What this test measures
SIREP extends the SIRE panel by adding Pyrazinamide (Z) — a key drug in the intensive phase of TB treatment and an important one to monitor for resistance. The panel tests M. tuberculosis on culture against Streptomycin, Isoniazid, Rifampicin, Ethambutol and Pyrazinamide at WHO-defined critical concentrations.
Phenotypic pyrazinamide testing is technically challenging because the drug only works at low pH, so MGIT-based pyrazinamide DST is the most reliable phenotypic method. Many labs supplement it with molecular testing for the pncA gene, where most pyrazinamide-resistance mutations occur.
Why it matters
Pyrazinamide is a "sterilising" drug — it kills slowly metabolising bacilli that other drugs cannot, and is the reason TB treatment was shortened from 9 to 6 months. Resistance to pyrazinamide is increasingly recognised in India, particularly in MDR-TB strains, and changes the duration and choice of regimen.
For a routine drug-sensitive TB workup, SIREP gives the complete first-line picture. For MDR-TB workups, pyrazinamide DST guides whether Z can be safely included in the regimen — important because Z covers a unique metabolic niche.
How to prepare
A positive M. tuberculosis culture is required. If not yet available, sputum samples will need to be collected for AFB culture first. Inform the lab of any TB drug already taken.
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 |
|---|---|---|---|
| Streptomycin (S) (—)[1] | Sensitive | — | Resistant — streptomycin not usable. Rarely changes modern regimens because S is rarely used. |
| Isoniazid (H) (—) | Sensitive | — | Resistant — common in India. Triggers WHO's H-mono-resistance regimen (RZE + Levofloxacin) or modifies the MDR regimen as applicable. |
| Rifampicin (R) (—)[1] | Sensitive | — | Resistant — treated as MDR-TB; triggers PMDT pathway. |
| Ethambutol (E) (—) | Sensitive | — | Resistant — ethambutol not usable. Common companion to H or R resistance. |
| Pyrazinamide (Z) (—)[1] | Sensitive | — | Resistant — pyrazinamide not usable. May extend treatment duration in drug-sensitive TB or alter MDR-TB regimen choice. |
SIRE vs SIREP — what pyrazinamide adds
| Panel | Drugs tested | When to use |
|---|---|---|
| SIRE | S, H, R, E | Standard first-line workup; pyrazinamide assumed sensitive |
| SIREP (this test) | S, H, R, E, Z | Complete first-line picture; preferred when Z resistance suspected |
Frequently asked questions
Why does pyrazinamide matter?
Pyrazinamide is a sterilising drug essential to shortening TB treatment to 6 months. Resistance can extend the duration of treatment or change MDR-TB regimen choices.
How is pyrazinamide testing different from other drugs?
Pyrazinamide is only active at low pH, making phenotypic DST technically demanding. MGIT-based PZA testing is the most reliable phenotypic method; molecular pncA testing is a useful supplement.
How long does SIREP take?
About 1–3 weeks from a positive culture. Total time from sputum collection is typically 4–6 weeks.
When should I order SIREP instead of SIRE?
When you need a complete first-line picture — typical scenarios are MDR-TB workups, retreatment cases, and treatment failure investigation.
Is SIREP available under NTEP?
Yes, at NTEP intermediate and national reference labs for eligible patients. Private testing is available through NABL-accredited mycobacteriology labs.
What if SIREP shows isolated pyrazinamide resistance?
Z is removed from the regimen and replaced under specialist guidance. Treatment duration may be extended depending on other susceptibility and clinical response.
Should I do SIREP if my CBNAAT was negative for rifampicin resistance?
CBNAAT only tests rifampicin. SIREP confirms susceptibility for all five first-line drugs. Whether you need it depends on your clinical scenario and your doctor's judgment.
Related Tuberculosis / Mycobacterial tests
Tests commonly ordered alongside AFB DRUG SUSCEPTIBILITY (SIREP) 1ST LINE, 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
- India TB Report 2024 · accessed 2026-05-30T00:00:00.000Z
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