Drug-resistant tuberculosis (MDR / pre-XDR / XDR)
Encounter flow
12/12 authoredCanonical 12-phase frame with authored status for this dossier.
Frame
Confirm MDR / pre-XDR / XDR via Xpert + DST + WGS; classify resistance pattern per WHO 2021 redefinition
Resistance pattern documented
Patient inputs (19)
Drug doses; pregnancy considerations (WHO 2022)
Bedaquiline / pretomanid limited pregnancy data (WHO 2022 Module 4)
Resistance risk (WHO 2022)
DDI esp ART, QT-prolongers, MAOI for linezolid serotonergic (WHO 2022)
Diagnostic + monitoring conversion (WHO 2022)
Rapid resistance screen (WHO 2022 Xpert MTB/RIF Ultra + XDR recommendation)
Phenotypic DST gold standard (WHO 2022)
HIV co-infection alters regimen + ART interactions (WHO 2022)
Linezolid myelosuppression baseline (ZeNix NEJM 2022)
Bedaquiline / pretomanid hepatotox (Nix-TB NEJM 2020)
Drug dosing (WHO 2022)
QT correction — bedaquiline QT monitoring (WHO 2022)
Disease extent (WHO 2022)
Bedaquiline + moxifloxacin QT monitoring (WHO 2022 aDSM)
Linezolid optic neuropathy + ototoxicity baseline (ZeNix NEJM 2022; WHO 2022 aDSM)
Genotypic resistance (WHO 2022 LPA / WGS recommendation)
Cavitary, miliary, pleural (ATS/IDSA/CDC 2022)
TB meningitis / tuberculoma (ATS/IDSA/CDC 2022)
OI prophylaxis + ART timing (WHO 2022)
* = hard-required. Engine cannot meaningfully run until these are filled.
Severity triggers (10)
- informationallife_threateningtb_meningitis_or_miliaryTB meningitis or miliary disease with confirmed MDR (IDSA 2024)Trigger could not be auto-evaluated — needs clinician judgement.
- informationalseverelinezolid_optic_neuropathyVision change, colour vision loss, or visual field change on linezolid (IDSA 2024)Trigger could not be auto-evaluated — needs clinician judgement.
- informationalseverebedaquiline_qtc_prolongationQTc >500 ms or rising 60 ms on bedaquiline (IDSA 2024)Trigger could not be auto-evaluated — needs clinician judgement.
- informationalseverelinezolid_myelosuppressionHgb drop ≥2 g/dL, ANC <500, plt <50K on linezolid (IDSA 2024)Trigger could not be auto-evaluated — needs clinician judgement.
- informationalseverepregnancy_with_drtbPregnancy in MDR / pre-XDR / XDR-TB (IDSA 2024)Trigger could not be auto-evaluated — needs clinician judgement.
- informationalseverehiv_coinfection_drtbHIV-positive patient with DR-TB (IDSA 2024)Trigger could not be auto-evaluated — needs clinician judgement.
- informationalseveretreatment_failure_or_relapseSputum culture not converting at 4 mo or relapse (IDSA 2024)Trigger could not be auto-evaluated — needs clinician judgement.
- informationalsevereculture_non_conversion_at_2_monthsSputum culture still positive at month 2 of BPaL/BPaLM (WHO 2022 — early marker of poor outcome)Trigger could not be auto-evaluated — needs clinician judgement.
- informationalseverexdr_tb_individualized_regimen_requiredXDR-TB confirmed (MDR + FQ + LZD/BDQ resistance per WHO 2021 redefinition)Trigger could not be auto-evaluated — needs clinician judgement.
- informationalmoderatecontact_tracing_and_public_health_notificationEvery confirmed DR-TB case (active or latent in close contact) — public health notification and contact tracing requiredTrigger could not be auto-evaluated — needs clinician judgement.
Workflow calculators
Run this disease's risk and dosing calculators inline.
Recommended regimen
BPaL / BPaLM 6-month short-course MDR/pre-XDR/XDR-TB (IDSA 2024)- bedaquilinefirst linediarylquinoline400 mg daily × 2 wks then 200 mg three times weekly • PO • daily then 3×/wktriggers: MDR_TB, pre_XDR, XDR_TBBackbone of BPaL/BPaLM; QT prolonging (WHO 2022; Nix-TB NEJM 2020)rxcui 1364504
- pretomanidfirst linenitroimidazole200 mg • PO • daily for 26 wkstriggers: MDR_TB, pre_XDR, XDR_TBNix-TB (NEJM 2020) / ZeNix (NEJM 2022); pretomanid + bedaquiline + linezolid 6 morxcui 2198359
- linezolidfirst lineoxazolidinone600 mg daily (or 1200 in severe per WHO 2022) • PO • dailytriggers: MDR_TB, pre_XDR, XDR_TBZeNix (NEJM 2022) — 600 mg × 26 wks balances efficacy + toxicityrxcui 190376
- moxifloxacinadd onfluoroquinolone400 mg • PO • dailytriggers: MDR_TB_BPaLM_eligible_no_FQ_resistanceTB-PRACTECAL (NEJM 2022) — added to BPaL as BPaLM for MDR-TBrxcui 139462
- pyridoxine_b6add onvitamin50–100 mg • PO • dailytriggers: linezolid_or_INHReduces neuropathy (WHO 2022)rxcui 684879
outpatient playbook — drug actions (1)
- 1. BPaL or BPaLMper regimen • PO • per regimentrigger: MDR / pre-XDR / XDR (WHO 2022)WHO 2022; ZeNix NEJM 2022; TB-PRACTECAL NEJM 2022
Auto-drafted A&P note
outpatientSubjective
- Possible entry pathways: TB with failed first-line treatment, contact with DR-TB, or DST showing INH + RIF resistance (WHO 2022 Module 4); Xpert MTB/RIF positive with rifampicin resistance (WHO 2022 rapid-diagnostics recommendation); Contact with confirmed MDR-TB case (WHO 2022 contact-investigation guidance).
