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

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.

Keywords: antimicrobial resistance; antimicrobial susceptibility testing; molecular methods; predictions.

FIG 1

Workflow for resolving discrepant genotypic and phenotypic susceptibility results.

FIG 2

Potential steps and reporting structure for specific discrepant examples found in Gram-positive organisms (e.g., Enterococcus species and Staphylococcus aureus). Abbreviations: R, resistant (described as having the potential to be both resistant and intermediate resistant); NAAT, nucleic acid amplification test.

FIG 3

Potential steps and reporting structure for specific discrepant examples found in Gram-negative organisms (e.g., Enterobacterales). Abbreviations: R, resistant (described as having the potential to be both resistant and intermediate resistant); NAAT, nucleic acid amplification test; ESBL, extended-spectrum beta-lactamase; 3GC, third-generation cephalosporins; 4GC, fourth-generation cephalosporins; AMR, antimicrobial resistance; AST, antimicrobial susceptibility testing.