Molecular characterization of drug-resistant and drug-sensitive Aspergillus isolates causing infectious keratitis

Nayak, Niranjan; Satpathy, Gita; Prasad, Sujata; Titiyal, Jeewan S; Pandey, RM; Vajpayee, Rasik B

doi:10.4103/0301-4738.83614

Cited by 16 publications

(13 citation statements)

References 21 publications

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“…6-13,16-28 These studies used different methods to report MIC (MIC 50 , MIC 90 , and range) and demonstrated variable MICs. The natamycin and voriconazole MIC 50 and MIC 90 found in our study for Fusarium isolates were within the range of published values for F. solani and for all Fusarium species.…”

Section: Resultsmentioning

confidence: 99%

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In Vitro Susceptibility of Filamentous Fungal Isolates From a Corneal Ulcer Clinical Trial

Lalitha

Sun

Prajna

et al. 2014

American Journal of Ophthalmology

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Purpose To describe the minimum inhibitory concentration (MIC) of fungal isolates to natamycin and voriconazole, and to compare these MICs to previous ocular susceptibility studies. Design Experimental laboratory study using isolates from a randomized clinical trial. Methods The Mycotic Ulcer Treatment Trial I was a randomized, double-masked, multicenter trial comparing topical natamycin and voriconazole for fungal keratitis treatment. Susceptibility testing to natamycin and voriconazole were performed according to Clinical and Laboratory Standards Institute methods. The relationship between organism and MIC was assessed. A literature review was performed to compare results to previous ocular susceptibility studies. Results Of the 323 patients enrolled in the trial, MICs were available for 221 (68%). Fusarium (N=126) and Aspergillus species (N=52) were the most commonly isolated organisms. MICs to natamycin and voriconazole were significantly different across all genera (P<0.001). The MIC median (MIC50) and 90th percentile (MIC90) for natamycin were equal to or higher than voriconazole for all organisms, except Curvularia species. Compared to other organisms, Fusarium species isolates had the highest MICs to voriconazole and A. flavus isolates had the highest MICs to natamycin. Our results were similar to previous reports except the voriconazole MIC90 against Aspergillus species was 2-fold higher and the natamycin MIC90 against A. fumigatus was 4-fold higher in our study. Conclusion In this large susceptibility study, Fusarium isolates were least susceptible to voriconazole and A. flavus isolates were least susceptible to natamycin when compared to other filamentous fungi. In the future, susceptibility testing may help guide therapy if performed in a timely manner.

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Section: Resultsmentioning

confidence: 99%

“…12,33, 34 Prior in vitro susceptibility studies have demonstrated that A. flavus and A. fumigatus have MICs that are highest for natamycin, followed by amphotericin B, and then voriconazole, confirming that voriconazole may be most effective against Aspergillus species (Table 3). 6,7,10-12,18,19,21,27,28 …”

Section: Discussionmentioning

confidence: 99%

In Vitro Susceptibility of Filamentous Fungal Isolates From a Corneal Ulcer Clinical Trial

Lalitha

Sun

Prajna

et al. 2014

American Journal of Ophthalmology

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“…The epidemiological pattern of fungal keratitis varies significantly from country to country and even from region to region. The limited availability of antifungal drugs and the lack of appropriate response lead to blindness in a high number of patients [6,7]. The level of susceptibility of Aspergillus strains to different antifungal compounds may vary from one isolate to another [6,7].…”

Section: Introductionmentioning

confidence: 99%

“…The limited availability of antifungal drugs and the lack of appropriate response lead to blindness in a high number of patients [6,7]. The level of susceptibility of Aspergillus strains to different antifungal compounds may vary from one isolate to another [6,7]. The current knowledge on antifungal susceptibilities is mainly based on the Western literature and local data available in India are inadequate.…”

Section: Introductionmentioning

confidence: 99%

Epidemiology ofAspergilluskeratitis at a tertiary care eye hospital in South India and antifungal susceptibilities of the causative agents

