{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T05:21:05Z","timestamp":1780377665473,"version":"3.54.1"},"reference-count":92,"publisher":"Microbiology Society","issue":"5","license":[{"start":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T00:00:00Z","timestamp":1715558400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Research Council","award":["MR\/S004688\/1"],"award-info":[{"award-number":["MR\/S004688\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,13]]},"abstract":"<jats:p>\n                  <jats:bold>Introduction<\/jats:bold>. Bacterial keratitis, particularly caused by <jats:italic>Pseudomonas aeruginosa<\/jats:italic>, is challenging to treat because of multi-drug tolerance, often associated with the formation of biofilms. Antibiotics in development are typically evaluated against planktonic bacteria in a culture medium, which may not accurately represent the complexity of infections <jats:italic>in vivo<\/jats:italic>.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Hypothesis\/Gap Statement.<\/jats:bold> Developing a reliable, economic <jats:italic>ex vivo<\/jats:italic> keratitis model that replicates some complexity of tissue infections could facilitate a deeper understanding of antibiotic efficacy, thus aiding in the optimization of treatment strategies for bacterial keratitis.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Methodology<\/jats:bold>. Here we investigated the efficacy of three commonly used antibiotics (gentamicin, ciprofloxacin and meropenem) against <jats:italic>Pseudomonas aeruginosa<\/jats:italic> cytotoxic strain PA14 and invasive strain PA01 using an <jats:italic>ex vivo<\/jats:italic> porcine keratitis model.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Results<\/jats:bold>. Both strains of <jats:italic>P. aeruginosa<\/jats:italic> were susceptible to the MIC of the three tested antibiotics. However, significantly higher concentrations were necessary to inhibit bacterial growth in the minimum biofilm eradication concentration (MBEC) assay, with both strains tolerating concentrations greater than 512\u2009mg l<jats:sup>\u22121<\/jats:sup> of meropenem. When MIC and higher concentrations than MBEC (1024\u2009mg l<jats:sup>\u22121<\/jats:sup>) of antibiotics were applied, ciprofloxacin exhibited the highest potency against both <jats:italic>P. aeruginosa<\/jats:italic> strains, followed by meropenem, while gentamicin showed the least potency. Despite this, none of the antibiotic concentrations used effectively cleared the infection, even after 18\u2009h of continuous exposure.<\/jats:p>\n               <jats:p>\n                  <jats:bold>Conclusions.<\/jats:bold> Further exploration of antibiotic concentrations and aligning dosing with clinical studies to validate the model is needed. Nonetheless, our <jats:italic>ex vivo<\/jats:italic> porcine keratitis model could be a valuable tool for assessing antibiotic efficacy.<\/jats:p>","DOI":"10.1099\/mic.0.001459","type":"journal-article","created":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T15:17:35Z","timestamp":1715613455000},"source":"Crossref","is-referenced-by-count":12,"title":["Increased tolerance to commonly used antibiotics in a Pseudomonas aeruginosa ex vivo porcine keratitis model"],"prefix":"10.1099","volume":"170","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6460-1468","authenticated-orcid":false,"given":"Katarzyna","family":"Okurowska","sequence":"first","affiliation":[{"name":"National Institute for Health and Care Research, University of Leeds, Leeds LS2 9JT, UK"},{"name":"Department of Chemical and Biological Engineering, University of Sheffield, Sheffield S10 2TN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4637-3059","authenticated-orcid":false,"given":"Peter N.","family":"Monk","sequence":"additional","affiliation":[{"name":"Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield S10 2TN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Karunakaran","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biological Engineering, University of Sheffield, Sheffield S10 2TN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"345","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00203-19"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1038\/s41433-020-01333-9"},{"key":"R3","first-page":"214","article-title":"Corneal blindness: a global perspective","volume":"79","author":"Whitcher","year":"2001","journal-title":"Bull World Health Organ"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1016\/j.survophthal.2018.12.003"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-6420(99)00717-4"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.126.11.1572"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1186\/s12348-023-00363-0"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1038\/eye.2000.2"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2023.1109"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21228671"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1038\/s41433-023-02404-3"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1016\/j.clae.2023.101819"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajic.2009.02.003"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1038\/sj.eye.6700635"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1111\/j.1444-0938.2010.00536.x"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.11-8478"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2008.151167"},{"key":"R18","first-page":"67","article-title":"Microbial keratitis: aetiological diagnosis and clinical features in patients admitted to hospital universiti Sains Malaysia","volume":"49","author":"Norina","year":"2008","journal-title":"Singapore Med