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Michael A. Pfaller - One of the best experts on this subject based on the ideXlab platform.
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Utility of Antifungal Susceptibility Testing and Clinical Correlations
Interactions of Yeasts Moulds and Antifungal Agents, 2011Co-Authors: Daniel J. Diekema, Michael A. PfallerAbstract:In this chapter, we review the available published data addressing the clinical relevance of Antifungal Susceptibility test results. By far the most data exist to support the clinical relevance of AFST results for Candida against fluconazole, and these data suggest that the clinical utility of this information mirrors that put forward for antibacterial Susceptibility testing. Clinical relevance has also been demonstrated for selected other Antifungal agents against Candida and Cryptococcus spp. By contrast, little direct support for the clinical utility of AFST for moulds is available.
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Antifungal Susceptibility testing methods.
Current Drug Targets, 2005Co-Authors: Michael A. PfallerAbstract:: The number of systemically active Antifungal agents has increased dramatically in recent years in response to the challenge of invasive mycoses. Additional work is needed to better understand the mechanisms of action of these agents as well as the mechanisms of resistance expressed by the fungal pathogens. Antifungal Susceptibility testing has been standardized and refined and now may be considered to play an important role in the management of invasive mycoses. More work is needed to optimize the methods for testing new Antifungal agents and for testing pathogens other than Candida. The ongoing efforts and international collaborations designed to address these issues will provide important information that will improve the management of serious fungal infections.
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has Antifungal Susceptibility testing come of age
Clinical Infectious Diseases, 2002Co-Authors: Michael A. PfallerAbstract:: The in vitro Susceptibility of an infecting organism to the antimicrobial agent selected for therapy is one of several factors that influence the likelihood that therapy for an infection will be successful. To appreciate the value of Antifungal Susceptibility testing, it is helpful to review the overall predictive utility of antibacterial Susceptibility testing. After >30 years of study, in vitro Susceptibility can be said to predict the response of bacterial infections with an accuracy that is well summarized as the "90-60 rule": infections due to susceptible isolates respond to therapy approximately 90% of the time, whereas infections due to resistant isolates respond approximately 60% of the time. On the basis of a growing body of knowledge, standardized Susceptibility testing for selected organism-drug combinations (most notably, Candida species and the azole Antifungal agents) has been shown to have similar predictive utility. Antifungal Susceptibility testing is now increasingly and appropriately used as a routine adjunct to the treatment of fungal infections.
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Antifungal Susceptibility testing. New technology and clinical applications.
Infectious Disease Clinics of North America, 2001Co-Authors: Michael A. Pfaller, Wen Liang YuAbstract:: The state of the art for Susceptibility testing of yeasts is comparable with that of bacteria. Standardized methods for performing Antifungal Susceptibility testing are reproducible, accurate, and available in clinical laboratories. The development of quality control limits and interpretive criteria for a limited number of Antifungal agents provides a basis for the application of this testing in the clinical laboratory. A proficiency testing program is available as a quality assurance measure for laboratories and has documented steady improvement among laboratories using the NCCLS method. As with antibacterial agents, surveillance programs are now in place using reference quality testing methods to monitor Antifungal resistance trends on a global scale. It is clear that Antifungal Susceptibility testing can predict outcome in several clinical situations. Susceptibility testing is most helpful in dealing with infection caused by non-albicans species of Candida, and Susceptibility testing of azoles is increasingly important in the management of candidiasis in critically ill patients. Susceptibility testing also has been standardized for filamentous fungi that cause invasive infections. Studies are ongoing to further refine this approach and evaluate the in vivo correlation with the in vitro data for molds. Future efforts must be directed toward establishing and validating interpretive break-points for licensed Antifungals such as amphotericin B, and for new Antifungals that are not yet licensed. Finally, procedures must be optimized for testing non-Candida yeasts (e.g., C. neoformans) and molds.
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In vitro Antifungal Susceptibility testing.
Pharmacotherapy, 2001Co-Authors: Holly L. Hoffman, Michael A. PfallerAbstract:With the rising frequency of fungal infections, as well as increasing reports of resistance to Antifungal agents, it is imperative that clinically applicable Antifungal Susceptibility testing be available. In 1997 the National Committee for Clinical Laboratory Standards published standard guidelines for Antifungal Susceptibility testing of Candida sp and Cryptococcus neoformans with amphotericin B, flucytosine, fluconazole, itraconazole, and ketoconazole. Although the methods are standard, they are time consuming, can be difficult to interpret, and are approved only for testing limited organisms and drugs. Modifications to the methods and alternative approaches have been proposed to make these tests more convenient and efficient, applicable to a greater number of species, and appropriate for performing in the clinical laboratory.