Palanisamy

Varga

Kocsubé

et al. 2012

Mycoses

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Summary In recent years, Aspergillus species are reported frequently as aetiological agents of fungal keratitis in tropical countries such as India. Our aim was to evaluate the epidemiological features of Aspergillus keratitis cases over a 3‐year period in a tertiary eye care hospital and to determine the antifungal susceptibilities of the causative agents. This study included culture proven Aspergillus keratitis cases diagnosed between September 2005 and August 2008. Data including prevalence, predisposing factors and demography were recorded, the isolates were identified by morphological and molecular methods and the minimum inhibitory concentration values of antifungal agents towards the isolates were determined by the microdilution method. Two hundred Aspergillus isolates were identified among 1737 culture proven cases. Most of the aspergilli (75%) proved to be A. flavus, followed by A. fumigatus (11.5%). Sixteen (8%) isolates belonged to species that are recently identified causative agents of mycotic keratitis. Most of the infected patients (88%) were adults ranging from 21 to 70 years of age. Co‐existing ocular disease was confirmed in 16.5% of the patients. Econazole, clotrimazole and ketoconazole were notably active against A. flavus. Aspergillus keratitis is a significant problem in patients with ocular lesions in South‐Indian States, warranting early diagnosis and initiation of specific antifungal therapy to improve outcome.

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“…The Fusarium solani species complex (FSSC) and Aspergillus flavus species complex (AFSC) are two predominant ocular fungal pathogens and are thought to be particularly virulent, more resistant to antifungals, and have worse outcomes than other species of Fusarium and Aspergillus in China and in many other parts of the world (4)(5)(6)(7)(8)(9)(10). Keratomycosis is notoriously difficult to treat.…”

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confidence: 99%

Rifampin Enhances the Activity of Amphotericin B against Fusarium solani Species Complex and Aspergillus flavus Species Complex Isolates from Keratitis Patients

Zhou

Gao

et al. 2017

Antimicrob Agents Chemother

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The in vitro activities of amphotericin B in combination with rifampin were assessed against 95 ocular fungal isolates. The interactions between amphotericin B and rifampin at 4, 8, 16, and 32 g/ml were synergistic for 11.8%, 51.0%, 90.2%, and 94.1%, respectively, of Fusarium solani species complex isolates and for 13.6%, 45.5%, 93.2%, and 95.5%, respectively, of Aspergillus flavus species complex isolates. Antagonism was never observed for the amphotericin B-rifampin combinations.KEYWORDS amphotericin B, Aspergillus flavus species complex, Fusarium solani species complex, rifampin, synergistic activity, fungal keratitis K eratomycosis is a major cause of vision loss in developing countries like China because of higher incidence and the unavailability of effective antifungal agents (1-3). The Fusarium solani species complex (FSSC) and Aspergillus flavus species complex (AFSC) are two predominant ocular fungal pathogens and are thought to be particularly virulent, more resistant to antifungals, and have worse outcomes than other species of Fusarium and Aspergillus in China and in many other parts of the world (4-10). Keratomycosis is notoriously difficult to treat. Amphotericin B is one of the most commonly used topical agent to treat keratomycosis (11, 12); however, nonsusceptibility to amphotericin B has been recently reported for filamentous fungi (13-16), and some studies have shown that the response rates to amphotericin B for Fusarium keratitis and Aspergillus keratitis are 56% and 27%, respectively (11,17,18). Therefore, there is an urgent need for new approaches to manage amphotericin B-nonsusceptible filamentous fungi. One possible approach is to combine amphotericin B with other antimicrobial agents (12). Amphotericin B and natamycin are often combined in the treatment of keratomycosis. However, a study by Lalitha et al. has shown that amphotericin B and natamycin are not synergistic in vitro against Fusarium and Aspergillus species isolated from keratitis (19). Two small clinical studies have shown the potential of an amphotericin B-rifampin combination to improve outcomes in keratomycosis (20,21). This combination therapy may be an option for patients with amphotericin B-nonsusceptible keratomycosis. The aim of this study was to investigate the potentiation of the antifungal activity of amphotericin B by rifampin with clinically relevant concentrations against FSSC and AFSC isolates in vitro.

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Molecular characterization of drug-resistant and drug-sensitive Aspergillus isolates causing infectious keratitis

Cited by 16 publications

References 21 publications

In Vitro Susceptibility of Filamentous Fungal Isolates From a Corneal Ulcer Clinical Trial

In Vitro Susceptibility of Filamentous Fungal Isolates From a Corneal Ulcer Clinical Trial

Epidemiology ofAspergilluskeratitis at a tertiary care eye hospital in South India and antifungal susceptibilities of the causative agents

Rifampin Enhances the Activity of Amphotericin B against Fusarium solani Species Complex and Aspergillus flavus Species Complex Isolates from Keratitis Patients

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