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Mycotic Keratitis Caused by Dematiaceous Fungi
Published in Mahendra Rai, Marcelo Luís Occhiutto, Mycotic Keratitis, 2019
Javier Araiza, Andrés Tirado-Sánchez, Alexandro Bonifaz
Mycotic keratitis which is a fungal infection with global distribution could be caused by a divergent set of fungi. Timely diagnosis of disease and the prompt initiation of therapy results in the improved prognosis of MK. Dematiaceous fungi that cause MK can be identified by routine laboratory mycological techniques. However, the correct identification should be made by molecular techniques due to changes and frequent taxonomic reclassifications. Bio-microscopy with slit-lamp as well as mycological studies are the most commonly used diagnostic strategies. PCR-based methods may be helpful for rapid detection and/or identification of fungi in corneal specimen. Further studies are required for evaluation and standardization of these methods. Topical natamycin is the first choice of treatment; however, different schemes combining topical and systemic antifungals have been proposed. Drug resistance is an important factor that negatively affects the treatment outcome. In vitro susceptibility could be used to provide useful data for treatment selection; however, due to the severity of MK, empiric antifungal treatment is frequently chosen with better outcome.
Novel methods of antifungal administration
Published in Mahmoud A. Ghannoum, John R. Perfect, Antifungal Therapy, 2019
At present, natamycin (a polyene antifungal) is the only topical agent commercially available and FDA-approved for the treatment of ocular fungal infections [192–194]. In one study, natamycin 5% eye drops was compared with itraconazole 1% eye drops in 100 patients with fungal keratitis due to a variety of pathogens, including Fusarium, Aspergillus, and Curvularia [192]. Overall, favorable response rates were seen in 72% and 60% of natamycin and itraconazole-treated patients, respectively. In the subset of patients with fungal keratitis due to Fusarium spp, 19/24 (79%) and 8/18 (44%) demonstrated a favorable response, respectively (p < 0.02). Natamycin has become a treatment option primarily for the treatment of keratitis due to filamentous fungi [195]. Natamycin 5% ophthalmic suspension is approved for use in the US for the treatment of fungal blepharitis, conjunctivitis, and keratitis. Topical administration of other polyene antifungals has also been described. Amphotericin B eye drops have been used in the treatment of a variety of fungal pathogens such as Aspergillus, Candida, Curvalaria lunata, Phialophora, Gibberella, Alternaria, Scopularisopsis brevicaulis, Rhinosporidiosis, Macrophoma, and Fusarium [196–201]. Solutions containing 0.5–1.5 mg/mL of amphotericin B were administered every 30 minutes to 1 hour [196–201].
Natamycin
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Nenad Macesic, John R. Wingard
Natamycin has a wide spectrum of antifungal activity. Yeasts such as Cryptococcus neoformans, Candida albicans, and other Candida spp. are sensitive (Spierer et al., 2015). Filamentous fungi, such as Aspergillus spp., Acremonium spp., and Cunninghamella spp., are sensitive, with mean inhibitory concentrations (MICs) less than 4 mg/l. Fusarium spp. and Pseudallescheria boydii are also susceptible to natamycin (Reuben et al., 1989; Rotowa et al., 1990; Al-Hatmi et al., 2015b; Homa et al., 2013). Natamycin topical drops at a concentration of 50 mg/ml were effective in the rabbit model of experimental keratitis due to Aspergillus fumigatus (Garcia de Lomas et al., 1985).
Clinical Outcomes of Rose Bengal Mediated Photodynamic Antimicrobial Therapy on Fungal Keratitis with Their Microbiological and Pathological Correlation
Published in Current Eye Research, 2022
Bhupesh Bagga, Savitri Sharma, Lalit Kishore Ahirwar, Esther Sheba, Pravin Krishna Vaddavalli, Dilip K Mishra
Seven eyes of 7 patients were treated and evaluated in the study. There were five males and two females with an average age of 49 ± 12 years (Table 1). The average duration of onset of infection was 13 ± 12.2 days. There were 5 cases that were associated with a history of trauma with dust or wooden material while on work. At the time of presentation, 5 out of 7 patients were using Natamycin 5% topically for 19.75 (±12.7) days. The average maximum vertical and horizontal diameters were 4.12 ± 0.55 and 3.99 ± 1.19 mm, and stromal depth hyperreflectivity measured with anterior segment optical coherence tomography was 283 ± 75.27µ. Figure 1 illustrates the OCT image of four patients at the time of presentation. This was not available for the remaining three patients. Six of seven patients had hypopyon of an average of 0.87 mm. Out of 7 cases, three were caused by Fusarium sp. (2 were F. solani, 1 Fusarium species) and three by Aspergillus flavus, and 1 case was of Acremonium species. The median duration of performing PDAT after a presentation to the clinic was three days (1.5–8.5 days). Three patients had two sessions (4th and 7th-day post-presentation), and the other four received a single session of PDAT.
Reduced administration frequency for the treatment of fungal keratitis: a sustained natamycin release from a micellar solution
Published in Expert Opinion on Drug Delivery, 2020
Yiyuan Guo, Fatemeh Karimi, Qiang Fu, Greg. G. Qiao, Hong Zhang
In addition, the inhibition diameter of 9.65 ± 0.65 mm and 14.19 ± 1.08 mm were observed for PBS formulation (Nat group) at dilutions of 25 μg and 50 μg, respectively. Slightly smaller zone of inhibitions 9.09 ± 0.66 mm and 13.85 ± 0.95 mm were found after 24 h of incubation with micellar formulation at natamycin dilutions of 25 μg and 50 μg in PBS, respectively (Figure 7(b)). From the obtained results of the MIC values and the diameter of inhibition zone, a similar but slightly lower anti-fungal activity of micellar formulation was observed when compared to PBS formulation. Micelle, as a drug carrier, has no anti-fungal ability to Candida albicans. Hence, it can be concluded that all fungal inhibitions resulted from the natamycin released from micelle. Slightly lower antifungal activity of micellar formulation may be attributed to the restriction by the micelle structure and the incomplete release of drug from the micelle.
In Vitro Efficacy of Chlorhexidine and a riboflavin/UVA Combination on Fungal Agents of Keratitis
Published in Current Eye Research, 2020
Zeynep Kunt, Meltem Yağmur, Hazal Kandemir, Inan Harbiyeli, Elif Erdem, Ayşe Kalkancı, G.Sybren De Hoog, Macit Ilkit
Although 0.02% CHX has previously been employed in some cases of keratitis, data are limited regarding its effectiveness for treating mycotic keratitis.23,35–37 When investigating the efficacy of 0.02% CHX in treating mycotic keratitis, Rahman et al.37 reported that treatment responses were similar to treatment effects using natamycin. In another report, a patient was successfully treated with a combination of 0.02% CHX and AMB.31 Similarly, we previously reported that a case of mycotic keratitis caused by F. solani sensu stricto (FSSC5) was completely resolved after a combined treatment of 2.5 mg/mL AMB and 0.02% CHX gluconate.38 In our current in vitro study, we found that 0.02% CHX effectively prevented the growth of filamentous fungi that cause keratitis. Nonetheless, our study was limited in some respects: (1) our selection of the F. solani strain was unfortunate because it was susceptible to VRC (even though VRC may exhibit strain-dependent susceptibility), FSSC strains are usually resistant to a wide variety of antifungal drugs,39 (2) we tested the relatively few fungal isolates, and (3) we did not obtain data on the clinical outcomes and toxicities of the examined treatment methods. These limitations should be addressed in future studies.