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Antifungal susceptibility testing: current role from the clinical laboratory perspective.

ABSTRACT: Despite availability of many antifungal agents, antifungal clinical resistance occurs, perhaps as a consequence of an infecting organism found to be resistant in vitro to one or more antifungals tested. From what derives the important current role of the in vitro antifungal susceptibility testing (AFST), that is to determine which agents are like to be scarcely effective for a given infection. Thus, AFST results, if timely generated by the clinical microbiology laboratory and communicated to clinicians, can aid them in the therapeutic decision making, especially for difficult-to-treat invasive candidiasis and aspergillosis. Although recently refined AFST methods are commercially available for allowing a close antifungal resistance surveillance in many clinical setting, novel assays such as flow cytometry or MALDI-TOF mass spectrometry are upcoming tools for AFST. Based on short-time antifungal drug exposure of fungal isolates, these assays could provide a reliable means for quicker and sensitive assessment of AFST.

SUBMITTER: Posteraro B

PROVIDER: S-EPMC4010604 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Antifungal susceptibility testing: current role from the clinical laboratory perspective.

Posteraro Brunella B Torelli Riccardo R De Carolis Elena E Posteraro Patrizia P Sanguinetti Maurizio M

Mediterranean journal of hematology and infectious diseases 20140407 1

Despite availability of many antifungal agents, antifungal clinical resistance occurs, perhaps as a consequence of an infecting organism found to be resistant in vitro to one or more antifungals tested. From what derives the important current role of the in vitro antifungal susceptibility testing (AFST), that is to determine which agents are like to be scarcely effective for a given infection. Thus, AFST results, if timely generated by the clinical microbiology laboratory and communicated to cli ...[more]

PMID: 24804003

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Project description:ObjectivesThe antifungal susceptibility testing (AFST) of yeast pathogen alerts clinicians about the potential emergence of resistance. In this study, we compared two commercial microdilution AFST methods: Sensititre YeastOne read visually (YO) and MICRONAUT-AM read visually (MN) or spectrophotometrically (MNV), interpreted with Clinical and Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing criteria, respectively.MethodsOverall, 97 strains from 19 yeast species were measured for nine antifungal drugs including a total of 873 observations. First, the minimal inhibitory concentration (MIC) was compared between YO and MNV, and between MNV and MN, either directly or by assigning them to five susceptibility categories. Those categories were based on the number of MIC dilutions around the breakpoint or epidemiological cut-off reference values (ECOFFs or ECVs). Second, YO and MNV methods were evaluated for their ability to detect the elevation of MICs due to mutation in antifungal resistance genes, thanks to pairs or triplets of isogenic strains isolated from a single patient along a treatment previously analyzed for antifungal resistance gene mutations. Reproducibility measurement was evaluated, thanks to three quality control (QC) strains.ResultsYO and MNV direct MIC comparisons obtained a global agreement of 67%. Performing susceptibility category comparisons, only 22% and 49% of the MICs could be assigned to categories using breakpoints and ECOFFs/ECVs, respectively, and 40% could not be assigned due to the lack of criteria in both consortia. The YO and MN susceptibility categories gave accuracies as low as 50%, revealing the difficulty to implement this method of comparison. In contrast, using the antifungal resistance gene sequences as a gold standard, we demonstrated that both methods (YO and MN) were equally able to detect the acquisition of resistance in the Candida strains, even if MN showed a global lower MIC elevation than YO. Finally, no major differences in reproducibility were observed between the three AFST methods.ConclusionThis study demonstrates the valuable use of both commercial microdilution AFST methods to detect antifungal resistance due to point mutations in antifungal resistance genes. We highlighted the difficulty to conduct conclusive analyses without antifungal gene sequence data as a gold standard. Indeed, MIC comparisons taking into account the consortia criteria of interpretation remain difficult even after the effort of harmonization.

Dataset Information

Antifungal susceptibility testing: current role from the clinical laboratory perspective.

Publications

Antifungal susceptibility testing: current role from the clinical laboratory perspective.

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