The Widely Used ATB FUNGUS 3 Automated Readings in China and Its Misleading High MICs of Candida spp. to Azoles: Challenges for Developing Countries' Clinical Microbiology Labs

Abstract

The rapid development in the clinical microbiology diagnostic assays presents more challenges for developing countries than for the developed world, especially in the area of test validation before the introduction of new tests. Here we report on the misleading high MICs of Candida spp. to azoles using the ATB FUNGUS 3 (bioMérieux, La Balme-les Grottes, France) with automated readings in China to highlight the dangers of introducing a diagnostic assay without validation. ATB FUNGUS 3 is the most commonly used commercial antifungal susceptibility testing method in China. An in-depth analysis of data showed higher levels of resistance to azoles when ATB FUNGUS 3 strips were read automatically than when read visually. Based on this finding, the performance of ATB FUNGUS 3, read both visually and automatically, was evaluated by testing 218 isolates of five clinically important Candida species, using broth microdilution (BMD) following CLSI M27-A3 as the gold-standard. The overall essential agreement (EA) between ATB visual readings and BMD was 99.1%. In contrast, the ATB automated readings showed higher discrepancies with BMD, with overall EA of 86.2%, and specifically lower EA was observed for fluconazole (80.7%), voriconazole (77.5%), and itraconazole (73.4%), which was most likely due to the trailing effect of azoles. The major errors in azole drug susceptibilities by ATB automated readings is a concern in China that can result in misleading clinical antifungal drug selection and pseudo high rates of antifungal resistance. Therefore, the ATB visual reading is generally recommended. In the meantime, we propose a practical algorithm to be followed for ATB FUNGUS 3 antifungal susceptibility for Candida spp. before the improvement in the automated reading system.

Multidrug-Resistant Candida auris Misidentified as Candida haemulonii: Characterization by Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry and DNA Sequencing and Its Antifungal Susceptibility Profile Variability by Vitek 2, CLSI Broth Microdilution, and Etest Method

“…This deviation could be attributed to the low number of isolates tested (25). Major errors of azole susceptibility in 218 isolates of 5 Candida species using another commercial automated reading system (ATB FUNGUS 3) have been reported recently from China, resulting in pseudohigh rates of antifungal resistance (26). In fact, the erroneously elevated MICs by the Vitek 2 automated reading method not only may lead to inappropriate selection of antifungal therapy but also depict false rates of high antifungal resistance in epidemiological studies.…”

Overexpression of Both ERG11 and ABC2 Genes Might Be Responsible for Itraconazole Resistance in Clinical Isolates of Candida krusei

“…Reference antifungal susceptibility testing of the study isolates was performed by ATB FUNGUS 3 according to the manufacturer’s instructions, and visually read the minimal inhibitory concentration (MIC) value [ 16 ]. There are five antigungal drugs at different concentrations: 5-flucytosine (4, 16μg/ml), amphotericin B (0.5–16μg/ml), fluconazole (1–128μg/ml), itraconazole (0.125–4μg/ml) and voriconazole (0.06–8μg/ml).…”

Strategies to Reduce Mortality in Adult and Neonatal Candidemia in Developing Countries

“…Antifungal susceptibility testing is required for the proper choice of antifungal drug. The developing countries still struggle with proper infrastructure for this facility [ 103 ]. There is a lack of country-specific guidelines in developing countries to guide the therapy, which forces them to follow the guideline of developed nations though their local epidemiology may be different from them.…”