Jacques F. Meis - One of the best experts on this subject based on the ideXlab platform.
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Antifungal Susceptibility Testing of Fusarium: A Practical Approach.
Journal of Fungi, 2017Co-Authors: Abdullah M. S. Al-hatmi, Jacques F. Meis, Ilse Curfs-breuker, G. Sybren De Hoog, Paul E. VerweijAbstract:In vitro Susceptibility testing of Fusarium is becoming increasingly important because of frequency and diversity of infections and because resistance profiles are species-specific. Reference methods for Antifungal Susceptibility testing (AFST) are those of Clinical and Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility (EUCAST), but breakpoints (BPs) have not yet been established. One of the problems is that phylogenetic distances between Fusarium species are much smaller than between species of, e.g., Candida. Epidemiological cutoff values (ECVs) for some Fusarium species have been determined in order to differentiate wild-type from non-wild-type isolates. In clinical routine, commercially available assays such as Etest, Sensititre or others provide essential agreement with reference methods. Our objective is to summarize Antifungal Susceptibility testing of Fusarium genus in the clinical laboratory: how to do it, when to do it, and how to interpret it.
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Molecular epidemiology and Antifungal Susceptibility of Serbian Cryptococcus neoformans isolates
Mycoses, 2014Co-Authors: Valentina Arsic Arsenijevic, Marina Pekmezovic, Jacques F. Meis, Ferry HagenAbstract:Molecular typing and Antifungal Susceptibility testing of 34 clinical Serbian Cryptococcus neoformans isolates from 25 patients was retrospectively performed. Amplified fragment length polymorphism (AFLP) fingerprinting was used for genotyping, whereas a novel real-time PCR was used to determine the mating- and serotype. The Antifungals amphotericin B, 5-fluorocytosine, fluconazole, voriconazole, itraconazole and posaconazole were used to determine the Antifungal Susceptibility profiles. The majority of isolates belonged to genotype AFLP1/VNI (n = 20; 58.8%), followed by AFLP2/VNIV (n = 10; 29.4%), AFLP3/VNIII (n = 3; 8.8%) and AFLP1B/VNII (n = 1; 2.9%). All AFLP1/VNI isolates were mating-serotype alphaA, the sole AFLP1B/VNII isolate was found to be aA, whereas AFLP2/VNIV harboured serotype D isolates with either the a (n = 2; 5.9%) or alpha (n = 8; 23.5%) mating-type allele. The isolates (n = 3; 8.8%) that were found to be genotype AFLP3/VNIII had the hybrid mating- and serotype combination aA-alphaD. In vitro Antifungal Susceptibility testing showed that all isolates were susceptible to amphotericin B, voriconazole and posaconazole. Low resistance level was observed for fluconazole (n = 1; 2.9%) and 5-fluorocytosine. (n = 2; 5.8%). A large percentage of isolates was found to be susceptible dose dependent to itraconazole (n = 16; 47.1%). AFLP1/VNI was the most common genotype among clinical C. neoformans isolates from immunocompromised patients in Serbia. C. neoformans from HIV-negative patients were significantly less susceptible to 5-fluorocytosine (P < 0.01). Correlation between genotypes and Antifungal Susceptibility was not observed.
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taxonomy and Antifungal Susceptibility of clinically important rasamsonia species
Journal of Clinical Microbiology, 2013Co-Authors: Jos Houbraken, Jacques F. Meis, Sandrine Giraud, M Meijer, Sebastien Bertout, Jens Christian Frisvad, Jeanphilippe Bouchara, R A SamsonAbstract:In recent years, Geosmithia argillacea has been increasingly reported in humans and animals and can be considered an emerging pathogen. The taxonomy of Geosmithia was recently studied, and Geosmithia argillacea and related species were transferred to the new genus Rasamsonia. The diversity among a set of Rasamsonia argillacea strains, including 28 clinical strains, was studied, and Antifungal Susceptibility profiles were generated. Data obtained from morphological studies and from phylogenetic analyses of internal transcribed spacer (ITS) and partial β-tubulin and calmodulin sequences revealed the presence of four species in the Rasamsonia argillacea complex, two of which are newly described here: R. piperina sp. nov. and R. aegroticola sp. nov. In contrast to other related genera, all Rasamsonia species can be identified with ITS sequences. A retrospective identification was performed on recently reported clinical isolates from animal or human patients. Susceptibility tests showed that the Antifungal Susceptibility profiles of the four members of the R. argillacea complex are similar, and caspofungin showed significant activity in vitro, followed by amphotericin B and posaconazole. Voriconazole was the least active of the Antifungals tested. The phenotypically similar species R. brevistipitata and R. cylindrospora had different Antifungal Susceptibility profiles, and this indicates that correct species identification is important to help guide appropriate Antifungal therapy.
