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ISONIAZID (H) MONO-RESISTANT & POLY DRUG-RESISTANT TB (H Mono/Poly DR-TB)

(PMDT Guidelines 2021 & March 2025 | 15-Mark MD Exam Answer)

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1. DEFINITIONS

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2. WHEN TO SUSPECT / DIAGNOSIS

• FL-LPA (First-Line Line Probe Assay) detects H resistance in a patient with RIF resistance NOT detected on NAAT (CBNAAT/Truenat)
• FL-LPA serves as a surrogate of first-line poly resistance as per NDRS

• NAAT → RR not detected → offer FL-LPA for H resistance
• If H resistance detected → eligible for H mono/Poly DR-TB regimen
• Simultaneously: SL-LPA for FQ resistance; LC-DST for Mfx (if resistant by SL-LPA), Z, Lzd, Cfz* ( when available)*
• Treatment initiated based on LPA results; modified later based on LC-DST results

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3. TREATMENT ALGORITHM — H MONO/POLY DR-TB

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4. PRE-TREATMENT EVALUATION (PTE)

• PTE valid for 1 month from date of test result
• aDSM (Active Drug Safety Management & Monitoring) initiation form must be completed for all DR-TB patients at start of each new episode

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5. REGIMEN

• 6(H)REZ has higher treatment success than >6(H)REZ
• Addition of fluoroquinolone to (H)REZ improves treatment success (aOR 2.8; 95% CI 1.1–7.3)
• Addition of FQ also reduces deaths (aOR 0.4) and acquisition of MDR-TB (aOR 0.10)

Important: Empirical treatment of H mono/poly DR-TB is NOT advised. R resistance must be excluded by NAAT before starting this regimen.

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6. DOSAGES

In exceptional situations of unavailability of loose drug R or E or Z, the use of 4-FDC (HREZ) with Lfx loose tablets may be considered as an option rather than not starting the patient on treatment. (Slide 51)

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7. DURATION & TREATMENT EXTENSION

• Standard total duration: 6 months
• Extended directly to 9 months (no monthly increments) in:
  1. Extensive disease
  2. Uncontrolled comorbidity
  3. Extra-pulmonary TB
  4. Smear positive at end of Month 4
  5. When regimen is modified
• Treatment Failure: If sputum smear remains positive at end of Month 5 or later → declare "treatment failed" → re-evaluate as non-responder per diagnostic algorithm

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8. REPLACEMENT SEQUENCE (Slide 54, PMDT 2021 | Slide 27, PMDT 2025)

1. Additional resistance detected
2. Adverse drug reactions / intolerance
3. Non-availability of any drug
4. Contraindication / emergence of exclusion criteria

When the resistance to Z or FQ (or both) is detected, or intolerance / non-availability occurs, use the replacement sequence as below:

• Any drug in the H mono/poly DR-TB regimen can be replaced/modified
• Re-initiation or re-registration is NOT required if regimen change occurs during initial 4 months (same registration date continues), unless patient is declared 'treatment failed'

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9. FOLLOW-UP MONITORING

A. Bacteriological Monitoring

• Final treatment outcome declared on culture results
• Long-term follow-up: 6-monthly cultures in symptomatic patients up to 2 years post-treatment (months 6, 12, 18, 24)

B. Weight Band Monitoring

• Adults: if weight changes by ≥5 kg and crosses weight band → change weight band at next month's box
• Children: drug dosage adjusted immediately when weight crosses weight-band range

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10. SPECIAL SITUATIONS

A. Children (Slide 59)

• Management same as adults
• Child-friendly formulations to be used

B. Pregnancy & Lactation (Slide 60)

• H mono/poly DR-TB regimen may be started or continued in pregnant women
• Rifampicin interacts with OCP → reduced contraceptive efficacy
  • Use OCP with 50 μg estrogen, or
  • Barrier methods (condoms/diaphragms), IUD (CuT), or Depo-Provera

C. PLHIV (Slide 62)

• H mono/poly DR-TB regimen recommended in HIV-reactive patients
• ART to be started within 8 weeks of TB treatment initiation (regardless of CD4 count)

D. Extra-pulmonary TB (Slide 63)

• Treatment designed in consultation with specialists (infectious disease, neurologists)
• In CNS, skeletal, miliary TB → treatment may be given up to 1 year

E. Extensive disease (Slide 61)

• Prolongation up to maximum 12 months may be considered on individual basis

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11. ADVERSE DRUG REACTIONS (Slide 64)

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12. KEY POINTS TO REMEMBER (Slide 65, PMDT 2021)

1. H mono/poly DR-TB regimen is initiated when RIF resistance is NOT detected and H resistance IS detected
2. Started at peripheral health facility level after PTE
3. Regimen: 6 (or 9) months — Lfx R E Z
4. Replacement as per replacement sequence when additional resistance, ADR, non-availability, or contraindication occurs
5. Same regimen for children, PLHIV, and pregnant women; longer regimen for EPTB
6. Follow-up: clinically monthly; smear monthly from month 3; culture at months 3, 6, (9)
7. Failure declared if smear/culture positive at month 5 or later
8. Treatment outcome declared based on culture results

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13. UPDATED GUIDANCE — PMDT MARCH 2025

• Regimen remains: Lfx R Z E × 6–9 months
• When patient not responding / failing H mono/poly DR-TB regimen:
  • If R resistance develops → consider BPaLM / shorter MDR/RR-TB regimen as per eligibility
  • If resistance to FQ/Z or both develops → use replacement sequence
  • Patients failing with R, FQ, or Z resistance → labelled 'probable MDR-TB case' → evaluate in preferred order:
    1. BPaLM (if eligible)
    2. 9-month shorter oral MDR/RR-TB regimen (if eligible)
    3. Longer oral M/XDR-TB regimen

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SUMMARY TABLE

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