Okurowska, K. orcid.org/0000-0002-6460-1468, Monk, P.N. orcid.org/0000-0003-4637-3059 and Karunakaran, E. orcid.org/0000-0003-1913-4319 (2024) Increased tolerance to commonly used antibiotics in a Pseudomonas aeruginosa ex vivo porcine keratitis model. Microbiology, 170 (5). 001459. ISSN 1350-0872
Abstract
Introduction. Bacterial keratitis, particularly caused by Pseudomonas aeruginosa, 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 in vivo.
Hypothesis/Gap Statement. Developing a reliable, economic ex vivo 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.
Methodology. Here we investigated the efficacy of three commonly used antibiotics (gentamicin, ciprofloxacin and meropenem) against Pseudomonas aeruginosa cytotoxic strain PA14 and invasive strain PA01 using an ex vivo porcine keratitis model.
Results. Both strains of P. aeruginosa 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 mg l−1 of meropenem. When MIC and higher concentrations than MBEC (1024 mg l−1) of antibiotics were applied, ciprofloxacin exhibited the highest potency against both P. aeruginosa 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 h of continuous exposure.
Conclusions. Further exploration of antibiotic concentrations and aligning dosing with clinical studies to validate the model is needed. Nonetheless, our ex vivo porcine keratitis model could be a valuable tool for assessing antibiotic efficacy.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024 The Authors. This is an open- access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution. |
Keywords: | Pseudomonas aeruginosa; antibiotic susceptibility; ciprofloxacin; ex vivo keratitis; ex vivo porcine cornea model; gentamicin; meropenem; Animals; Pseudomonas aeruginosa; Anti-Bacterial Agents; Swine; Microbial Sensitivity Tests; Pseudomonas Infections; Biofilms; Keratitis; Ciprofloxacin; Disease Models, Animal; Gentamicins; Meropenem |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Engineering (Sheffield) > Department of Chemical and Biological Engineering (Sheffield) |
Funding Information: | Funder Grant number Medical Research Council MR/S004688/1 SOUTH AFRICAN MEDICAL RESEARCH COUNCIL MR/T029552/1 Medical Research Council MC_PC_MR/T029552/1 ANIMAL FREE RESEARCH UK AFR21-PILOT-134 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 26 Jul 2024 16:34 |
Last Modified: | 28 Jul 2024 01:24 |
Status: | Published |
Publisher: | Microbiology Society |
Refereed: | Yes |
Identification Number: | 10.1099/mic.0.001459 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:215283 |