Recalcitrant Fungal Keratitis Research Articles

Successful Medical Management of Recalcitrant Fusarium solani Keratitis: Molecular Identification and Susceptibility Patterns

Fungal keratitis is a rare but sight-threatening infection of the cornea that may be caused by several fungal pathogens. A delay in diagnosis and inadequate treatment may even lead to loss of the affected eye. Fungal keratitis is often misdiagnosed as bacterial keratitis because isolation and identification of the fungal pathogen is difficult and requires experience, and fungal growth in culture requires time. In this report, a 14-year-old boy with recalcitrant Fusarium solani keratitis, unresponsive to initial therapy, is presented. CLSI M38-A2 in vitro antifungal susceptibility tests demonstrated that only amphotericin B (0.5 μg/ml) had potent activity against F. solani; however, fluconazole (>64 μg/ml), itraconazole (>16 μg/ml), voriconazole (8 μg/ml), and posaconazole (>16 μg/ml) had high minimum inhibitory concentrations. In addition, caspofungin (>16 μg/ml) and anidulafungin (>16 μg/ml) exhibited high minimum effective concentrations. Repeated intrastromal voriconazole injections, topical voriconazole, and caspofungin combined with systemic antifungal agents improved of the corneal lesion with a significant increase in visual acuity. Intrastromal voriconazole injection may be used as an adjunctive treatment method for recalcitrant fungal keratitis with no prominent complications. The intrastromal route could be an effective route of administration of antifungal agents, especially for F. solani keratitis, as in this case. A combination of various antifungal agents administered by different routes prevented loss of the eye.

Pharmacokinetics comparison of amphotericin B using three administrating approach in a rabbit model

Background Intracameral or intracorneal administration of amphotericin B (AMB) can achieve significant therapeutic efficacy in the treatment of recalcitrant fungal keratitis in cases that do not respond to conventional antifungal therapy. However, the ocular pharmacokinetics of the two routes of administration is unclear.Objective The goal of this study was to investigate the level of amphotericin B in cornea and aqueous humor of rabbits after administration of AMB via three different routes. Methods Forty-five healthy domestic rabbits were randomly divided into three groups. 1% amphotericin B of 10 μg was intrastromally or intracamerally injected into 15 rabbits, respectively,in group A and group B. Topical 0. 25% amphotericin B was topically administered to the eyes with corneal epithelial debridement (group C). Experimental animals were sacrificed and the corneas and aqueous humor samples were obtained for the detection of levels of amphotericin B at 30 minutes,6 hours, 1 day,3 and 7 days by high-performance liquid chromatography (HPLC). Results Calibration curves were linear over the range of 0. 10-100. 00 mg/L. The concentration of 0. 10 mg/L was the lowest quantifiable limit. The recovery of amphotericin B ranged from 89. 1% -95.7% from aqueous humor samples and 81.4% -83.6% from the cornea samples. After a single injection,effective drug levels were achieved and maintained for 7 days in cornea in group A, exceeding the minimum inhibitory concentration at which 90% of isolates are inhibited (MIC90) for a wide spectrum of fungi and molds with significant differences in comparison with group B and group C ( P＜0. 05 ). Effective drug levels were achieved in the aqueous humor in group B at 30 minutes after a single injection, but drug levels decreased dramatically within 6 hours. The evident differences were found between group B and group A or group C (P＜ 0.05). A considerable amount of amphotericin B was detected in the cornea and aqueous humor in group C within 1 day.Conclusion Effective high drug levels can be reached in rabbit cornea and aqueous humor after intrastromal and intracameral injection, respectively. Penetration of topical amphotericin B was greatly elevated after epithelial debridement. Key words: Amphotericin B; Chromatography; High pressure liquid; Pharmacokinetics

The Effects of Intrastromal Voriconazole Injection and Topical Voriconazole in the Treatment of Recalcitrant Fusarium Keratitis

To describe the course and outcome in 3 patients with recalcitrant fungal keratitis treated with intrastromal voriconazole injection and topical voriconazole application. The present study was an interventional case series. A 50 μg/0.1 mL solution of voriconazole was injected into the corneal stromal tissue around the corneal ulcer, and 1% topical voriconazole was added to the therapeutic regimen if the ulcer failed to respond to 5% topical natamycin hourly and oral ketoconazole twice per day. The infiltration and epithelial defect size were measured at each visit using a slit-lamp biomicroscope. Anatomical outcomes were assessed. A dramatic therapeutic response was observed in 2 patients. An amniotic membrane transplantation using cyanoacrylate glue was required to seal the microperforation in a patient with a chemical burn superinfected with Fusarium. Intrastromal injection of voriconazole together with topical voriconazole effectively reduced the infiltration size and controlled the infection in patients with Fusarium keratitis. However, continued application of the topical medication is critical for a favorable outcome of treatment.

Evaluation of intrastromal voriconazole injection in recalcitrant deep fungal keratitis: case series

AimTo evaluate the efficacy of intrastromal voriconazole, as a modality of treatment for management of recalcitrant fungal keratitis.MethodsTwelve patients of smear and/or culture positive fungal keratitis not responding to topical...

Current progression in pharmacotherapeutics of fungal keratitis

Fungal keratitis is the first common infectious corneal disease and has become the main cause of blindness in China.Along with the intensive explore for the pathogenic mechanisms,the significant progress has been achieved in the pharmacotherapeutics.For lowering its blindnessrate,it is imperative to the study on increasing therapeutic option and enhancing therapeutic efficacy.This review summarizes the current advance in clinical use in ophthalmology of novel antifungal agents,including new azoles such as voriconazole and posaconazole,and echinocandins such as caspofungin and micafungin.This article also reviews the progress of administration routes for the management of recalcitrant fungal keratitis,including subconjunctival,interstromal,intracameral and intravitreal injection. Key words: keratitis; eye infections; fungus; pharmacotherapeutics

Evaluation of Intrastromal Injection of Voriconazole as a Therapeutic Adjunctive for the Management of Deep Recalcitrant Fungal Keratitis

To evaluate the role of intrastromal injection of voriconazole in the management of deep recalcitrant fungal keratitis. Interventional case series. Cornea services at a tertiary care teaching hospital. Three eyes of three patients with deep stromal recalcitrant fungal keratitis not responding to topical antifungal medications. Intervention Procedure: Voriconazole 50 micrograms/0.1 ml was injected circumferentially around the fungal abscess in the corneal stroma as an adjunctive to the topical antifungal therapy. Main outcome measure was a reduction in size of the abscess and resolution of the infection. Before the intracorneal injection, all three eyes had gradually worsening lesions on topical medications. After the intervention, a faster reduction in the size of corneal infiltration was documented and a complete resolution of the ulcers was seen within three weeks in all cases. Targeted delivery of voriconazole by intracorneal injection may be a safe and effective way to treat cases of deep-seated recalcitrant fungal keratitis responding poorly to conventional treatment modalities.