Antifungal drug resistance in molds: Clinical and microbiological factors

Alcàzar-Fuoli, Laura; Rodríguez-Tudela, Juan Luis; Mellado, Emilia

doi:10.1007/s12281-008-0006-2

Cited by 9 publications

(8 citation statements)

References 53 publications

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“…All four azoles tested (voriconazole, isavuconazole, posaconazole and itraconazole) showed excellent activity against A. flavus isolates. The MIC results were lower for posaconazole and itraconazole as compared with voriconazole and isavuconazole and were in agreement with other studies 15,21,23–25,28,31–34 . Posaconazole was the most potent azole (GM MIC of 0.123 mg l −1 ) followed by itraconazole, isavuconazole and voriconazole.…”

Section: Discussionsupporting

confidence: 91%

“…Only three isolates had an increased MIC of 2 mg l −1 which was even higher when repeated by E‐test (8 mg l −1 ). Overall, A. flavus strains were less susceptible than reported for A. fumigatus and the results were similar to other studies reported for A. flavus 15,21,23–25 . Echinocandins have moderately good activity against A. flavus strains.…”

Section: Discussionsupporting

confidence: 88%

“…Overall, A. flavus strains were less susceptible than reported for A. fumigatus and the results were similar to other studies reported for A. flavus. 15,21,[23][24][25] Echinocandins have moderately good activity against A. flavus strains. In this study anidulafungin (GM MEC of 0.004 mg l )1 ) was the most active echinocandin followed by micafungin (GM MEC of 0.025 mg l )1 ) and caspofungin (GM MEC of 0.506 mg l )1 ).…”

Section: Discussionmentioning

confidence: 99%

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In vitro susceptibility of 188 clinical and environmental isolates of Aspergillus flavus for the new triazole isavuconazole and seven other antifungal drugs

Shivaprakash

Geertsen

Chakrabarti

et al. 2011

Mycoses

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Recently isavuconazole, an experimental triazole agent, was found to be active against Aspergillus species. As Aspergillus flavus is the second-most common Aspergillus species isolated from human infection and the fungus has not been widely tested against the drug, we studied a large collection of clinical (n = 178) and environmental (n = 10) strains of A. flavus against isavuconazole and compared the results with seven other Aspergillus-active antifungal agents (some of them triazoles, others echinocandins or polyene antifungals: voriconazole, posaconazole, itraconazole, caspofungin, anidulafungin, micafungin and amphotericin B) using Clinical and Laboratory Standards Institute methods. Strains with high minimal inhibitory concentrations (MICs) were tested by E-test as well. The strains were collected from two different geographical locations (India and the Netherlands). Three isolates (1.6%) had high MIC (2 mg l(-1) by microbroth dilution and 8 mg l(-1) by E-test) for amphotericin B. Isavuconazole showed good activity against A. flavus strains with MIC(50) and MIC(90) values of 1 mg l(-1). As compared with voriconazole (the drug recommended for primary therapy of aspergillosis), isavuconazole had better activity (99.5% of strains had MIC of ≤ 1 mg l(-1) for isavuconazole, compared to 74% of strains with same MIC for voriconazole). All strains were, following recently proposed clinical breakpoints, susceptible for the triazoles tested except three strains, which had MICs of 4 mg l(-1) for voriconazole. Testing these strains with high MIC by E-test, gave results of 0.5-2 mg l(-1). Posaconazole had the lowest MIC(50) and MIC(90) of 0.125 mg l(-1) and 0.25 mg l(-1), respectively. Among echinocandins, 97% of strains had a minimum effective concentration (MEC) of ≤ 0.5 mg l(-1) for caspofungin, and all strains had a MEC of ≤ 0.016 mg l(-1) and ≤ 0.125 mg l(-1) for anidulafungin and micafungin, respectively.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

In vitro susceptibility of 188 clinical and environmental isolates of Aspergillus flavus for the new triazole isavuconazole and seven other antifungal drugs

Shivaprakash

Geertsen

Chakrabarti

et al. 2011

Mycoses

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“…Based on the variBased on the various clinical experiences [6,7,29,[43][44][45][46][47]77,106,[108][109][110][111][112][113] and of extrapolation from yeasts, susceptibility testing could be performed when:…”

Section: In Vitro Cross-resistancementioning

confidence: 99%

In vitro Susceptibility Testing in Aspergillus Species: An Update

Lass‐Flörl¹

2010

Future Microbiol.

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Aspergillus species are the most common causes of invasive mold infections in immunocompromised patients. The introduction of new antifungal agents and recent reports of resistance emerging during treatment of Aspergillus infections have highlighted the need for in vitro susceptibility testing. Various testing procedures have been proposed, including macro- and micro-dilution, disk diffusion, Etest (AB Biodisk, Sweden) and other commercial tests. Although Aspergillus species are generally susceptible to various compounds, intrinsic and acquired resistance has been documented. Amphotericin B has limited activity against Aspergillus terreus and Aspergillus nidulans. Not surprisingly, continued use of azole-based drugs has the undesirable consequence of elevating the resistance of subsequent isolates from these patients. Several species in the Aspergillus fumigatus complex appear to be resistant to azoles; there is evidence of in vitro and in vivo correlation. Each in vitro susceptibility testing method has its own advantages and disadvantages. Etest is easy to perform and use on a daily basis, yet it is expensive. Disk diffusion is the most attractive alternative method to date, yet we lack sufficient data for aspergilli. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the Clinical Laboratory Standard Institute (CLSI) have produced reproducible reference testing methods. This article reviews the available methods for antifungal susceptibility testing in Aspergillus spp. as well as the scant data regarding the clinical implications of in vitro testing.

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“…Aspergillus fumigatus, however, possesses two distinct but related CYP51 proteins encoded by cyp51A and cyp51B (Mellado et al, 2001). Targeted disruption of the cyp51 genes showed differential features of the CYP51 enzymes in that CYP51A was responsible for the sensitivity to azoles, and CYP51B was associated with A. fumigatus growth rate and shape maintenance (Alcazar-Fuoli et al, 2007;Mellado et al, 2005). Genomic studies revealed the existence of three paralogous cyp51 genes in F. graminearum, but to date, their functions have not been investigated.…”

Section: Introductionmentioning

confidence: 99%