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The recommended therapy has been often failure through the interfering of beta-lactamase-producing bacteria (BLPB). The present study was to investigate antibacterial activity, synergy, and modes of action of luteolin and quercetin using alone and plus ceftazidime against<jats:italic>S. pyogenes<\/jats:italic>. The MICs of ceftazidime, luteolin, and quercetin against all<jats:italic>S. pyogenes<\/jats:italic>were 0.50, 128, and 128\u2009<jats:italic>\u00b5<\/jats:italic>g\u2009mL<jats:sup>\u22121<\/jats:sup>, respectively. A synergistic effect was exhibited on luteolin and quercetin plus ceftazidime against these strains at fractional inhibitory concentration indices 0.37 and 0.27, respectively, and was confirmed by the viable count. These combinations increased cytoplasmic membrane (CM) permeability, caused irregular cell shape, peptidoglycan, and CM damage, and decreased nucleic acid but increased proteins in bacterial cells. Enzyme assay demonstrated that these flavonoids had an inhibitory activity against<jats:italic>\u03b2<\/jats:italic>-lactamase. In summary, this study provides evidence that the inhibitory mode of action of luteolin and quercetin may be mediated via three mechanisms: (1) inhibiting of peptidoglycan synthesis, (2) increasing CM permeability, and (3) decreasing nucleic acid but increasing the protein contents of bacterial cells. So, luteolin and quercetin propose the high potential to develop adjunct to ceftazidime for the treatment of coexistence of the BLPB and<jats:italic>S. pyogenes<\/jats:italic>infections.<\/jats:p>","DOI":"10.1155\/2015\/759459","type":"journal-article","created":{"date-parts":[[2015,10,22]],"date-time":"2015-10-22T14:56:36Z","timestamp":1445525796000},"page":"1-12","source":"Crossref","is-referenced-by-count":60,"title":["Synergy and Mode of Action of Ceftazidime plus Quercetin or Luteolin on<i>Streptococcus pyogenes<\/i>"],"prefix":"10.1155","volume":"2015","author":[{"given":"Supatcharee","family":"Siriwong","sequence":"first","affiliation":[{"name":"School of Pharmacology, Institute of Science, Suranaree University of Technology, 111 University Avenue, Suranaree Subdistrict, Muang District, Nakhon Ratchasima 30000, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanjana","family":"Thumanu","sequence":"additional","affiliation":[{"name":"Synchrotron Light 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