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GERICLINICS

GeriQBank · Paper II · Q5

DOTS; treatment, dose and regimens of MDR and XDR tuberculosis; drug-resistant TB

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Topic
Infection & Immunisation
Chapter
Part II — Tuberculosis
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Attempt it firstOutline your answer as a 7-mark answer before revealing it — definition, causes, evaluation, management and the geriatric angle.Reveal answer

ANSWER

Textbook Core – 6 Points

1.

Definitions of drug resistance (WHO 2021 revision). Mono-resistant — resistance to one first-line drug. Poly-resistant — resistance to more than one first-line drug other than to isoniazid and rifampicin together. MDR-TB — resistance to at least isoniazid AND rifampicin. RR-TB — rifampicin resistance with or without other resistance; managed exactly as MDR-TB. Pre-XDR-TB — MDR/RR-TB plus resistance to any fluoroquinolone. XDR-TB — MDR/RR-TB plus fluoroquinolone resistance plus resistance to at least one Group A drug (bedaquiline or linezolid).

2.

DOTS — the five components. (i) Sustained political and financial commitment; (ii) case detection by quality-assured bacteriology; (iii) standardised short-course chemotherapy given under direct observation with patient support; (iv) an uninterrupted, quality-assured drug supply and management system; and (v) standardised recording, reporting, monitoring and impact measurement. DOTS-Plus extended the framework to programmatic management of drug-resistant TB. In India, RNTCP became the National TB Elimination Programme (NTEP) in 2020, with the Ni-kshay digital notification portal, Ni-kshay Poshan Yojana direct-benefit nutritional support (raised to ₹1000 per month in 2024), the Pradhan Mantri TB Mukt Bharat Abhiyaan with Ni-kshay Mitra community adoption, and a national elimination target ahead of the global 2030 goal.

3.

Drug-susceptible TB (for contrast). 2HRZE / 4HR — two months of isoniazid, rifampicin, pyrazinamide and ethambutol, then four months of isoniazid and rifampicin, given daily as weight-band fixed-dose combinations (NTEP moved from thrice-weekly to daily dosing in 2017). Doses: H 5 mg/kg, R 10 mg/kg, Z 25 mg/kg, E 15 mg/kg, with pyridoxine 10 mg daily — essential in older adults to prevent isoniazid neuropathy.

4.

Current MDR/RR-TB regimens — the core of the answer.

Regimen Composition Use

BPaLM — 6 months Bedaquiline + Paretomanid + Linezolid 600 MDR/RR-TB, age ≥14 y. Drop moxifloxacin → BPaL (preferred) mg + Moxifloxacin if fluoroquinolone-resistant (pre-XDR). Not for pregnancy/breastfeeding (no pretomanid safety data)

BDLLfxC — 6 months Bedaquiline + Delamanid + Linezolid 600 mg Alternative 6-month regimen; usable in pregnancy, + Levofloxacin + Clofazimine breastfeeding and children. Becomes BDLC if fluoroquinolone-resistant. Requires no prior exposure >1 month to bedaquiline, delamanid or linezolid 9-month all-oral Bedaquiline-containing (BPaLM or BDLLfxZ) Fluoroquinolone-susceptible only — must not be used in pre-XDR-TB Longer individualised Built from Groups A → B → C When short regimens are unsuitable, and 18–20 months mandatory for CNS, osteoarticular and disseminated multi-organ TB — all short regimens are contraindicated in these

5.

Drug groups and key doses. Group A (include all three) — levofloxacin or moxifloxacin, bedaquiline, linezolid. Group B (add both) — clofazimine, cycloserine or terizidone. Group C (add to complete) — ethambutol, delamanid, pyrazinamide, imipenem-cilastatin or meropenem, amikacin, ethionamide, para-aminosalicylic acid. Doses to quote: bedaquiline 400 mg daily for 2 weeks then 200 mg three times a week for 22 weeks; pretomanid 200 mg daily; linezolid 600 mg daily; moxifloxacin 400 mg daily; levofloxacin 750–1000 mg daily; delamanid 100 mg twice daily; clofazimine 100 mg daily.

6.

Monitoring and geriatric considerations. Monthly sputum smear and culture for conversion; monthly weight; baseline and serial ECG for QT interval (bedaquiline, moxifloxacin, clofazimine and delamanid all prolong QT — correct potassium and magnesium first); monthly CBC, vision and peripheral nerve assessment for linezolid (myelosuppression, optic and peripheral neuropathy — the commonest reason for dose reduction to 300 mg or interruption); liver and renal function; TSH (ethionamide, PAS); psychiatric review (cycloserine — psychosis, depression, seizures); and audiometry if an aminoglycoside is unavoidable — injectable aminoglycosides should be avoided altogether in older adults because of ototoxicity and nephrotoxicity. In the elderly also: dose-adjust for the age-related fall in GFR, review interactions with cardiac and psychotropic drugs, screen for and treat diabetes and malnutrition, and provide family-supported or video-observed treatment rather than daily clinic attendance.

