT-resistant strain. RESULTS: The SXT-resistant strain began to emerge on the eighth day and accounted for 45% (18/40 clinical isolates) after 14 days. Moreover, one half of these resistant strains showed F98Y mutation in DfrB to retain SXT-resistance without selective pressure. CONCLUSION: The emergent risk was SXT exposure of 14 days or more.