{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T14:39:35Z","timestamp":1776091175993,"version":"3.50.1"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2015,5,1]],"date-time":"2015-05-01T00:00:00Z","timestamp":1430438400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Chronic periodontitis is one of the most prevalent human diseases and is caused by dysbiosis of the subgingival microbiota. Treatment involves primarily mechanical disruption of subgingival biofilms and, in certain cases, adjunctive use of systemic antibiotic therapy.<jats:italic>In vitro<\/jats:italic>biofilm models have been developed to study antimicrobial agents targeting subgingival species. However, these models accommodate a limited number of taxa, lack reproducibility, and have low throughput. We aimed to develop an<jats:italic>in vitro<\/jats:italic>multispecies biofilm model that mimics subgingival plaque, to test antimicrobial agents. Biofilms were cultivated using the Calgary Biofilm Device and were exposed to amoxicillin (AMX), metronidazole (MTZ), azithromycin (AZM), and AMX-MTZ at four different concentrations for 12, 24, or 36 h. Chlorhexidine (CHX) (0.12%) was used as the positive control. The compositions of the biofilms were analyzed by checkerboard DNA-DNA hybridization, and the percent reduction in biofilm metabolic activity was determined using 2,3,5-triphenyltetrazolium chloride and spectrophotometry. Thirty-five of the 40 species used in the inoculum were consistently recovered from the resulting<jats:italic>in vitro<\/jats:italic>biofilms. After 36 h of exposure at the 1:27 dilution, AMX-MTZ reduced metabolic activity 11% less than CHX (<jats:italic>q<\/jats:italic>= 0.0207) but 54% more than AMX (<jats:italic>q<\/jats:italic>= 0.0031), 72% more than MTZ (<jats:italic>q<\/jats:italic>= 0.0031), and 67% more than AZM (<jats:italic>q<\/jats:italic>= 0.0008). Preliminary evidence of a synergistic interaction between AMX and MTZ was also observed. In summary, we developed reproducible biofilms with 35 subgingival bacterial species, and our results suggested that the combination of AMX and MTZ had greater antimicrobial effects on these<jats:italic>in vitro<\/jats:italic>multispecies biofilms than expected on the basis of the independent effects of the drugs.<\/jats:p>","DOI":"10.1128\/aac.04974-14","type":"journal-article","created":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T03:43:50Z","timestamp":1425354230000},"page":"2791-2798","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":47,"title":["Effects of Azithromycin, Metronidazole, Amoxicillin, and Metronidazole plus Amoxicillin on an<i>In Vitro<\/i>Polymicrobial Subgingival Biofilm Model"],"prefix":"10.1128","volume":"59","author":[{"given":"Geisla M. S.","family":"Soares","sequence":"first","affiliation":[{"name":"Dental Research Division, Department of Periodontology, Guarulhos University, Guarulhos, S\u00e3o Paulo, Brazil"},{"name":"Department of Applied Oral Science, Forsyth Institute, Cambridge, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flavia","family":"Teles","sequence":"additional","affiliation":[{"name":"Department of Periodontology, University of North Carolina School of Dentistry, Chapel Hill, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacqueline R.","family":"Starr","sequence":"additional","affiliation":[{"name":"Department of Applied Oral Science, Forsyth Institute, Cambridge, Massachusetts, USA"},{"name":"Department of Oral Health Policy and Epidemiology, Harvard School of Dental Medicine, Harvard University, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magda","family":"Feres","sequence":"additional","affiliation":[{"name":"Dental Research Division, Department of Periodontology, Guarulhos University, Guarulhos, S\u00e3o Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Applied Oral Science, Forsyth Institute, Cambridge, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynn","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Applied Oral Science, Forsyth Institute, Cambridge, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo","family":"Teles","sequence":"additional","affiliation":[{"name":"Department of Periodontology, University of North Carolina School of Dentistry, Chapel Hill, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1177\/0022034512457373"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0757.2002.290111.x"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1177\/003335491212700505","article-title":"Examining periodontal disease disparities among U.S. adults 20 years of age and older: NHANES III (1988\u20131994) and NHANES 1999\u20132004","volume":"127","author":"Borrell LN","year":"2012","unstructured":"Borrell LN, Talih M. 2012. Examining periodontal disease disparities among U.S. adults 20 years of age and older: NHANES III (1988\u20131994) and NHANES 1999\u20132004. Public Health Rep 127:497\u2013506.","journal-title":"Public Health Rep"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0757.2002.280102.x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-051x.2001.028004296.x"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-051X.2002.290410.x"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.2004.00605.x"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.2008.01304.x"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.2006.01040.x"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.2008.01263.x"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2009.080540"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.2011.01763.x"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.12004"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.12217"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.12026"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1177\/08959374970110010201"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1177\/00220345010800011201"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-9-280"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.2010.01341.x"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.4317\/medoral.18376"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/jre.12110"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.35.5.961"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/34.6.1047"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2014.03.007"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.37.6.1771-1776.1999"},{"key":"e_1_3_2_27_2","first-page":"788","article-title":"Checkerboard DNA-DNA hybridization","volume":"17","author":"Socransky SS","year":"1994","unstructured":"Socransky SS, Smith C, Martin L, Paster BJ, Dwehirst FE, Levin AE. 1994. Checkerboard DNA-DNA hybridization. Biotechniques 17:788\u2013792.","journal-title":"Biotechniques"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-302x.2004.00168.x"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.12117"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2008.070424"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.1982.tb02107.x"},{"key":"e_1_3_2_32_2","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing","volume":"57","author":"Benjamini Y","year":"1995","unstructured":"Benjamini Y, Hochberg Y. 1995. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Series B Stat Methodol 57:289\u2013300.","journal-title":"J R Stat Soc Series B Stat Methodol"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.183.12.3770-3783.2001"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/ismej.2011.191"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0757.2005.00107.x"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/aem.59.11.3850-3857.1993"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12275-010-0299-z"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.b.32755"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.2012.01506.x"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1111\/jam.12316"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.1997.tb01193.x"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.2005.00653.x"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2011.110012"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-302x.2004.00159.x"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.2006.00957.x"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.1998.tb02419.x"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.04974-14","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.04974-14","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T15:23:35Z","timestamp":1717773815000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.04974-14"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,5]]},"references-count":45,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2015,5]]}},"alternative-id":["10.1128\/AAC.04974-14"],"URL":"https:\/\/doi.org\/10.1128\/aac.04974-14","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,5]]},"assertion":[{"value":"2014-12-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-02-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-04-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}