{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T01:05:57Z","timestamp":1788570357899,"version":"build-2803163510"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2015,2,1]],"date-time":"2015-02-01T00:00:00Z","timestamp":1422748800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Drug combinations consisting of the DNA intercalating benzophenanthridine alkaloid sanguinarine, the chelator EDTA with the antibiotic streptomycin were tested against several Gram-positive and Gram-negative bacteria, including multi-resistant clinical isolates.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Microdilution, checkerboard and time kill curve methods were used to investigate the antibacterial activity of the individual drugs and the potential synergistic activity of combinations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Key findings<\/jats:title>\n                  <jats:p>Sanguinarine demonstrated a strong activity against Gram-positive and Gram-negative bacteria (minimum inhibitory concentrations, MIC = 0.5\u2013128 \u03bcg\/ml), while streptomycin was active against Gram-negative strains (MIC = 2\u2013128 \u03bcg\/ml). EDTA showed only bacteriostatic activity. Indifference to synergistic activity was seen in the two-drug combinations sanguinarine + EDTA and sanguinarine + streptomycin (fractional inhibitory concentration index = 0.1\u20131.5), while the three-drug combination of sanguinarine + EDTA + streptomycin showed synergistic activity against almost all the strains (except methicillin-resistant Staphylococcus aureus), as well as a strong reduction in the effective doses (dose reduction index = 2\u201316 times) of sanguinarine, EDTA and streptomycin. In time kill studies, a substantial synergistic interaction of the three-drug combination was detected against Escherichia coli and Klebsiella pneumoniae.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The combination of drugs, which interfere with different molecular targets, can be an important strategy to combat multidrug resistant bacteria.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1111\/jphp.12326","type":"journal-article","created":{"date-parts":[[2014,12,10]],"date-time":"2014-12-10T14:59:35Z","timestamp":1418223575000},"page":"264-273","source":"Crossref","is-referenced-by-count":67,"title":["Synergistic antibacterial activity of the combination of the alkaloid sanguinarine with EDTA and the antibiotic streptomycin against multidrug resistant 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