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Good antimicrobial stewardship is essential to prolong the lifespan of existing antibiotics, and new strategies are required to combat infections in man and animals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Hypothesis\/Objectives<\/jats:title><jats:p>To determine the<jats:italic>in vitro<\/jats:italic>interaction of ionophores (narasin or monensin) with antimicrobial adjuvants (<jats:italic>N<\/jats:italic>\u2010acetylcysteine (<jats:styled-content style=\"fixed-case\">NAC<\/jats:styled-content>), Tris\u2010<jats:styled-content style=\"fixed-case\">EDTA<\/jats:styled-content>or disodium<jats:styled-content style=\"fixed-case\">EDTA<\/jats:styled-content>) against bacterial strains representing pathogens associated with canine otitis externa (<jats:styled-content style=\"fixed-case\">OE<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Animal\/Isolates<\/jats:title><jats:p>American Type Culture Collection (ATCC) strains<jats:italic>Staphylococcus aureus<\/jats:italic>29213,<jats:italic>Pseudomonas aeruginosa<\/jats:italic>27853 and<jats:italic>P.\u00a0aeruginosa<\/jats:italic>biofilm producer<jats:styled-content style=\"fixed-case\">PAO<\/jats:styled-content>1, and a clinical isolate of<jats:italic>Proteus mirabilis<\/jats:italic>from a case of canine<jats:styled-content style=\"fixed-case\">OE<\/jats:styled-content>were tested.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and materials<\/jats:title><jats:p>A 2D microdilution checkerboard method was used, allowing calculation of fractional inhibitory concentration index (<jats:styled-content style=\"fixed-case\">FICI<\/jats:styled-content>), dose reduction index (<jats:styled-content style=\"fixed-case\">DRI<\/jats:styled-content>) and plotting of isobolograms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The combination of narasin with either Tris\u2010<jats:styled-content style=\"fixed-case\">EDTA<\/jats:styled-content>or disodium<jats:styled-content style=\"fixed-case\">EDTA<\/jats:styled-content>produced additive effects (<jats:styled-content style=\"fixed-case\">FICI<\/jats:styled-content>\u00a0=\u00a00.75) against<jats:italic>P.\u00a0aeruginosa<\/jats:italic><jats:styled-content style=\"fixed-case\">ATCC<\/jats:styled-content>27853 and<jats:italic>P.\u00a0aeruginosa<\/jats:italic>biofilm producer<jats:styled-content style=\"fixed-case\">ATCC PAO<\/jats:styled-content>1. An additive effect (<jats:styled-content style=\"fixed-case\">FICI<\/jats:styled-content>\u00a0=\u00a00.53\u20130.75) was found against<jats:italic>S.\u00a0aureus<\/jats:italic><jats:styled-content style=\"fixed-case\">ATCC<\/jats:styled-content>29213 when narasin or monensin were combined with<jats:styled-content style=\"fixed-case\">NAC<\/jats:styled-content>. The highest<jats:styled-content style=\"fixed-case\">DRI<\/jats:styled-content>(32\u2010fold) was found with monensin\/<jats:styled-content style=\"fixed-case\">NAC<\/jats:styled-content>where the<jats:styled-content style=\"fixed-case\">MIC<\/jats:styled-content>of monensin\u00a0was reduced from 4 to 0.125\u00a0\u03bcg\/mL.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and clinical importance<\/jats:title><jats:p>The combination of narasin with Tris\u2010<jats:styled-content style=\"fixed-case\">EDTA<\/jats:styled-content>or disodium<jats:styled-content style=\"fixed-case\">EDTA<\/jats:styled-content>is a promising strategy to inhibit the intrinsic resistance elements of Gram\u2010negative bacteria. These novel combinations potentially could be useful as a multimodal approach to treat mixed infections in canine<jats:styled-content style=\"fixed-case\">OE<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/vde.12803","type":"journal-article","created":{"date-parts":[[2019,11,11]],"date-time":"2019-11-11T10:45:19Z","timestamp":1573469119000},"page":"138","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["<i>In vitro<\/i>antimicrobial activity of narasin and monensin in combination with adjuvants against pathogens associated with canine otitis externa"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9415-9893","authenticated-orcid":false,"given":"Wei Yee","family":"Chan","sequence":"first","affiliation":[{"name":"Australian Centre for Antimicrobial Resistance Ecology School of Animal and Veterinary Sciences The University of Adelaide Roseworthy Campus, Mudla Wirra Rd Roseworthy South Australia 5371 Australia"},{"name":"Faculty of Veterinary Medicine Universiti Putra Malaysia 43400 UPM Serdang Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth E.","family":"Hickey","sequence":"additional","affiliation":[{"name":"Australian Centre for Antimicrobial Resistance Ecology School of Animal and Veterinary Sciences The University of Adelaide Roseworthy Campus, Mudla Wirra Rd Roseworthy South Australia 5371 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manouchehr","family":"Khazandi","sequence":"additional","affiliation":[{"name":"Australian Centre for Antimicrobial Resistance Ecology School of Animal and Veterinary Sciences The University of Adelaide Roseworthy Campus, Mudla Wirra Rd Roseworthy South Australia 5371 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5312-2149","authenticated-orcid":false,"given":"Stephen W.","family":"Page","sequence":"additional","affiliation":[{"name":"Luoda Pharma Pty Ltd. 1\/304\u2010318, The Kingsway Caringbah New South Wales 2229 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darren J.","family":"Trott","sequence":"additional","affiliation":[{"name":"Australian Centre for Antimicrobial Resistance Ecology School of Animal and Veterinary Sciences The University of Adelaide Roseworthy Campus, Mudla Wirra Rd Roseworthy South Australia 5371 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7449-4897","authenticated-orcid":false,"given":"Peter B.","family":"Hill","sequence":"additional","affiliation":[{"name":"Australian Centre for Antimicrobial Resistance Ecology School of Animal and Veterinary Sciences The University of Adelaide Roseworthy Campus, Mudla Wirra Rd Roseworthy South Australia 5371 Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,11,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0090501"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/vr.158.16.533"},{"key":"e_1_2_6_4_1","doi-asserted-by":"crossref","first-page":"1,336","DOI":"10.2460\/javma.1999.214.09.1336","article-title":"Health status and population characteristics of dogs and cats examined at private veterinary practices in the United States","volume":"214","author":"Lund EM","year":"1999","journal-title":"J Am Vet Med Assoc"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0176379"},{"key":"e_1_2_6_6_1","first-page":"98","article-title":"Microbiological diagnosis and bacterial multiresistance in vitro of external otitis of dogs\u2010short communication","volume":"21","author":"Moraes L","year":"2014","journal-title":"Vet Zootec"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1590\/S1517-83822011000400027"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/vr.d2393"},{"key":"e_1_2_6_9_1","unstructured":"O'NeillJ.Tackling drug\u2010resistant infections globally: final report and recommendations. 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