Keratitis treatment has become more complicated due to the emergence of bacterial or fungal pathogens with enhanced antibiotic resistance. The pharmaceutical applications of N-heterocyclic carbene complexes have received remarkable attention due to their antimicrobial properties. In this paper, the new precursor, 3,3′-(p-phenylenedimethylene) bis{1-(2- methyl-allyl)imidazolium} bromide (1a) and its analogous PF6 salt (1b) were synthesized. Furthermore, silver(I) and gold(I) -N-heterocyclic carbene (NHC) complexes [Ag2LBr2/Au2LBr2; 2a/3a], [(Ag2L2)(PF6)2/(Au2L2)(PF6)2; 2b/3b] were developed from their corresponding ligands. All compounds were screened for their antimicrobial activities against multiple keratitis-associated human eye pathogens, including bacteria and fungi. Complexes 2a and 3a showed highest activity, and the effectiveness of 3a was also studied, focusing eradication of pathogen biofilm. Furthermore, the structures of 1a, 2a and 3b were determined using single crystal X-ray analysis, 2b and 3a were optimized theoretically. The mechanism of action of 3a was evaluated by scanning electron microscopy and docking experiments, suggesting that its target is the cell membrane. In summary, 3a may be helpful in developing antimicrobial therapies in patients suffering from keratitis-associated eye infections caused by multidrug-resistant pathogens.

BackgroundCorneal diseases are one of the major causes of visual loss and blindness, second only to cataract. Amongst corneal diseases, microbial keratitis is a major blinding disease. In some countries, fungal keratitis accounts for almost 50% of patients with culture-proven microbial keratitis.AimThis study was conducted to determine the epidemiological characteristics of fungal keratitis in an urban population of West Bengal and identify the specific pathogenic organisms.MethodsThe charts of patients with microbial keratitis who attended the Cornea Services of Priyamvada Birla Aravind Eye Hospital from January to December 2008 were retrospectively reviewed. Records of patients with 10% KOH mount and culture positive fungal keratitis were analyzed for epidemiological features, laboratory findings and treatment outcomes.ResultsOf the 289 patients of microbial keratitis included in the study, 110 patients (38.06%) were diagnosed with fungal keratitis (10% KOH mount positive). Of the 110 patients, 74 (67.27%) fitted the study inclusion criteria (10% KOH mount and culture positive). Forty five of 74 patients (60.81%) in the study group were in the older age group (>50 years). Ocular trauma in 35 cases (47.29%) was identified as a high risk factor and vegetative injuries in 17 cases (22.97%) were identified as a significant cause for fungal keratitis. Maximum organism source was from corneal scrapings in 41 cases (55%). The predominant fungal species isolated was Aspergillus sp (55.40%) followed by Candida albicans 14 cases (18.91%) and Fusarium sp. in 8 cases (10.81%). Agricultural activity related ocular trauma was the principal cause of mycotic keratitis and males were more commonly affected. Thirty of 74 cases (40.55%) of the culture positive patients healed with corneal scar formation with medical treatment whereas 44 cases (59.45%) required therapeutic keratoplasty.ConclusionFungal keratitis is an important cause of microbial keratitis with injury to the cornea being a leading predisposing factor. Although Aspergillus sp. was implicated in most of the patients in our study population, Candida sp. were found in higher numbers than previously reported. Keratitis caused by filamentous fungi responds adequately to medical management. Therapeutic keratoplasty continues to remain an important treatment modality in infections with Candida sp. Early diagnosis with prompt identification of the pathogenic organism is mandatory to initiate appropriate therapy and thereby reduce morbidity.

A case report and review of literature is reported of a rare case of fungal keratitis from eastern India. A 32-year-old woman with a history of vegetative trauma presented with keratitis in left eye. Microbiological examination of corneal scraping showed refractile hyphae with aseptate branching filaments and black pigmented colonies on multiple solid agar medium. Organism was identified from culture using D1/D2 region of LSU (Large Sub Unit: 28S rDNA)-based molecular technique. PCR amplified a band with a sequence that was 100 % homologous with Lasiodiplodia theobromae. The organism was susceptible to amphotericin B and voriconazole and demonstrated resistance to itraconazole and fluconazole. A therapeutic keratoplasty was performed following non-responsiveness to initial topical voriconazole (2 %) therapy. Recurrence in graft was controlled with topical voriconazole and intracameral amphotericin B. However, the graft failed at the end of 3 months. L. theobromae is a rare cause of fungal keratitis. Management of these cases is difficult, often involving surgical procedures.

The best of our knowledge, this is the first reported case of keratitis caused by the rare fungus S. commune. Management of these cases is difficult, and surgical procedures may be needed.

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