Microbiology · Mycobacterial and Fungal Diagnostics (NAAT, LPA, Culture, DST, IGRA, Galactomannan)

In phenotypic drug susceptibility testing (DST) for M. tuberculosis on Lowenstein-Jensen medium, isoniazid resistance is tested at two concentrations: 0.2 µg/mL and 1.0 µg/mL. Growth at 0.2 µg/mL but not 1.0 µg/mL indicates:

  • A High-level INH resistance (likely katG S315T mutation)
  • B Full susceptibility; the 0.2 µg/mL growth is non-specific
  • C Borderline susceptibility — no clinical relevance for treatment decisions
  • D Low-level INH resistance (likely inhA promoter mutation)
Correct answer: D. Low-level INH resistance (likely inhA promoter mutation)

Explanation

Low-level INH resistance, defined as growth at the critical concentration of 0.2 µg/mL but not at 1.0 µg/mL, is typically caused by mutations in the inhA promoter region, which reduce InhA expression and confer MICs of 0.2–1.0 µg/mL. High-level resistance (growth at both concentrations, MIC >1.0 µg/mL) is associated with katG mutations (especially S315T), which destroy catalase-peroxidase activity needed for INH activation. The distinction has treatment implications, as high-dose INH may overcome low-level resistance in some regimens.

Reference: Ananthanarayan & Paniker's Textbook of Microbiology, 11th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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