Classification, Drug Sensitivity Test, And Outcome In A Fungal Keratitis Clinical Trial

Objective To identify the epidemiology and causative fungi of fungal keratitis, test their susceptibility to antifungal agents with the disk diffusion method and study the relationship between the organisms, the inhibition zones and the clinical outcomes. To identify risk factors that can serve as prognostic indicators of clinical outcome in cases of fungal keratitis.Methods Patients with fungal keratitis from 2013 to 2015 in Department of Ophthalmology were included in this study. Slit-lamp examination, corneal scraping examination, and confocal microscopy were used to diagnose. Pathogenic fungi were isolated by corneal scraping, identified by fungal cultivation and subjected to drug sensitivity tests conducted with the disk diffusion method. The patients were treated initially with voriconazole, terbinafine and natamycin eye drops for one week. Further treatment continued using the most effective drug according to the drug sensitivity results. If poor results of the combination antifungal drug treatment,according to the focus of the patient, choose corneal lesion resection combined with conjunctival flap transplantation, lamellar corneal transplantation or penetrating corneal transplantation for treatment. The patients were followed up every week until three months after cured. Describe the epidemiology characterization of fungal keratitis. The inhibition zones of fungi cultured with voriconazole, terbinafine, natamycin, amphotericin and ketoconazole were compared. The relationship between inhibition zones and organism, organism and treatment results measure, and each treatment results measure and inhibition zones were evaluated. The relationship between age, gender, history of trauma, genera, drug sensitivity test, lesion characteristics, and clinical outcome of fungal keratitis were analyzed.Results 1.19 ~ 59 year old labor population was the high incidence of population for fungal keratitis. The history of trauma was the main risk factors for middle-aged and young groups. And the main risk factors of elderly patients were ocular surface disease and history of ocular surgery. Of 1087 patients, 54.1% and 19.59% were infected with Aspergillus and Fusarium, respectively. 2. The size of the inhibition zones of Aspergillus spp., Fusarium spp. and other fungal genera differed significantly in response to voriconazole, terbinafine and natamycin. Keratitis patients infected with Aspergillus keratitis had the worst outcome. The medication cure rate of Aspergillus keratitis was the lowest(64.94%). The medication healing rate of treatment under the guidance of drug sensitive test were higher than that without drug sensitive test(P<0.00). Age, sex, trauma were not significantly correlate with clinical outcome(P>0.05). Size of infiltration, hypopyon, number of sensitive drugs, and pathogenic fungi were significantly correlated with clinical outcome(P<0.05). The inhibition zone associated with natamycin correlated significantly with the clinical outcome of fungal keratitis, but no other such correlations were found for the other drugs tested.Conclusion 1. Aspergillus and Fusarium were the predominant pathogenic genera causing fungal keratitis in our patients. Ocular surface disease and history of trauma and ocular surgery were the main risk factors for fungal keratitis. 2. Among the causative fungi, infections due to Aspergillus spp. were associated with the worst outcomes. In vitro drug sensitivity test can guide clinical drug treatment of fungal keratitis. 3. The inhibition zones of fungal isolates in response to natamycin significantly correlated with the treatment outcomes of keratitis. Specifically, the smaller the natamycin inhibition zone, the lower the probability that the fungal keratitis had been eliminated. Large size of infiltration, presence of hypopyon, infection with Fusarium.spp or Aspergillus.spp and resistance to those drugs in vitro were the main risk factors for clinical outcome of fungal keratitis.