Abstract
The increasing prevalence of antimicrobial resistance (AMR) in Staphylococcus aureus against commonly used antibiotics is a major global health issue. To prevent the emergence of AMR and maintain the desired therapeutic effect, the use of drug combinations in the therapeutic management of infections can be contemplated. This approach allows for the administration of lower antibiotic dosages without compromising the desired therapeutic outcome. Despite the documented antimicrobial activity of fucoxanthin, a widely recognized marine carotenoid, there are a lack of previous reports exploring its potential to enhance the therapeutic effect of antibiotics. The current study aimed to investigate whether fucoxanthin can inhibit S. aureus including the strains resistant to methicillin and to investigate whether fucoxanthin can enhance the therapeutic effect of cefotaxime, a widely prescribed 3rd-generation cephalosporin β-lactam antibiotic known to exhibit resistance in certain cases. Synergism or additive interactions were determined using checkerboard dilution and isobologram analysis, while bactericidal activity was carried out using the time-kill kinetic assay. It is important to highlight that a synergistic bactericidal effect was observed in all strains of S. aureus when fucoxanthin was combined with cefotaxime at a specific concentration ratio. These findings suggest that fucoxanthin holds promise in enhancing the therapeutic efficacy of cefotaxime.



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Acknowledgements
Authors thanks to Enty Tjoa, MD for the valuable discussion regarding on the microorganism characteristic. Many thanks to technical staffs from the Department of Pharmacy and Department of Microbiology for the laboratory support.
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This work was supported by Atma Jaya Catholic University of Indonesia.
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ADRN contributed to conceptualization, methodology, data analysis, and writing of the original draft, JL contributed to data collection, methodology, formal analysis, and writing, revising, and reviewing of the manuscript, MW contributed to conceptualization, methodology, and writing, reviewing, and revising of the manuscript. All authors contributed to the article and approved the submitted version.
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Nurcahyanti, A.D.R., Lady, J. & Wink, M. Fucoxanthin Potentiates the Bactericidal Activity of Cefotaxime Against Staphylococcus aureus. Curr Microbiol 80, 260 (2023). https://doi.org/10.1007/s00284-023-03381-2
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DOI: https://doi.org/10.1007/s00284-023-03381-2