April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Corneal Pharmacokinetics of Meropenem
Author Affiliations & Notes
  • Henri Sueke
    Ophthalmology, Royal Liverpool University Hospital, Liverpool, United Kingdom
    Eye and Vision Science, University of Liverpool, Liverpool, United Kingdom
  • Tim Neal
    Ophthalmology, Royal Liverpool University Hospital, Liverpool, United Kingdom
  • Stephen J Tuft
    Ophthalmology, Moorfields Hospital, London, United Kingdom
  • Mark Wilkinson
    Eye and Vision Science, University of Liverpool, Liverpool, United Kingdom
  • Yalin Zheng
    Eye and Vision Science, University of Liverpool, Liverpool, United Kingdom
  • Craig Winstanley
    Eye and Vision Science, University of Liverpool, Liverpool, United Kingdom
  • Stephen Kaye
    Ophthalmology, Royal Liverpool University Hospital, Liverpool, United Kingdom
    Eye and Vision Science, University of Liverpool, Liverpool, United Kingdom
  • Footnotes
    Commercial Relationships Henri Sueke, None; Tim Neal, None; Stephen Tuft, None; Mark Wilkinson, None; Yalin Zheng, None; Craig Winstanley, None; Stephen Kaye, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 5789. doi:
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    • Get Citation

      Henri Sueke, Tim Neal, Stephen J Tuft, Mark Wilkinson, Yalin Zheng, Craig Winstanley, Stephen Kaye; Corneal Pharmacokinetics of Meropenem. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5789.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract
 
Purpose
 

To evaluate the corneal pharmacokinetics of meropenem, a potentially novel antimicrobial in treating bacterial keratitis we quantify (1) the toxicity of meropenem compared to moxifloxacin on corneal cells in culture (2) the corneal penetration of meropenem across corneas mounted on artificial anterior chambers.

 
Methods
 

Human keratocyte cells (HKCs) and human corneal epithelial cells (HCE-Ts) in culture, were treated with either 5mg/ml or 2.5 mg/ml of meropenem or moxifloxacin for 1 hour. MTT cell viability assay was used to compare cell toxicity. Absorbance was read using an automated microplate reader and cell viability was expressed as percentages in relation to controls. Cell morphology of HKCs and HCE-Ts were assessed with fluorescent microscopy after incubation with meropenem compared to controls. Human cadaver corneas were used in corneal penetration experiments. Epithelium and endothelium were removed mechanically and corneas were mounted onto artificial anterior chambers. 10mg/ml of meropenem was inserted onto the corneas and samples of fluid in the artificial anterior chamber were removed at 45minutes, 1.5hrs, 3.5hrs and 24hrs. Meropenem concentrations were estimated from corneal homogenate and anterior chamber samples using; (1) disc diffusion bioassay measuring zones of inhibition when samples incubated with Escherichia Coli on agar plates and (2) reverse-phase High-Performance Liquid Chromatography (HPLC).

 
Results
 

MTT assays of HCE-T and HKC cells showed meropenem had significantly higher cell viability at both 5mg/ml and 2.5mg/ml compared to moxifloxacin p<0.05. Cell morphology of meropenem was indistinguishable from controls. Graph 1 summarises the diffusion of meropenem across 18 corneas. The mean corneal penetration of meropenem even at the earliest sampling point (45 minutes) were 4 times higher than the MIC90 seen with meropenem against keratitis isolates in a previous study. Concentrations of meropenem were seen to increase steadily throughout the sampling time period. Meropenem concentrations measured with bioassay were much higher than HPLC measurements.

 
Conclusions
 

We have previously shown meropenem to have excellent in vitro activity against both Gram positive and Gram negative isolates from patients with bacterial keratitis. This study suggests a good safety profile against corneal cells in culture. High corneal penetration of meropenem was seen at the earliest sampling point well in excess of the MIC90.

  
Keywords: 573 keratitis • 422 antibiotics/antifungals/antiparasitics • 480 cornea: basic science  
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