Penetration of 0.3% ciprofloxacin, 0.3% ofloxacin, and 0.5% moxifloxacin into the cornea and aqueous humor of enucleated human eyes

Silva, G.C.M.; Jabor, Valquíria Aparecida Polisel; Bonato, Pierina Sueli; Martinez, Edson Zangiacomi; Sousa, Sidney Júlio de Faria e

doi:10.1590/1414-431x20175901

Cited by 6 publications

(3 citation statements)

References 22 publications

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“…Ciprofloxacin has a very good tissue penetration property. Exposure to this antibiotic for as short as 10 minutes has been demonstrated to result in concentrations exceeding MIC in human cornea ex vivo (Silva et al, 2017, McDermott et al, 1993, Akkan et al, 1997, Ozturk et al, 1999) therefore we suspect that the 18-hour continuous exposure to this antibiotic in our study very likely resulted in MIC concentration in corneal tissue. Ciprofloxacin was very effective in eradicating P. aeruginosa at higher concentrations in our experiments, which is in line with studies in vivo .…”

Section: Discussionmentioning

confidence: 84%

Increased tolerance to commonly used antibiotics in aPseudomonas aeruginosa ex vivoporcine keratitis model

Okurowska,

Monk,

Karunakaran

2023

Preprint

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Global trends show increase in microbial infections caused by pathogens resistant to the most common antibiotics. Antibiotics in development are usually tested on rapidly dividing cells in a culture medium and do not reflect complexity of infections in vivo, while testing in vivo is limited, expensive and ethically concerning. This often results in development and subsequent prescription of antibiotics only targeting infections in which pathogens are undergoing rapid cell division and in case of persistent infections like keratitis leads to poor clinical outcomes such as impaired vision or loss of an eye. In this study, we demonstrate antibiotic tolerance of Pseudomonas aeruginosa strains PAO1 and PA14 using the ex vivo porcine keratitis model in which bacterial physiology more closely mimics infections in vivo than in a culture medium. MBEC and MIC was used as a guideline to establish concentration of applied antibiotics on tissue. Infected ex vivo porcine corneas were treated with therapeutically relevant concentrations of gentamicin, ciprofloxacin, chloramphenicol, clindamycin and fusidic acid. Ciprofloxacin was the most potent across all tests demonstrating a positive correlation with MIC but not MBEC. Nonetheless, the results demonstrated that MIC and MBEC concentrations were not sufficient to clear infection even after 18 hours of continuous exposure to the tested antibiotics reflecting the need for novel antibiotics that can target the persistent subpopulation of these pathogens and the ability of the ex vivo keratitis model to be a relevant platform to identify novel antibiotics with suitable activities. There was a clear visual distinction between corneas infected with cytotoxic strain PA14 and invasive strain PAO1. In this study both strains PA14 and PAO1 showed a high level of antibiotic tolerance, which suggests that in clinical settings the treatment approach could be similar regardless of the causative strain.

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Section: Discussionmentioning

confidence: 84%

Increased tolerance to commonly used antibiotics in aPseudomonas aeruginosa ex vivoporcine keratitis model

Okurowska,

Monk,

Karunakaran

2023

Preprint

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“…Ciprofloxacin exhibits good tissue and cell penetration properties, with studies demonstrating that even brief exposure of as little as 10 min can lead to concentrations surpassing the MIC in human corneas ex vivo [ 75 83 84 ]. The factors that contribute to ciprofloxacin’s high permeability include the low molecular mass and lipophilicity, allowing crossing through the hydrophobic corneal epithelium [ 85 ].…”

Section: Discussionmentioning

confidence: 99%

Increased tolerance to commonly used antibiotics in a Pseudomonas aeruginosa ex vivo porcine keratitis model

Okurowska,

Monk,

Karunakaran

2024

Microbiology

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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.

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“…Ocular drug delivery devices have demonstrated improved drug uptake over conventional drug formulations. For example, higher uptake was measured through a corneal ring (13 μg/g in the cornea and 4 μg/mL in the aqueous humour) (Shikamura et al, 2016), as compared to a topical solution (6.95 μg/g in the cornea and 1.42 ng/μg in the aqueous humor) (Silva et al, 2017). However, besides on the delivery route, the level of drug uptake can be influenced significantly by a number of factors.…”

Section: Challenges In Pharmacokineticsmentioning

confidence: 99%

Topical drug delivery devices: A review

Bertens

Gijs

Biggelaar

et al. 2018

Experimental Eye Research

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Penetration of 0.3% ciprofloxacin, 0.3% ofloxacin, and 0.5% moxifloxacin into the cornea and aqueous humor of enucleated human eyes

Cited by 6 publications

References 22 publications

Increased tolerance to commonly used antibiotics in aPseudomonas aeruginosa ex vivoporcine keratitis model

Increased tolerance to commonly used antibiotics in aPseudomonas aeruginosa ex vivoporcine keratitis model

Increased tolerance to commonly used antibiotics in a Pseudomonas aeruginosa ex vivo porcine keratitis model

Topical drug delivery devices: A review

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