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Evaluation of the in vitro activity of commercially available moxifloxacin and voriconazole eye-drops against clinical strains of Acanthamoeba

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Abstract

Purpose

Acanthamoeba is an opportunistic pathogen which is the causal agent of a sight-threatening ulceration of the cornea known as “Acanthamoeba keratitis” (AK) and, more rarely, an infection of the central nervous system called “granulomatous amoebic encephalitis” (GAE). The symptoms of AK are non-specific, and so it can be misdiagnosed as a viral, bacterial, or fungal keratitis. Furthermore, current therapeutic measures against AK are arduous, and show limited efficacy against the cyst stage of Acanthamoeba. Moxifloxacin, a fourth generation fluoroquinolone, has been used with other drugs to treat GAE, but its efficacy as a treatment for AK is not known. Voriconazole has been used to treat AK; however, its cysticidal efficacy is not known. Both drugs are commercially available as eye-drops. The aim of this study was to evaluate the in-vitro activity of these eye-drops against Acanthamoeba compared to two reference drugs (chlorhexidine and amphotericin B) which are currently used to treat AK and GAE.

Methods

The sensitivity of two clinical and one type strain of Acanthamoeba to the commercial concentrations of the four drugs was evaluated with a colorimetric assay. Mature cysts were incubated with voriconazole to determine their sensitivity to this drug. The effects on cell proliferation and cell toxicity were determined using standard procedures with commercial kits.

Results

The four compounds were active against the Acanthamoeba strains in this study. Although it prevented encystation, moxifloxacin’s amoebicidal activity was low. Voriconazole activity was greater than that of the other drugs, even at a concentration lower than in commercial eye drops. It was effective against cysts and decreased cell proliferation, with low cellular cytotoxicity.

Conclusion

Voriconazole could be used against AK as a first-line treatment or in combination. Moxifloxacin is an interesting adjuvant to consider as it is effectively prevents encystation of the amoeba which often complicates infection resolution. In addition, moxifloxacin is effective in preventing secondary bacterial infections.

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Acknowledgement

The authors are grateful to Dr. Sutherland K. Maciver for his critical editing and revision of the manuscript.

Financial support

This work was supported by the grants RICET (project no. RD06/0021/0005 of the programme of Redes Temáticas de Investigación Cooperativa, FIS), Spanish Ministry of Health, Madrid, Spain and the Project FIS PI10/01298 “Protozoosis emergentes por amebas de vida libre:aislamiento y caracterización molecular, identificación de cepas transportadoras de otros agentes patógenos y búsqueda de quimioterapias efectivas” from the Instituto de Salud Carlos III.

CMMN was supported by a postdoctoral grant from the Fundación Canaria Manuel Morales, La Palma, Canary Islands. JLM was supported by the Ramón y Cajal Subprogramme from the Spanish Ministry of Economy and Competivity RYC-2011-08863. ALA was funded by a grant “Ayudas del Programa de Formación de Personal Investigador, para la realización de Tesis Doctorales” from the Agencia Canaria de Investigación, Innovación y Sociedad de la Información from the Canary Islands Government.

This work was also supported by grants to F.A-M from Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo (PI021056), and Fundación Mutua Madrileña, Spain.

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Authors and Affiliations

  1. University Institute of Tropical Diseases and Public Health of the Canary Islands, University of La Laguna, Avda Astrofísico Fco. Sánchez, S/N, 38203 La Laguna, Tenerife, Canary Islands, Spain

    C. M. Martín-Navarro, A. López-Arencibia, B. Valladares, J. E. Piñero & J. Lorenzo-Morales

  2. Centre for Integrative Physiology, University of Edinburgh, Scotland, UK

    C. M. Martín-Navarro

  3. Cornea Unit, Department of Ophthalmology, Ramón y Cajal Hospital, Madrid, Spain

    F. Arnalich-Montiel

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  1. C. M. Martín-Navarro
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  2. A. López-Arencibia
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  3. F. Arnalich-Montiel
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  4. B. Valladares
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  5. J. E. Piñero
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  6. J. Lorenzo-Morales
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Correspondence to C. M. Martín-Navarro.

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Martín-Navarro, C.M., López-Arencibia, A., Arnalich-Montiel, F. et al. Evaluation of the in vitro activity of commercially available moxifloxacin and voriconazole eye-drops against clinical strains of Acanthamoeba . Graefes Arch Clin Exp Ophthalmol 251, 2111–2117 (2013). https://doi.org/10.1007/s00417-013-2371-y

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