title: Evaluation of the in vitro activity of commercially available moxifloxacin and voriconazole eye-drops against clinical strains of Acanthamoeba.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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, cmmartin@ull.es.
authors.forename: C M
authors.initials: CM
authors.lastname: Martín-Navarro
authors.forename: A
authors.initials: A
authors.lastname: López-Arencibia
authors.forename: F
authors.initials: F
authors.lastname: Arnalich-Montiel
authors.forename: B
authors.initials: B
authors.lastname: Valladares
authors.forename: J E
authors.initials: JE
authors.lastname: Piñero
authors.forename: J
authors.initials: J
authors.lastname: Lorenzo-Morales
mesh_terms: D048248:Acanthamoeba castellanii / Q000187:drug effects* / Q000254:growth & development; D000563:Amebicides / Q000494:pharmacology; D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D001372:Aza Compounds / Q000494:pharmacology*; D002710:Chlorhexidine / Q000494:pharmacology; D003124:Colorimetry; D004338:Drug Combinations; D024841:Fluoroquinolones; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D000077266:Moxifloxacin; D009883:Ophthalmic Solutions; D021261:Parasitic Sensitivity Tests; D011743:Pyrimidines / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*; D065819:Voriconazole
chemical_list: D000563:Amebicides; D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D001372:Aza Compounds; D004338:Drug Combinations; D024841:Fluoroquinolones; D009883:Ophthalmic Solutions; D011743:Pyrimidines; D011804:Quinolines; D014230:Triazoles; D000666:Amphotericin B; D065819:Voriconazole; D002710:Chlorhexidine; D000077266:Moxifloxacin