J"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1097\/00003226-200405000-00009"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1136\/bmjophth-2017-000086"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2021.101031"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.4103\/0301-4738.40360"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens10020165"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1136\/bmjophth-2022-001002"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1008"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00013-14"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1093\/femsre\/fux010"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003526"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.00913"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001264"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1128\/jb.00568-21"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.02742-22"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.3390\/cells9112450"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.3791\/61156"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2011.06.004"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1076\/ceyr.27.5.289.17220"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1231792100"},{"key":"R38","doi-asserted-by":"publisher","DOI":"10.1093\/gbe\/evy259"},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.001110"},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2013.778"},{"key":"R41","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2004.08.020"},{"key":"R42","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkx288"},{"key":"R43","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00265-21"},{"key":"R44","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0029113"},{"key":"R45","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.02603"},{"key":"R46","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2017.01614"},{"key":"R47","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-0691.2003.00790.x"},{"key":"R48","first-page":"1","article-title":"European society of clinical microbiology and infectious diseases (ESCMID) - European Committee for antimicrobial susceptibility testing (EUCAST) - determination of minimum inhibitory concentration (MIC) by Agar dilution","volume":"6","author":"Hasselmann","year":"2000","journal-title":"Clin Microbiol Infect"},{"key":"R49","year":"2022"},{"key":"R50","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2010.71"},{"key":"R51","doi-asserted-by":"publisher","DOI":"10.1016\/j.mimet.2009.07.017"},{"key":"R52","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.4.1175-1187.2004"},{"key":"R53","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00650-12"},{"key":"R54","doi-asserted-by":"publisher","DOI":"10.1038\/nature02122"},{"key":"R55","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0061625"},{"key":"R56","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-147-1-3"},{"key":"R57","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.15-17077"},{"key":"R58","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01901-13"},{"key":"R59","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05451-11"},{"key":"R60","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01581-12"},{"key":"R61","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2012.04.006"},{"key":"R62","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkq143"},{"key":"R63","doi-asserted-by":"publisher","DOI":"10.5812\/jjm.14358"},{"key":"R64","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2015.07.014"},{"key":"R65","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2010.00213.x"},{"key":"R66","doi-asserted-by":"publisher","DOI":"10.1128\/JB.06112-11"},{"key":"R67","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00854-10"},{"key":"R68","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024008"},{"key":"R69","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2014.00258"},{"key":"R70","doi-asserted-by":"publisher","DOI":"10.1007\/BF00183436"},{"key":"R71","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0b013e318268d6f4"},{"key":"R72","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.4332"},{"key":"R73","doi-asserted-by":"publisher","DOI":"10.1089\/jop.1993.9.271"},{"key":"R74","doi-asserted-by":"publisher","DOI":"10.1016\/s0002-9394(03)00636-6"},{"key":"R75","doi-asserted-by":"publisher","DOI":"10.1016\/s0161-6420(13)31672-8"},{"key":"R76","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/33.5.937"},{"key":"R77","doi-asserted-by":"publisher","DOI":"10.1128\/iai.63.10.4072-4077.1995"},{"key":"R78","doi-asserted-by":"publisher","DOI":"10.1097\/ICL.0000000000000745"},{"key":"R79","doi-asserted-by":"publisher","DOI":"10.4103\/2320-3897.122637"},{"key":"R80","doi-asserted-by":"publisher","DOI":"10.1016\/s0924-8579(02)00192-9"},{"key":"R81","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00689-07"},{"key":"R82","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02584-13"},{"key":"R83","doi-asserted-by":"publisher","DOI":"10.1097\/00006982-199903000-00007"},{"key":"R84","doi-asserted-by":"publisher","DOI":"10.1590\/1414-431X20175901"},{"key":"R85","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.08-3201"},{"key":"R86","doi-asserted-by":"publisher","DOI":"10.1089\/jop.2006.81"},{"key":"R87","doi-asserted-by":"publisher","DOI":"10.1007\/s12009-001-0055-4"},{"key":"R88","first-page":"301","article-title":"Efficacy of topical ciprofloxacin 0.3% in the treatment of ulcerative keratitis in humans","volume":"30","author":"Levey","year":"1998","journal-title":"Ann Ophthalmol Glaucoma"},{"key":"R89","doi-asserted-by":"publisher","DOI":"10.3791\/58562"},{"key":"R90","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10163486"},{"key":"R91","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.663212"},{"key":"R92","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.7.3866-3874.2003"}],"container-title":["Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/micro\/10.1099\/mic.0.001459?crawler=true&mimetype=application\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T15:17:43Z","timestamp":1715613463000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.microbiologyresearch.org\/content\/journal\/micro\/10.1099\/mic.0.001459"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,13]]},"references-count":92,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5,13]]}},"URL":"https:\/\/doi.org\/10.1099\/mic.0.001459","relation":{},"ISSN":["1350-0872","1465-2080"],"issn-type":[{"value":"1350-0872","type":"print"},{"value":"1465-2080","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,13]]}}}