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Role of Antifungal Susceptibility Testing in Non-Aspergillus Invasive Mold Infections.

ABSTRACT: No clinical breakpoints are available to delineate antifungal drug efficacy in non-Aspergillus invasive mold infections (NAIMIs). In this analysis of 39 NAIMI episodes, the MIC of the first-line antifungal drug was the most important predictor of therapeutic response. For amphotericin B, an MIC of ?0.5 ?g/ml was significantly associated with better 6-week outcomes.

SUBMITTER: Lamoth F

PROVIDER: S-EPMC4879309 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Role of Antifungal Susceptibility Testing in Non-Aspergillus Invasive Mold Infections.

Lamoth Frédéric F Damonti Lauro L Alexander Barbara D BD

Journal of clinical microbiology 20160323 6

No clinical breakpoints are available to delineate antifungal drug efficacy in non-Aspergillus invasive mold infections (NAIMIs). In this analysis of 39 NAIMI episodes, the MIC of the first-line antifungal drug was the most important predictor of therapeutic response. For amphotericin B, an MIC of ≤0.5 μg/ml was significantly associated with better 6-week outcomes. ...[more]

PMID: 27008871

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Project description:Non-Aspergillus molds including Mucorales, Fusarium, and Scedosporium, etc. are emerging pathogens leading to higher mortality in immunocompromised patients. Fifty-two isolates of genetically confirmed non-Aspergillus molds representing 16 species from 8 genera were collected to evaluate the performance of the Bruker matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) in identification of non-Aspergillus molds. Antifungal susceptibilities were determined through the Clinical & Laboratory Standards Institute (CLSI) M38-A2 broth microdilution method and the Sensititre YeastOne colorimetric method. Bruker MALDI-TOF MS identified 57.7% (30/52) of isolates cultured in broth and 15.4% (8/52) of isolates cultured on solid agar media to the species level, respectively, according to standard interpretation criteria. Lowering the species level cut-off value (COV) from ≥2.0 to ≥1.7 could improve the MALDI-TOF MS species-level identification rate to 67.3% (38/52) for isolates cultured on solid media, with a slight increase of false identification rate of 2.6% (1/38). Amphotericin B was the most in vitro fungistatic-active agent for 98.1% (51/52) of the tested non-Aspergillus molds, with minimum inhibitory concentrations (MICs) of ≤2 μg/mL. The susceptibilities to triazoles varied, with MICs of 0.12 to >16 μg/mL among different species of non-Aspergillus molds. The correlation between the CLSI method and Sensititre YeastOne on antifungal susceptibility testing of non-Aspergillus molds was good, with essential agreement (EA) rates of >90% for triazoles and echinocandins except amphotericin B, which had a lower EA rate of 84.6%. In conclusion, a favorable performance of the Bruker MALDI-TOF MS in identification of clinical non-Aspergillus isolates directly inoculated on solid agar media could be achieved with the adoption of alternative interpretation criteria. Antifungal susceptibility testing is important for non-Aspergillus molds, especially when information on triazole susceptibility is required, and the Sensititre YeastOne is a practical and reliable method to determine antifungal susceptibilities of non-Aspergillus molds.

Project description:Molds are ubiquitous in the environment, and immunocompromised patients are at substantial risk of morbidity and mortality due to their underlying disease and the resistance of pathogenic molds to currently recommended antifungal therapies. This combination of weakened-host defense, with limited antifungal treatment options, and the opportunism of environmental molds renders patients at risk and especially vulnerable to invasive mold infections such as Aspergillus and members of the Order Mucorales. Currently, available antifungal drugs such as azoles and echinocandins, as well as combinations of the same, offer some degree of efficacy in the prevention and treatment of invasive mold infections, but their use is often limited by drug resistance mechanisms, toxicity, drug-drug interactions, and the relative paucity of oral treatment options. Clearly, there is a need for agents that are of a new class that provides adequate tissue penetration, can be administered orally, and have broad-spectrum efficacy against fungal infections, including those caused by invasive mold organisms. Ibrexafungerp, an orally bioavailable glucan synthase inhibitor, is the first in a new class of triterpenoid antifungals and shares a similar target to the well-established echinocandins. Ibrexafungerp has a very favorable pharmacokinetic profile for the treatment of fungal infections with excellent tissue penetration in organs targeted by molds, such as the lungs, liver, and skin. Ibrexafungerp has demonstrated in vitro activity against Aspergillus spp. as well as efficacy in animal models of invasive aspergillosis and mucormycosis. Furthermore, ibrexafungerp is approved for use in the USA for the treatment of women with vulvovaginal candidiasis. Ibrexafungerp is currently being evaluated in clinical trials as monotherapy or in combination with other antifungals for treating invasive fungal infections caused by yeasts and molds. Thus, ibrexafungerp offers promise as a new addition to the clinician's armamentarium against these difficult-to-treat infections.

Dataset Information

Role of Antifungal Susceptibility Testing in Non-Aspergillus Invasive Mold Infections.

Publications

Role of Antifungal Susceptibility Testing in Non-Aspergillus Invasive Mold Infections.

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