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DRUG-SENSITIVE TB (DSTB) AND DRUG-RESISTANT TB (DRTB): COMPREHENSIVE ANSWER (15 Marks)

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PART A: DRUG-SENSITIVE TUBERCULOSIS (DSTB)

Definition

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Classification of Anti-TB Drugs

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Standard Treatment Regimen for New DS-TB Patients

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Drug Doses (Daily; adults)

In TB meningitis: replace Ethambutol with Streptomycin.

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Principles of Treatment

• Regimens must contain a combination of drugs (to prevent emergence of resistance)
• IP eliminates large rapidly-multiplying bacillary populations; prevents early death
• CP targets semi-dormant persister organisms with sterilising drugs; prevents relapse
• Thrice-weekly intermittent treatment has been discontinued; daily therapy is recommended
• Universal DST is now mandatory before assigning treatment regimen
• Treatment must be registered on Nikshay portal (PMDT 2021, Slide 48)

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Follow-up in DS-TB

• Sputum smear/culture at end of IP, and if positive during CP
• If smear-positive during CP → send for rapid molecular DST / culture-DST for R and H resistance (Sharma & Mohan, Ch. 44)

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PART B: DRUG-RESISTANT TUBERCULOSIS (DRTB)

Definitions and Classification (PMDT 2021, Slide 9)

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Causes of DR-TB (PMDT 2021, Slide 5)

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Diagnosis of DR-TB

1. NAAT (CBNAAT/Truenat): Detects MTB + RR-TB simultaneously; point-of-care
2. Xpert MTB/XDR: Follow-on test; detects resistance to H, FQ, SLI and Eto
3. Line Probe Assay (LPA):
   • FL-LPA: detects resistance to R, H (katG + inhA mutations)
   • SL-LPA: detects resistance to FQ and SLI
4. Liquid Culture (MGIT 960): DST for first-line and second-line drugs; monitors treatment response (PMDT 2025, Slide 3)

• All presumptive TB → NAAT → if RR detected: FL-LPA + SL-LPA + LC-DST
• If RR not detected: FL-LPA for H resistance
• Results entered into Nikshay portal same day

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Drug Grouping for DR-TB Treatment (PMDT 2021, Slide 36; WHO 2020)

Kanamycin and Capreomycin are no longer recommended (associated with poorer outcomes).

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Treatment Regimens for DR-TB (PMDT 2025, Slides 7–27; PMDT 2021)

1. H Mono/Poly DR-TB Regimen

• Regimen: Lfx + R + Z + E (6–9 months, no IP/CP separation)
• Duration: Standard 6 months; extended to 9 months if: extensive disease, uncontrolled comorbidity, EP-TB, or smear positive at end of month 4
• Replacement: If Lfx can't be used → Mfxh; if Z can't be used → Lzd; if both Mfx+Z can't be used → add 2 of: Lzd, Cfz, Cs

2. BPaLM Regimen (6–9 months) — Priority regimen for MDR/RR-TB (PMDT 2025)

• Age ≥14 years
• New microbiologically confirmed RR-TB
• QTcF ≤450 ms (male), ≤470 ms (female)
• No prior treatment with Bdq, Lzd, Pa for >1 month (unless sensitivity documented)

• Age <14 years
• Documented resistance to Bdq, Lzd or Pa
• Significant liver dysfunction (LFT >3× ULN)
• Severe EP-TB (CNS TB, spinal/skeletal, disseminated TB)
• Pregnant or lactating women
• Significant cardiac abnormalities / Long QT syndrome
• Hb <8 g/dL (not rapidly correctable), severe neutropenia (<750/mm³) or thrombocytopenia (<100,000/mm³)

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3. Shorter Oral MDR/RR-TB Regimen (9–11 months)

• Eligibility: RR-TB ± H resistance (katG or inhA, NOT both), FQ resistance not detected, no extensive disease, no severe EP-TB
• Regimens (options):
  • A: (2) Lzd + (4–6) Lfx + Cfz + Z + E + Hh / (6–9) Bdq + (5) Lfx + Cfz + Z + E
  • B: (4–6) Lfx + Cfz + Eto + Z + E + Hh / (6–9) Bdq + (5) Lfx + Cfz + Z + E (if Lzd intolerant/resistant)

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4. Longer Oral M/XDR-TB Regimen (18–20 months)

• Individualized based on DST
• Start with all 3 Group A agents + ≥1 Group B agent (minimum 4 effective drugs)
• Continue with 4 drugs beyond 6–9 months; if only 1–2 Group A agents usable → both Group B agents must be included
• Regimen: (6–9m) Bdq + (18–20m) Lfx + Lzd + Cfz + Cs

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Pre-Treatment Evaluation (PTE) for DR-TB (PMDT 2025, Slide 10)

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Follow-Up Monitoring — BPaLM Regimen (PMDT 2025, Slides 15–16)

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Special Situations

Pregnancy and Lactation (PMDT 2025, Slides 19–20)

• BPaLM is contraindicated in pregnancy/lactation
• SLIs contraindicated (8th cranial nerve toxicity to foetus)
• Eto contraindicated before 32 weeks (teratogenic)
• Recommended: 9-month shorter oral MDR/RR-TB regimen with Lzd
• If gestation >20 weeks and patient unwilling for MTP → 9-month shorter or longer oral regimen

Children (PMDT 2025, Slide 21)

• BPaLM (with Pa): safety not established for <14 years
• Children <14 years → 9–11 month shorter or 18–20 month longer oral regimen
• Children <5 years: Bdq not available → replaced by Am/Km (shorter) or Dlm (longer)

PLHIV (PMDT 2025, Slide 22)

• BPaLM can be given regardless of HIV status/CD4 count (if other criteria met)
• Avoid Efavirenz (reduces Bdq and Pa exposure)
• Use Dolutegravir (DTG) with BPaLM
• Avoid Zidovudine with Lzd (myelosuppression cross-toxicity)

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Treatment Outcomes (Definitions)

• Cured: Smear/culture negative at end of treatment + at least one previous negative
• Treatment Failed: Smear/culture positive at month 5 or later (or earlier decision based on clinical deterioration)
• Lost to follow-up, Not evaluated, Treatment success as per standard definitions

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Key Points to Remember

1. Universal DST must precede treatment assignment
2. All patients registered on Nikshay; never batch specimens — transport immediately
3. Supervised therapy (≥85% doses supervised) is critical for BPaLM
4. Monitoring turnaround time improves outcomes
5. Long-term follow-up for 2 years after completing any DR-TB regimen
6. Post-treatment 6-monthly follow-up must be performed strictly for 2 years in every DR-TB patient

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