amphotericin-b and Conjunctival-Diseases

Topics: Adult; Amphotericin B; Animals; Antiprotozoal Agents; Conjunctival Diseases; DNA, Protozoan; Eye Infections, Parasitic; Humans; Leishmania tropica; Leishmaniasis, Cutaneous; Male

We report the first case of invasive ophthalmologic infection by Acrophialophora sp. that was successfully treated using voriconazole (VRCZ). Acrophialophora spp., which has been reported to be an opportunistic pathogen, is a rare thermotolerant soil fungus, but its pathogenicity remains unclear. A 77-year-old man had neutropenia and prostate carcinoma and was receiving hemodialysis. His right eye had been infected for 2 days. His conjunctiva was congested, and it partially formed an abscess. Liposomal amphotericin B (L-AMB) was administered following systemic itraconazole. However, the treatment was changed from L-AMB to systemic VRCZ and VRCZ eye drops because his eye symptoms worsened. Subsequently, his symptoms stabilized and his vision was maintained. Acrophialophora sp. was identified by analyzing regions of internal transcribed spacer and domain 1 and 2 of the ribosomal RNA gene. He completed the 7-week systemic VRCZ course. The mean minimum inhibitory concentration of VRCZ for Acrophialophora spp. has been reported to be the lowest among various antifungal agents, and our results indicated the efficacy of VRCZ treatment for Acrophialophora sp. infection. Our results suggest that invasive Acrophialophora sp. infection may require long-term therapy. Further analysis of the clinical spectrum of Acrophialophora spp. infection and adequate treatment methods are required in the future.

Topics: Adolescent; Adult; Aged; Amphotericin B; Antifungal Agents; Ascomycota; Child; Child, Preschool; Cluster Analysis; Conjunctival Diseases; DNA, Fungal; DNA, Ribosomal Spacer; Eye Infections, Fungal; Female; Humans; Immunocompromised Host; Itraconazole; Male; Microbial Sensitivity Tests; Middle Aged; Phylogeny; RNA, Ribosomal; Sequence Analysis, DNA; Treatment Outcome; Ulcer; Uveitis; Voriconazole

The toxicity of conventional formulations of amphotericin B deoxycholate (AmB(DOC)) limits its clinical applications. To reduce the toxicity of AmB(DOC), lipid formulations of amphotericin B (AmB) have been developed and clinically applied. In the present study, we evaluated the ocular toxicity and pharmacokinetics of subconjunctival injection of liposomal AmB.. Subconjunctival injection of either AmB(DOC) (containing 1.5 mg of AmB and 1.2 mg of deoxycholate), deoxycholate (1.2 mg), or liposomal amphotericin B (L-AmB) (containing 1.5 mg of AmB and lipids) was given to white New Zealand rabbits. After 24 hours, toxicities of the drugs were evaluated by slit lamp and histologically. To evaluate the pharmacokinetics of subconjunctival injection of L-AmB, the concentration of the drug in the cornea was evaluated at 4, 12, 24, and 48 hours after subconjunctival injection of L-AmB, with or without corneal epithelial removal.. Subconjunctival injection of AmB(DOC) or deoxycholate alone induced severe corneal and conjunctival edema, with necrosis and infiltration of inflammatory cells. In contrast, subconjunctival injection of L-AmB induced only mild inflammation near the injection site. The concentration of AmB injected in eyes with intact corneal epithelium was 4.93-2.49, 0.63-0.31, 0.15-0.07 microg/g at 4, 12, and 24 hours respectively after the injection of L-AmB. When injected in eyes after corneal epithelial removal, the concentration of AmB was 19.7-9.87, 2.49-1.25, and 1.25-0.63 microg/g at 4, 12, and 24 hours after injection respectively. Subconjunctival injection of L-AmB has reduced ocular toxicities and gives satisfactory concentrations in corneal stroma compared with conventional AmB(DOC). Subconjunctival injection of L-AmB will be a choice of treatment for mycotic keratitis.

Topics: Amphotericin B; Animals; Antifungal Agents; Biological Availability; Conjunctiva; Conjunctival Diseases; Corneal Diseases; Corneal Stroma; Injections; Male; Rabbits