{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T02:34:39Z","timestamp":1779935679892,"version":"3.53.1"},"reference-count":30,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100020291","name":"Kitasato University School of Allied Health Sciences","doi-asserted-by":"crossref","award":["2021-1046"],"award-info":[{"award-number":["2021-1046"]}],"id":[{"id":"10.13039\/501100020291","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Methicillin-resistant <jats:italic>Staphylococcus aureus<\/jats:italic> (MRSA) is highly drug-resistant. The current Japanese guidelines (2019 edition) for managing and treating MRSA infections mention alternative anti-MRSA agents, including sulfamethoxazole-trimethoprim (ST) and rifampicin (RFP). Both ST and RFP are oral drugs and are expected to be effective alternatives to anti-MRSA drugs in clinical cases where anti-MRSA drugs are not indicated. Although guidelines for treating MRSA infections describe the efficacy of ST-RFP combination therapy and although it is used in clinical practice, only a limited number of <jats:italic>in vitro<\/jats:italic> studies have demonstrated its efficacy in pharmacokinetic\/pharmacodynamic models. This study aimed to investigate the efficacy of the combination therapy of ST-RFP against MRSA in some <jats:italic>in vitro<\/jats:italic> models, including a pharmacokinetic\/pharmacodynamic model. The MRSA strains obtained were subjected to antibiotic susceptibility tests. A checkerboard assay for drug combination synergy of ST-RFP was performed. Furthermore, a chemostat model was used to validate the combination therapy of ST-RFP as an <jats:italic>in vitro<\/jats:italic> pharmacokinetic\/pharmacodynamic model. Viable cell counts and antibiotic concentrations were measured. The checkerboard assay showed that the ST-RFP combination had an additive effect on all strains (the lowest fractional inhibitory concentration index ranged from 0.63 to 1.00). The <jats:italic>in vitro<\/jats:italic> chemostat model demonstrated the usefulness of the combination of ST-RFP against MRSA, especially in ST-resistant strains. Regrowth of MRSA was observed in RFP monotherapy but not in the ST-RFP combination therapy. This study demonstrated the potential effectiveness of the ST-RFP combination against ST-resistant MRSA, providing important foundational data that may support future clinical investigations.<\/jats:p>","DOI":"10.1371\/journal.pone.0323935","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T17:54:26Z","timestamp":1747763666000},"page":"e0323935","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Sulfamethoxazole-trimethoprim plus rifampicin combination therapy for methicillin-resistant Staphylococcus aureus infection: An in vitro 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