{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T21:45:03Z","timestamp":1774907103064,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007197","name":"U.S. Public Health Service","doi-asserted-by":"publisher","award":["R21 DE018804"],"award-info":[{"award-number":["R21 DE018804"]}],"id":[{"id":"10.13039\/100007197","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> <jats:italic>Aggregatibacter actinomycetemcomitans<\/jats:italic> resists killing by neutrophils and is inhibited by azithromycin (AZM) and amoxicillin (AMX). AZM actively concentrates inside host cells, whereas AMX enters by diffusion. The present study is conducted to determine whether AZM is more effective than AMX at enhancing phagocytic killing of <jats:italic>A. actinomycetemcomitans<\/jats:italic> by neutrophils.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Killing assays were conducted in the presence of either 2 \u03bcg\/mL AZM or 16 \u03bcg\/mL AMX (equipotent against <jats:italic>A. actinomycetemcomitans<\/jats:italic>). Neutrophils were loaded by incubation with the appropriate antibiotic. Opsonized <jats:italic>A. actinomycetemcomitans<\/jats:italic> strain Y4 was incubated with the indicated antibiotic alone, with loaded neutrophils and antibiotic, or with control neutrophils (without antibiotic) at multiplicities of infection (MOIs) of 30 and 90 bacteria per neutrophil.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Neutrophil incubation with 2 \u03bcg\/mL AZM yielded an intracellular concentration of 10 \u03bcg\/mL. At an MOI of 30, neutrophils loaded with AZM failed to kill significantly more bacteria than control neutrophils during the 60\u2010 and 90\u2010minute assay periods. At an MOI of 90, neutrophils loaded with AZM killed significantly more bacteria than either AZM alone or control neutrophils during 60\u2010 and 90\u2010minute incubations (<jats:italic>P<\/jats:italic> &lt;0.05), and killed significantly more bacteria after 90 minutes than the sum of the killing produced by AZM alone or neutrophils alone. Neutrophils incubated with AMX under identical conditions also killed significantly more bacteria than either AMX alone or control neutrophils, but there was no evidence of synergism between AMX and neutrophils.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> Neutrophils possess a concentrative transport system for AZM that may enhance killing of <jats:italic>A. actinomycetemcomitans.<\/jats:italic> Its effects are most pronounced when neutrophils are greatly outnumbered by bacteria.<\/jats:p>","DOI":"10.1902\/jop.2014.140183","type":"journal-article","created":{"date-parts":[[2014,9,4]],"date-time":"2014-09-04T09:30:32Z","timestamp":1409823032000},"page":"155-161","source":"Crossref","is-referenced-by-count":17,"title":["Azithromycin Enhances Phagocytic Killing of <i>Aggregatibacter actinomycetemcomitans<\/i> Y4 by Human Neutrophils"],"prefix":"10.1002","volume":"86","author":[{"given":"Pin\u2010Chuang","family":"Lai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark R.","family":"Schibler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John D.","family":"Walters","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,1]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1902\/annals.1999.4.1.1"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/iai.29.3.1013-1020.1980"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.1982.tb02022.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00653-07"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0757.1999.tb00161.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.1986.57.8.492"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034510363682"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.1987.tb01561.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-302X.1993.tb00655.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.63.12.4589-4594.1995"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.1983.tb02179.x"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.1992.63.1.52"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02558-12"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01975835"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.36.6.1241"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2012.110558"},{"key":"e_1_2_7_18_1","first-page":"77","article-title":"Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g","volume":"97","author":"B\u00f6yum A","year":"1968","journal-title":"Scand J Clin Lab Invest Suppl"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.1985.tb01348.x"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.7.1.15"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.10.2099"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2010.100221"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.11.2801"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/153.3.593"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.21.3.373"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0757.1996.tb00068.x"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkg482"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.idc.2004.04.012"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccc.2007.12.008"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2005.00601.x"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0924-8579(01)00430-7"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.2010.01325.x"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.11.3000"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2011.03.021"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2008.05.007"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.1991.tb00070.x"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.2009.01449.x"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.14.4.727-752.2001"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.1980.tb00304.x"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.2008.01254.x"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2005.76.3.426"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.2010.01607.x"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-302X.2007.00403.x"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdent.2012.03.004"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2007.060247"}],"container-title":["Journal of Periodontology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aap.onlinelibrary.wiley.com\/doi\/pdf\/10.1902\/jop.2014.140183","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T12:12:09Z","timestamp":1760875929000},"score":1,"resource":{"primary":{"URL":"https:\/\/aap.onlinelibrary.wiley.com\/doi\/10.1902\/jop.2014.140183"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,1]]},"references-count":44,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015,1]]}},"alternative-id":["10.1902\/jop.2014.140183"],"URL":"https:\/\/doi.org\/10.1902\/jop.2014.140183","archive":["Portico"],"relation":{},"ISSN":["0022-3492","1943-3670"],"issn-type":[{"value":"0022-3492","type":"print"},{"value":"1943-3670","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,1]]}}}