{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:57:33Z","timestamp":1777597053429,"version":"3.51.4"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T00:00:00Z","timestamp":1697587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T00:00:00Z","timestamp":1697587200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Department of Education and Training | Australian Research Council","award":["LP110200770"],"award-info":[{"award-number":["LP110200770"]}]},{"name":"Department of Education and Training | Australian Research Council","award":["LP110200770"],"award-info":[{"award-number":["LP110200770"]}]},{"name":"Department of Education and Training | Australian Research Council","award":["LP110200770"],"award-info":[{"award-number":["LP110200770"]}]},{"DOI":"10.13039\/501100001787","name":"University of South Australia","doi-asserted-by":"crossref","award":["Research Fund"],"award-info":[{"award-number":["Research Fund"]}],"id":[{"id":"10.13039\/501100001787","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2023,10,18]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            We have previously reported promising\n            <jats:italic>in vivo<\/jats:italic>\n            activity of the first-generation 2-aminopyramidine robenidine analogue NCL195 against Gram-positive bacteria (GPB) when administered via the systemic route. In this study, we examined the efficacy of oral treatment with NCL195 (\u00b1 low-dose colistin) in comparison to oral moxifloxacin in bioluminescent\n            <jats:italic>Staphylococcus aureus<\/jats:italic>\n            and\n            <jats:italic>Escherichia coli<\/jats:italic>\n            peritonitis-sepsis models. Four oral doses of 50 mg\/kg NCL195, commencing immediately post-infection, were administered at 4 h intervals in the\n            <jats:italic>S. aureus<\/jats:italic>\n            peritonitis-sepsis model. We used a combination of four oral doses of 50 mg\/kg NCL195 and four intraperitoneal doses of colistin at 0.125 mg\/kg, 0.25 mg\/kg, or 0.5 mg\/kg in the\n            <jats:italic>E. coli<\/jats:italic>\n            peritonitis-sepsis model. Subsequently, the dose rates of four intraperitoneal doses of colistin were increased to 0.5 mg\/kg, 1 mg\/kg, or 2 mg\/kg at 4 h intervals to treat a colistin-resistant\n            <jats:italic>E. coli<\/jats:italic>\n            infection. In the\n            <jats:italic>S. aureus<\/jats:italic>\n            infection model, oral treatment of mice with NCL195 resulted in significantly reduced\n            <jats:italic>S. aureus<\/jats:italic>\n            infection loads (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.01) and longer survival times (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.001) than vehicle-only treated mice. In the\n            <jats:italic>E. coli<\/jats:italic>\n            infection model, co-administration of NCL195 and graded doses of colistin resulted in a dose-dependent significant reduction in colistin-susceptible (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.01) or colistin-resistant (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.05)\n            <jats:italic>E. coli<\/jats:italic>\n            loads compared to treatment with colistin alone at similar concentrations. Our results confirm that NCL195 is a potential candidate for further preclinical development as a specific treatment for multidrug-resistant infections, either as a stand-alone antibiotic for GPB or in combination with sub-inhibitory concentrations of colistin for Gram-negative bacteria.\n          <\/jats:p>","DOI":"10.1128\/aac.00424-23","type":"journal-article","created":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T14:33:28Z","timestamp":1694442808000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Oral administration of a 2-aminopyrimidine robenidine analogue (NCL195) significantly reduces\n            <i>Staphylococcus aureus<\/i>\n            infection and reduces\n            <i>Escherichia coli<\/i>\n            infection in combination with sub-inhibitory colistin concentrations in a bioluminescent mouse model"],"prefix":"10.1128","volume":"67","author":[{"given":"Hang Thi","family":"Nguyen","sequence":"first","affiliation":[{"name":"Australian Center for Antimicrobial Resistance Ecology, School of Animal and Veterinary Sciences, The University of Adelaide , Adelaide, South Australia, Australia"},{"name":"Department of Pharmacology, Toxicology, Internal Medicine and Diagnostics, Faculty of Veterinary Medicine, Vietnam National University of Agriculture , Hanoi, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henrietta","family":"Venter","sequence":"additional","affiliation":[{"name":"Health and Biomedical Innovation, Clinical and Health Sciences, University of South Australia , Adelaide, South Australia, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucy","family":"Woolford","sequence":"additional","affiliation":[{"name":"School of Animal and Veterinary Sciences, The University of Adelaide , Adelaide, South Australia, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly A.","family":"Young","sequence":"additional","affiliation":[{"name":"Chemistry, School of Environmental and Life Sciences, University of Newcastle , Callaghan, New South Wales, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"McCluskey","sequence":"additional","affiliation":[{"name":"Chemistry, School of Environmental and Life Sciences, University of Newcastle , Callaghan, New South Wales, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjay","family":"Garg","sequence":"additional","affiliation":[{"name":"Clinical and Health Sciences, University of South Australia , Adelaide, South Australia, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvia S.","family":"Sapula","sequence":"additional","affiliation":[{"name":"Health and Biomedical Innovation, Clinical and Health Sciences, University of South Australia , Adelaide, South Australia, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen W.","family":"Page","sequence":"additional","affiliation":[{"name":"Neoculi Pty Ltd. , Burwood, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abiodun David","family":"Ogunniyi","sequence":"additional","affiliation":[{"name":"Australian Center for Antimicrobial Resistance Ecology, School of Animal and Veterinary Sciences, The University of Adelaide , Adelaide, South Australia, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8297-5770","authenticated-orcid":false,"given":"Darren J.","family":"Trott","sequence":"additional","affiliation":[{"name":"Australian Center for Antimicrobial Resistance Ecology, School of Animal and Veterinary Sciences, The University of Adelaide , Adelaide, South Australia, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1080\/14787210.2020.1813022"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00181-19"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)02724-0"},{"key":"e_1_3_4_5_2","first-page":"1","volume-title":"Tackling drug-resistant infections globally: final report and recommendations","author":"O\u2019Neill J","year":"2016","unstructured":"O\u2019Neill J . 2016. Tackling drug-resistant infections globally: final report and recommendations, p 1\u201380. Wellcome Trust and UK Government, London."},{"key":"e_1_3_4_6_2","unstructured":"World Health Organization\n. 2019. New report calls for urgent action to avert antimicrobial resistance crisis. Available from: https:\/\/www.who.int\/news\/item\/29-04-2019-new-report-calls-for-urgent-action-to-avert-antimicrobial-resistance-crisis"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00920-19"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(17)30753-3"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw829"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2017.10.028"},{"key":"e_1_3_4_11_2","unstructured":"Pewtrusts\n. 2021. Tracking the global pipeline of antibiotics in development. 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