Latest Update (2023 – present)

7.

The WHO Consolidated Guidelines on Tuberculosis, Module 4 (2025 update) now prioritise all-oral 6-month regimens — BPaLM and BDLLfxC — as the standard of care for MDR/RR-TB, with 9-month all-oral regimens reserved for fluoroquinolone-susceptible disease, and CNS, osteoarticular and disseminated TB listed as contraindications to all short regimens. Uptake has accelerated sharply: 34,256 people worldwide started a 6-month regimen in 2024, up from 5,653 in 2023, across 97 countries. WHO also strongly recommended 6 months of levofloxacin (6-Lfx) as preventive treatment for household contacts of MDR/RR-TB in September 2024. India, which carries about 27% of the global rifampicin-resistant TB burden, has rolled out BPaLM nationally under NTEP, with pooled Indian real-world treatment success of about 89.7%, the main toxicities being linezolid-related anaemia (13.4%) and peripheral neuropathy (8.7%).

MNEMONIC ANCHOR

Group A = "B-L-Q" — Bedaquiline, Linezolid, Quinolone (all three always included). Group B = "2 C's" — Clofazimine, Cycloserine.

Regimens = "6 – 6 – 9 – 18" — BPaLM 6 months · BDLLfxC 6 months · all-oral 9 months (FQ-sensitive only) · longer individualised 18–20 months.

NUMERICAL ANCHORS

DOTS has 5 components · drug-susceptible regimen 2HRZE/4HR · bedaquiline 400 mg × 2 weeks → 200 mg thrice weekly × 22 weeks · linezolid 600 mg daily · pretomanid 200 mg daily · moxifloxacin 400 mg daily · delamanid 100 mg BD · clofazimine 100 mg daily · Ni-kshay Poshan Yojana ₹1000/month · India ≈ 27% of global RR-TB · Indian BPaLM success ≈90% · 6-Lfx preventive therapy for MDR contacts.

NAMED EXAMINER TRAPS

(a) RR-TB is managed as MDR-TB — rifampicin resistance alone is enough. (b) The 2021 XDR definition changed — it is no longer "second-line injectable resistance" but resistance to a Group A drug (bedaquiline or linezolid). (c) The 9-month regimen is only for fluoroquinolone-susceptible disease — using it in pre-XDR is a serious error. (d) Short regimens are contraindicated in CNS, osteoarticular and disseminated TB. (e) Avoid injectable aminoglycosides in older adults. (f) Always add pyridoxine with isoniazid in the elderly. (g) Get a baseline ECG before starting — three of the four drugs in BPaLM prolong QT.

15-SECOND ANSWER SKELETON

Definitions of resistance (mono → poly → MDR → RR → pre-XDR → XDR with the 2021 change) → the 5 components of DOTS and the Indian NTEP framework → drug-susceptible regimen for contrast → the four current regimens in a table → Groups A/B/C with doses → monitoring (culture, ECG, CBC, vision, nerves) and geriatric caveats → WHO 2025 Module 4 and the Indian BPaLM roll-out.

EXTRA RECALL BOX — TB IN THE OLDER ADULT (THIS IS WHAT MAKES IT A GERIATRICS ANSWER) Kane's makes three points that must appear: (i) older people of all groups are especially at risk, having lived through a period of higher TB incidence, having probably never received isoniazid preventive therapy, and having predisposing factors — physiological change, malnutrition and underlying disease — that lead to reactivation; they are also at increased risk of primary infection, particularly in long-term care facilities. (ii) TB screening programmes should be implemented in long-term care facilities, with isoniazid 300 mg/day for 9–12 months for skin-test converters who have an abnormal chest film, diabetes, end-stage renal disease, haematological malignancy, steroid or immunosuppressive therapy, or malnutrition. (iii) The single most quotable line: "A useful rule in geriatric care is to suspect tuberculosis when a patient is inexplicably failing." Add that tuberculin skin testing may be falsely negative because of anergy in older people, so an IGRA or a two-step test is preferred.

Exam One-Liners

MDR-TB — resistance to isoniazid + rifampicin.

Pre-XDR — MDR/RR + fluoroquinolone resistance.

XDR (2021) — pre-XDR + resistance to bedaquiline or linezolid.

Preferred regimen — BPaLM for 6 months; drop the M if FQ-resistant.

Regimen usable in pregnancy — BDLLfxC.

Group A drugs — quinolone, bedaquiline, linezolid.

Commonest limiting toxicity — linezolid (marrow, optic and peripheral nerve).

Mandatory baseline test — ECG for QT.

MDR contact prophylaxis — 6 months levofloxacin.

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