title: 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.
authors.affiliation: Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, P. R. China; Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, P. R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, P. R. China; Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, P. R. China.
authors.forename: He
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, P. R. China.
authors.forename: Meng
authors.initials: M
authors.lastname: Xiao
authors.affiliation: Centre for Infectious Diseases and Microbiology Laboratory Services, Westmead Hospital, Darcy Road, Westmead, New South Wales 2145, Australia.
authors.forename: Timothy
authors.initials: T
authors.lastname: Kudinha
authors.affiliation: Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, P. R. China.
authors.forename: Lei-Li
authors.initials: LL
authors.lastname: Mao
authors.affiliation: Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, P. R. China.
authors.forename: Hao-Ran
authors.initials: HR
authors.lastname: Zhao
authors.affiliation: Centre for Infectious Diseases and Microbiology Laboratory Services, Westmead Hospital, Darcy Road, Westmead, New South Wales 2145, Australia.
authors.forename: Fanrong
authors.initials: F
authors.lastname: Kong
authors.affiliation: Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, P. R. China.
authors.forename: Ying-Chun
authors.initials: YC
authors.lastname: Xu
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D001393:Azoles / Q000737:chemistry*; D002175:Candida / Q000187:drug effects* / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests / Q000379:methods*; D011786:Quality Control; D012680:Sensitivity and Specificity; D054928:Validation Studies as Topic
chemical_list: D000935:Antifungal Agents; D001393:Azoles