What this test measures
This test determines whether a cultured M. tuberculosis isolate is sensitive or resistant to isoniazid (INH, H) at the WHO-defined critical concentration. Isoniazid blocks mycolic acid synthesis via the inhA pathway after activation by the bacterial katG enzyme. Resistance is most often due to katG S315T (high-level resistance) or inhA promoter mutations (low-level resistance, with ethionamide cross-resistance).
Phenotypic DST on MGIT or LJ is the reference standard. Molecular tests (CBNAAT for rifampicin; LPA for isoniazid + rifampicin) provide rapid screening for the most common mutations.
Why it matters
Isoniazid mono-resistance (resistant to H, sensitive to R) is increasingly common in India — affecting close to 1 in 10 newly diagnosed TB cases according to national drug-resistance surveys. WHO and NTEP recommend a modified 6-month regimen (RZE + Levofloxacin) for confirmed H-mono-resistance, instead of the standard HRZE → HR. Detecting H resistance early therefore prevents treatment failure and resistance amplification.
Isoniazid is also widely used in TB preventive treatment (TPT) for contacts and HIV-positive individuals; resistance has implications for TPT regimen choice as well.
How to prepare
A positive M. tuberculosis culture (MGIT or LJ) is required. If not yet available, sputum samples must be collected for AFB culture first. Tell the lab if any LPA result is available (katG / inhA status) — it helps interpret discrepancies.
Markers & reference ranges
Reference ranges below are typical adult values. Your lab's reported range may differ slightly based on the assay platform and patient demographics — always read your report against the range printed on it.
| Marker | Normal range | If low | If high |
|---|---|---|---|
| Isoniazid (—)[1][2] | Sensitive | — | Resistant — isoniazid should not be used. Distinguish high-level (katG S315T) from low-level (inhA promoter) resistance if possible — the latter implies ethionamide cross-resistance. WHO H-mono-resistance regimen (6 RZE-Lfx) applies if rifampicin is sensitive. |
Isoniazid resistance mechanisms
| Mutation | Resistance level | Cross-resistance |
|---|---|---|
| katG S315T | High-level | No cross-resistance with ethionamide |
| inhA promoter | Low-level | Ethionamide cross-resistant |
| Other katG mutations | Variable | Variable |
Frequently asked questions
How common is isoniazid resistance in India?
Isoniazid mono-resistance affects about 1 in 10 new TB cases according to India's drug resistance survey. It is one of the most common drug-resistance patterns in the country.
What is the regimen for H mono-resistance?
WHO recommends 6 months of rifampicin + pyrazinamide + ethambutol + levofloxacin (RZE-Lfx) instead of the standard HRZE → HR.
Why distinguish katG from inhA mutations?
katG mutations cause high-level isoniazid resistance and do not affect ethionamide. inhA promoter mutations cause low-level isoniazid resistance and confer ethionamide cross-resistance — important when designing a regimen.
How is this test different from LPA?
LPA is a fast molecular test that detects the common katG and inhA mutations within 1–2 days. Phenotypic DST (this test) takes longer but is the reference standard and detects resistance from mutations the LPA does not cover.
How long does the test take?
About 1–2 weeks from a positive culture; 4–6 weeks total from sputum collection.
Is the test available under NTEP?
Yes — first-line DST is provided at NTEP intermediate and national reference labs. Private NABL-accredited labs also offer it.
What about TB preventive treatment if I am an H-resistant contact?
For contacts of H-mono-resistant index cases, your TB specialist will tailor the preventive regimen — usually with rifapentine + isoniazid (HP) is avoided in favour of rifampicin or rifapentine-based options.
Related Tuberculosis / Mycobacterial tests
Tests commonly ordered alongside ANTIBIOGRAM - MTB (ISONIAZID), or that help interpret an unexpected result.
Sources & references
- WHO Consolidated Guidelines on Drug-Resistant TB · accessed 2026-05-30T00:00:00.000Z
- NTEP PMDT Guidelines · accessed 2026-05-30T00:00:00.000Z
- CDC — TB Laboratory Diagnostics · accessed 2026-05-30T00:00:00.000Z
- India TB Report 2024 · accessed 2026-05-30T00:00:00.000Z
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