What is a key limitation of molecular rapid diagnostics in guiding therapy?

• A. They may miss resistance mechanisms not encoded by known genes.
• B. They always perfectly predict phenotypic resistance.
• C. They are slower than culture-based AST.
• D. They do not identify organisms.

Answer: (A)

Molecular rapid diagnostics are excellent at quickly detecting organisms and certain resistance determinants by looking for known genes or mutations. Their limitation comes from being tied to what the test is designed to detect. If resistance arises through mechanisms not encoded by those known genes—such as regulatory changes that boost intrinsic resistance, novel or uncommon resistance genes not included in the panel, or non-genetic factors like altered expression or efflux that aren’t captured by the assay—the test may miss it. So even though a molecular test can rapidly guide initial therapy based on detected resistance genes, it may not perfectly predict the actual phenotypic resistance of the organism. Phenotypic susceptibility testing remains important to confirm susceptibility, especially when resistance mechanisms outside the panel are possible.