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species specific Antifungal Susceptibility patterns of scedosporium and pseudallescheria species
Antimicrobial Agents and Chemotherapy, 2012Co-Authors: Michaela Lackner, Paul E. Verweij, Sybren G De Hoog, Mohammad Javad Najafzadeh, Ilse Curfsbreuker, Corne H W Klaassen, Jacques F. MeisAbstract:Since the separation of Pseudallescheria boydii and P. apiosperma in 2010, limited data on species-specific Susceptibility patterns of these and other species of Pseudallescheria and its anamorph Scedosporium have been reported. This study presents the Antifungal Susceptibility patterns of members affiliated with both entities. Clinical and environmental isolates (n = 332) from a wide range of sources and origins were identified down to species level and tested according to CLSI M38-A2 against eight Antifungal compounds. Whereas P. apiosperma (geometric mean MIC/minimal effective concentration [MEC] values of 0.9, 2.4, 7.4, 16.2, 0.2, 0.8, 1.5, and 6.8 μg/ml for voriconazole, posaconazole, isavuconazole, itraconazole, micafungin, anidulafungin, caspofungin, and amphotericin B, respectively) and P. boydii (geometric mean MIC/MEC values of 0.7, 1.3, 5.7, 13.8, 0.5, 1.4, 2.3, and 11.8 μg/ml for voriconazole, posaconazole, isavuconazole, itraconazole, micafungin, anidulafungin, caspofungin, and amphotericin B, respectively) had similar Susceptibility patterns, those for S. aurantiacum, S. prolificans, and S. dehoogii were different from each other. Voriconazole was the only drug with significant activity against S. aurantiacum isolates. The MIC distributions of all drugs except voriconazole did not show a normal distribution and often showed two subpopulations, making a species-based prediction of Antifungal Susceptibility difficult. Therefore, Antifungal Susceptibility testing of all clinical isolates remains essential for targeted Antifungal therapy. Voriconazole was the only compound with low MIC values (MIC90 of ≤2 μg/ml) for P. apiosperma and P. boydii. Micafungin and posaconazole showed moderate activity against the majority of Scedosporium strains.
Michael G. Rinaldi - One of the best experts on this subject based on the ideXlab platform.
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Antifungal Susceptibility testing of exophiala spp a head to head comparison of amphotericin b itraconazole posaconazole and voriconazole
Medical Mycology, 2009Co-Authors: Annette W. Fothergill, Michael G. Rinaldi, Deanna A. SuttonAbstract:Frequently, diseases caused by black yeasts are chronic in nature with a high morbidity. In addition, these infections are often fatal and relapse is common, even after prolonged treatment. Although the CLSI Document M38-A outlines methods for Antifungal Susceptibility testing of moulds, Exophiala spp. are not directly discussed. In an effort to determine the Antifungal Susceptibility patterns of Exophiala spp. we tested 160 clinical isolates against amphotericin B, itraconazole, posaconazole, and voriconazole in a head-to-head comparison. Posaconazole and itraconazole were the most active in vitro with MICs falling well below the achievable serum levels typically observed with standard dosing regimens.
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Antifungal Susceptibility testing.
Infectious Disease Clinics of North America, 2006Co-Authors: Annette W. Fothergill, Michael G. Rinaldi, Deanna A. SuttonAbstract:: Antifungal Susceptibility testing has been in routine use now for more than 15 years and has become a useful tool for clinicians who are faced with difficult treatment decision. Although most clinicians order Susceptibility testing, much confusion still exists regarding the use of the results. Sufficient data have been generated to determine Susceptibility trends for specific fungi against specific agents, but correlation data are minimal. Despite the lack of correlation data, Antifungal Susceptibility testing continues to provide useful information to assist with patient care.
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Antifungal Susceptibility testing technical advances and potential clinical applications
Clinical Infectious Diseases, 1997Co-Authors: Michael A. Pfaller, Michael G. RinaldiAbstract:: The clinical application of in vitro Antifungal Susceptibility testing has been limited by a lack of reproducibility and uncertain clinical relevance. As a result of several collaborative studies, the National Committee for Clinical Laboratory Standards (NCCLS) has proposed a standardized Antifungal Susceptibility test method, NCCLS M27-T. More convenient, user-friendly methods (microdilution broth and stable gradient technology) have been evaluated, and the potential for a similar process with a disk diffusion method is apparent. Adaptation of the standard method for Susceptibility testing of filamentous fungi appears promising. The existence of a standardized method facilitates meaningful analysis of studies addressing the issue of clinical relevance of Antifungal Susceptibility testing. Correlation of MICs with clinical response to therapy is beginning to emerge, most notably in relation to fluconazole and itraconazole therapy for oropharyngeal candidiasis associated with infection with the human immunodeficiency virus. This accumulated experience with Antifungal Susceptibility testing allows us to provide several specific recommendations for Antifungal Susceptibility testing in the clinical laboratory. Application of this developing technology to new Antifungal agents and other disease states will enhance our ability to effectively deal with the emerging problem of fungal infection.
