amphotericin-b and Acanthamoeba-Keratitis

For the past several decades, there has been little improvement in the morbidity and mortality associated with Acanthamoeba keratitis and Acanthamoeba encephalitis, respectively. The discovery of a plethora of antiacanthamoebic compounds has not yielded effective marketed chemotherapeutics. The rate of development of novel antiacanthamoebic chemotherapies of translational value and the lack of interest of the pharmaceutical industry in developing such chemotherapies have been disappointing. On the other hand, the market for contact lenses/contact lens disinfectants is a multi-billion-dollar industry and has been successful and profitable. A better understanding of drugs, their targets, and mechanisms of action will facilitate the development of more-effective chemotherapies. Here, we review the progress toward phenotypic drug discovery, emphasizing the shortcomings of useable therapies.

Topics: Acanthamoeba; Acanthamoeba Keratitis; Amphotericin B; Animals; Antiprotozoal Agents; Azoles; Biguanides; Caspofungin; Cefazolin; Chlorhexidine; Echinocandins; Humans; Infectious Encephalitis; Lipopeptides; Meropenem; Natamycin; Polymyxin B; Thienamycins

Acanthamoeba spp. are the causative agents of a sight-threatening infection of the cornea known as Acanthamoeba keratitis (AK). Amphotericin B - deoxycholate (AB) is used in the treatment of infectious keratitis, however, its topical administration has side effects as blepharitis, iritis, and painful instillation. In this context, the preheating of AB can decrease its toxicity by the formation of super aggregates (hAB). hAB associated with a thermoreversible in situ gelling ophthalmic system is a promising option due to the latter biocompatibility, low toxicity, and high residence time on the ocular surface. Our objective was to develop a topical ocular formulation of hAB for the treatment of AK. After heating at 70°C for 20 min, hAB was incorporated into a thermoreversible gelling system. The amebicidal activity of AB and hAB was evaluated against trophozoites and cysts of A. castellanii (ATCC 50492) and a regional clinical isolate (IC01). The results showed that the preheating of AB did not change the pharmacological action of the drug, with the amebicidal effect of AB and hAB under trophozoites and cysts of Acanthamoeba spp. The thermoreversible system remained stable, allowing the increase of drug retention time. For assessment of cytotoxicity, HUVEC (ATCC® CRL-1730) cells were challenged with AB and hAB for 48h. Cell viability was assessed, and hAB did not show cytotoxicity for HUVEC cells. As far as we know this was the first study that showed the preheated AB associated with a thermoreversible in situ gelling ophthalmic system as a promising system for topical ocular topical administration of hAB for AK therapy.

Topics: Acanthamoeba; Acanthamoeba Keratitis; Amebicides; Amphotericin B; Animals; Trophozoites

Topics: Acanthamoeba; Acanthamoeba Keratitis; Amphotericin B; Antifungal Agents; Antiprotozoal Agents; Conjunctiva; Cornea; Corneal Ulcer; Drug Therapy, Combination; Eye Infections, Fungal; Fungi; Global Health; Health Care Surveys; Humans; Microscopy, Confocal; Natamycin; Polymerase Chain Reaction; Practice Patterns, Physicians'; Surveys and Questionnaires

The free-living amoeba (FLA) Acanthamoeba sp. is an opportunistic pathogen that can cause amoebic keratitis (AK) or granulomatous amoebic encephalitis (GAE). While current treatments of AK are long with some relapses, no consensus therapy has been developed for GAE remaining lethal in 90% of the cases. In this context, efficient antiacanthamoebal drugs have to be identified. In this work, 15 drugs used in the treatment of AK or GAE or in other parasitic diseases were evaluated for their in vitro activity on A. castellanii. Hexamidine, voriconazole and clotrimazole exhibited the highest activities with IC

Topics: Acanthamoeba castellanii; Acanthamoeba Keratitis; Amebiasis; Amphotericin B; Anti-Infective Agents; Benzamidines; Humans; Inhibitory Concentration 50; Parasitic Sensitivity Tests; Voriconazole

To describe a case of keratomycosis caused by Arthrographis kalrae, mimicking Acanthamoeba keratitis.. Case report.. A 23-year-old female contact lens wearer developed dendritic keratitis in her amblyopic eye (OD). Baseline vision was 20/50. Treatment with trifluridine 1% resulted in resolution of the dendrite, but an area of stromal haze developed, spreading to a discontinuous ring shape, and the vision dropped to 20/200. Photophobia was intense, and pain was out of proportion to the examination. Cultures were sent, and empiric treatment of Acanthamoeba was begun, without subsequent improvement. After 4 weeks, cultures were positive for a fungal species. Amphotericin 0.5% drops were begun, with moderately rapid resolution of the active keratitis. At last follow-up, best-corrected vision was 20/100. Review of the culture showed the organism to be Arthrographis kalrae.. Arthrographis kalrae has been reported only once before as an ocular pathogen. As in the previously reported case of Arthrographis, our patient's presentation was strongly suggestive of Acanthamoeba keratitis.

Topics: Acanthamoeba Keratitis; Adult; Amphotericin B; Antifungal Agents; Diagnosis, Differential; Eye Infections, Fungal; Female; Humans; Keratitis; Keratitis, Dendritic; Mitosporic Fungi; Mycoses; Ophthalmic Solutions