{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:56:57Z","timestamp":1787029017442,"version":"build-2736575974"},"reference-count":51,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T00:00:00Z","timestamp":1628553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["LP130100736"],"award-info":[{"award-number":["LP130100736"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>One approach to combat the increasing incidence of multidrug-resistant (MDR) bacterial pathogens involves repurposing existing compounds with known safety and development pathways as new antibacterial classes with potentially novel mechanisms of action. Here, triclabendazole (TCBZ), a drug originally developed to treat Fasciola hepatica (liver fluke) in sheep and cattle, and later in humans, was evaluated as an antibacterial alone or in combination with sub-inhibitory concentrations of polymyxin B (PMB) against clinical isolates and reference strains of key Gram-positive and Gram-negative bacteria. We show for the first time that in vitro, TCBZ selectively kills methicillin-sensitive and methicillin-resistant Staphylococcus aureus and Staphylococcus pseudintermedius at a minimum inhibitory concentration (MIC) range of 2\u20134 \u00b5g\/mL, and vancomycin-resistant enterococci at a MIC range of 4\u20138 \u00b5g\/mL. TCBZ also inhibited key Gram-negative bacteria in the presence of sub-inhibitory concentrations of PMB, returning MIC90 values of 1 \u00b5g\/mL for Escherichia coli, 8 \u00b5g\/mL for Klebsiella pneumoniae, 2 \u00b5g\/mL for Acinetobacter baumannii and 4 \u00b5g\/mL for Pseudomonasaeruginosa. Interestingly, TCBZ was found to be bacteriostatic against intracellular S. aureus but bactericidal against intracellular S. pseudintermedius. Additionally, TCBZ\u2019s favourable pharmacokinetic (PK) and pharmacodynamic (PD) profile was further explored by in vivo safety and efficacy studies using a bioluminescent mouse model of S. aureus sepsis. We show that repeated four-hourly oral treatment of mice with 50 mg\/kg TCBZ after systemic S. aureus challenge resulted in a significant reduction in S. aureus populations in the blood to 18 h post-infection (compared to untreated mice) but did not clear the bacterial infection from the bloodstream, consistent with in vivo bacteriostatic activity. These results indicate that additional pharmaceutical development of TCBZ may enhance its PK\/PD, allowing it to be an appropriate candidate for the treatment of serious MDR bacterial pathogens.<\/jats:p>","DOI":"10.3390\/microorganisms9081697","type":"journal-article","created":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T08:57:14Z","timestamp":1628585834000},"page":"1697","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Repurposing of the Fasciolicide Triclabendazole to Treat Infections Caused by Staphylococcus spp. and Vancomycin-Resistant Enterococci"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5758-6044","authenticated-orcid":false,"given":"Hongfei","family":"Pi","sequence":"first","affiliation":[{"name":"Australian Centre for Antimicrobial Resistance Ecology, Roseworthy Campus, School of Animal and Veterinary Sciences, The University of Adelaide, Roseworthy, SA 5371, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9308-5629","authenticated-orcid":false,"given":"Abiodun D.","family":"Ogunniyi","sequence":"additional","affiliation":[{"name":"Australian Centre for Antimicrobial Resistance Ecology, Roseworthy Campus, School of Animal and Veterinary Sciences, The University of Adelaide, Roseworthy, SA 5371, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhumi","family":"Savaliya","sequence":"additional","affiliation":[{"name":"Australian Centre for Antimicrobial Resistance Ecology, Roseworthy Campus, School of Animal and Veterinary Sciences, The University of Adelaide, Roseworthy, SA 5371, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6313-9371","authenticated-orcid":false,"given":"Hang Thi","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Australian Centre for Antimicrobial Resistance Ecology, Roseworthy Campus, School of Animal and Veterinary Sciences, The University of Adelaide, Roseworthy, SA 5371, Australia"},{"name":"Department of Pharmacology, Toxicology, Internal Medicine and Diagnostics, Faculty of Veterinary Medicine, Vietnam National University of Agriculture, Hanoi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5312-2149","authenticated-orcid":false,"given":"Stephen W.","family":"Page","sequence":"additional","affiliation":[{"name":"Luoda Pharma Pty Ltd., Caringbah, NSW 2229, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernest","family":"Lacey","sequence":"additional","affiliation":[{"name":"Microbial Screening Technologies Pty Ltd., Smithfield, NSW 2164, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5569-7755","authenticated-orcid":false,"given":"Henrietta","family":"Venter","sequence":"additional","affiliation":[{"name":"Health and Biomedical Innovation, Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren J.","family":"Trott","sequence":"additional","affiliation":[{"name":"Australian Centre for Antimicrobial Resistance Ecology, Roseworthy Campus, School of Animal and Veterinary Sciences, The University of Adelaide, Roseworthy, SA 5371, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.jhealeco.2016.01.012","article-title":"Innovation in the pharmaceutical industry: New estimates of R&D costs","volume":"47","author":"DiMasi","year":"2016","journal-title":"J. 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