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Antifungal Susceptibility testing
Clinical Microbiology Reviews, 1993Co-Authors: Michael A. Pfaller, Michael G. Rinaldi, Anamarie Polak, John N GalgianiAbstract:Unlike antibacterial Susceptibility testing, reliable Antifungal Susceptibility testing is still largely in its infancy. Many methods have been described, but they produce widely discrepant results unless such factors as pH, inoculum size, medium formulation, incubation time, and incubation temperature are carefully controlled. Even when laboratories agree upon a common method, interlaboratory agreement may be poor. As a result of numerous collaborative projects carried out both independently and under the aegis of the Subcommittee on Antifungal Susceptibility Testing of the National Committee for Clinical Laboratory Standards, the effects of varying these factors have been extensively studied and a standard method which minimizes interlaboratory variability during the testing of Candida spp. and Cryptococcus neoformans has been proposed. This review summarizes this work, reviews the strengths and weaknesses of the proposed Susceptibility testing standard, and identifies directions for future work.
R A Samson - One of the best experts on this subject based on the ideXlab platform.
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taxonomy and Antifungal Susceptibility of clinically important rasamsonia species
Journal of Clinical Microbiology, 2013Co-Authors: Jos Houbraken, Jacques F. Meis, Sandrine Giraud, M Meijer, Sebastien Bertout, Jens Christian Frisvad, Jeanphilippe Bouchara, R A SamsonAbstract:In recent years, Geosmithia argillacea has been increasingly reported in humans and animals and can be considered an emerging pathogen. The taxonomy of Geosmithia was recently studied, and Geosmithia argillacea and related species were transferred to the new genus Rasamsonia. The diversity among a set of Rasamsonia argillacea strains, including 28 clinical strains, was studied, and Antifungal Susceptibility profiles were generated. Data obtained from morphological studies and from phylogenetic analyses of internal transcribed spacer (ITS) and partial β-tubulin and calmodulin sequences revealed the presence of four species in the Rasamsonia argillacea complex, two of which are newly described here: R. piperina sp. nov. and R. aegroticola sp. nov. In contrast to other related genera, all Rasamsonia species can be identified with ITS sequences. A retrospective identification was performed on recently reported clinical isolates from animal or human patients. Susceptibility tests showed that the Antifungal Susceptibility profiles of the four members of the R. argillacea complex are similar, and caspofungin showed significant activity in vitro, followed by amphotericin B and posaconazole. Voriconazole was the least active of the Antifungals tested. The phenotypically similar species R. brevistipitata and R. cylindrospora had different Antifungal Susceptibility profiles, and this indicates that correct species identification is important to help guide appropriate Antifungal therapy.
Jose L Lopezribot - One of the best experts on this subject based on the ideXlab platform.
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standardized method for in vitro Antifungal Susceptibility testing of candida albicans biofilms
Antimicrobial Agents and Chemotherapy, 2001Co-Authors: Gordon Ramage, Vande K Walle, Brian L Wickes, Jose L LopezribotAbstract:Candida albicans is implicated in many biomaterial-related infections. Typically, these infections are associated with biofilm formation. Cells in biofilms display phenotypic traits that are dramatically different from those of their free-floating planktonic counterparts and are notoriously resistant to antimicrobial agents. Consequently, biofilm-related infections are inherently difficult to treat and to fully eradicate with normal treatment regimens. Here, we report a rapid and highly reproducible microtiter-based colorimetric assay for the Susceptibility testing of fungal biofilms, based on the measurement of metabolic activities of the sessile cells by using a formazan salt reduction assay. The assay was used for in vitro Antifungal Susceptibility testing of several C. albicans strains grown as biofilms against amphotericin B and fluconazole and the increased resistance of C. albicans biofilms against these Antifungal agents was demonstrated. Because of its simplicity, compatibility with a widely available 96-well microplate platform, high throughput, and automation potential, we believe this assay represents a promising tool for the standardization of in vitro Antifungal Susceptibility testing of fungal biofilms.
