Lab Medicine Significance 7/10

Resolving Genotype-Phenotype Discordance in Rapid Molecular AST Panels

Syndromic molecular panels can identify organisms and resistance genes directly from positive blood cultures within hours, but discrepancies with subsequent phenotypic AST create interpretive challenges. This review provides stepwise approaches for clinical laboratories to resolve discordant genotypic and phenotypic susceptibility results, addressing a critical practical gap as molecular diagnostics become standard in clinical microbiology workflows.

The original study

The Genotype-to-Phenotype Dilemma: How Should Laboratories Approach Discordant Susceptibility Results?

Authors
Yee R, Dien Bard J, Simner PJ
Journal
Journal of clinical microbiology
Type
Journal Article, Review
PMID
33441396
Read the original study →

Original abstract

Traditional culture-based methods for identification and antimicrobial susceptibility testing (AST) of bacteria take 2 to 3 days on average. Syndromic molecular diagnostic panels have revolutionized clinical microbiology laboratories as they can simultaneously identify an organism and detect some of the most significant antimicrobial resistance (AMR) genes directly from positive blood culture broth or from various specimen types (e.g., whole blood, cerebrospinal fluid, and respiratory specimens). The presence or absence of an AMR marker associated with a particular organism can be used to predict the phenotypic AST results to more rapidly guide therapy. Numerous studies have shown that genotypic susceptibility predictions by syndromic panels can improve patient outcomes. However, an important limitation of AMR marker detection to predict phenotype is the potential discrepancies that may arise upon performing phenotypic AST of the recovered organism in culture. The focus of this minireview is to address how clinical laboratories should interpret rapid molecular results from commercial platforms in relation to phenotypic AST. Stepwise approaches and solutions are provided to resolve discordant results between genotypic and phenotypic susceptibility results.