Objective
- No vitals, labs, or imaging entered for this encounter.
Assessment
**Drug-resistant tuberculosis (MDR / pre-XDR / XDR)** (id.tb_drug_resistant.v1). Phenotype framing: MDR vs pre-XDR vs XDR; mixed infection vs reinfection vs relapse (IDSA 2024) Scope: Confirm MDR / pre-XDR / XDR via Xpert + DST + WGS; classify resistance pattern per WHO 2021 redefinition No severity triggers fired against current inputs.
Plan
Regimen axis: **BPaL / BPaLM 6-month short-course MDR/pre-XDR/XDR-TB (IDSA 2024)**. 1. bedaquiline 400 mg daily × 2 wks then 200 mg three times weekly PO daily then 3×/wk (diarylquinoline, first line) — Backbone of BPaL/BPaLM; QT prolonging (WHO 2022; Nix-TB NEJM 2020) 2. pretomanid 200 mg PO daily for 26 wks (nitroimidazole, first line) — Nix-TB (NEJM 2020) / ZeNix (NEJM 2022); pretomanid + bedaquiline + linezolid 6 mo 3. linezolid 600 mg daily (or 1200 in severe per WHO 2022) PO daily (oxazolidinone, first line) — ZeNix (NEJM 2022) — 600 mg × 26 wks balances efficacy + toxicity 4. moxifloxacin 400 mg PO daily (fluoroquinolone, add on) — TB-PRACTECAL (NEJM 2022) — added to BPaL as BPaLM for MDR-TB 5. pyridoxine_b6 50–100 mg PO daily (vitamin, add on) — Reduces neuropathy (WHO 2022) Setting playbook (outpatient) — DOT regimen, monitoring, contact tracing, HIV co-management (IDSA 2024) 6. BPaL or BPaLM per regimen PO per regimen — MDR / pre-XDR / XDR (WHO 2022) (WHO 2022; ZeNix NEJM 2022; TB-PRACTECAL NEJM 2022) Non-pharmacologic actions: - DOT (directly observed therapy) (IDSA 2024) - Contact tracing (IDSA 2024) - Infection control (mask, ventilation) (IDSA 2024) - Vaccinations (avoid live in HIV/cd4) (IDSA 2024) AVOID / contraindication checks: - Bedaquiline QTc monitoring baseline and monthly (IDSA 2024) - Pretomanid hepatotoxicity LFT q1m (IDSA 2024) - Linezolid CBC q2w x8_then_q1m (IDSA 2024) - Linezolid vision audiometry q1m (IDSA 2024) - Linezolid MAOI serotonergic DDI (IDSA 2024) - Moxifloxacin tendinopathy QTc (IDSA 2024)
Monitoring
Regimen monitoring: - sputum culture monthly to conversion (IDSA 2024) - CBC q2w x8 then q1m (IDSA 2024) - LFT q1m (IDSA 2024) - BMP K Mg q2w (IDSA 2024) - ECG QTc baseline 2w 4w 8w then q1m (IDSA 2024) - vision audiometry q1m on linezolid (IDSA 2024) Setting (outpatient) monitoring: - Per regimen schedule (IDSA 2024) Follow-up plan: TB clinic monthly; contact tracing; HIV care; nutrition (WHO 2022) - Close-out criterion: Follow-up booked Monitoring phase: Monthly sputum culture until conversion then q3 mo; CBC q2 wks x 8 then q1 mo on linezolid; LFT q1 mo; ECG q2 wks x 4 then q1 mo; vision + audiometry q1 mo on linezolid (WHO 2022 aDSM; ZeNix NEJM 2022)
Disposition
Current setting: outpatient — DOT regimen, monitoring, contact tracing, HIV co-management (IDSA 2024) Disposition criteria: - Continue DOT (IDSA 2024) Escalation triggers (move to higher acuity): - Severe AE (vision loss, neuropathy, hepatitis, QTc) → adjust regimen (IDSA 2024) - Treatment failure → DST + repeat workup (IDSA 2024)
Earlier-Return Triggers
Return-precaution thresholds (watch for): - [LIFE_THREATENING] TB meningitis or miliary disease with confirmed MDR (IDSA 2024) - [SEVERE] Vision change, colour vision loss, or visual field change on linezolid (IDSA 2024) - [SEVERE] QTc >500 ms or rising 60 ms on bedaquiline (IDSA 2024)
Citations
- WHO 2022 consolidated guidelines on TB treatment (Module 4 drug-resistant) [PMID:32130813](https://pubmed.ncbi.nlm.nih.gov/32130813/) - Cited evidence (PMID 36053506) [PMID:36053506](https://pubmed.ncbi.nlm.nih.gov/36053506/) - Cited evidence (PMID 36546625) [PMID:36546625](https://pubmed.ncbi.nlm.nih.gov/36546625/) Last reconciled with current guidelines: 2026-05-22.
- WHO 2022 consolidated guidelines on TB treatment (Module 4 drug-resistant) — PMID:32130813
- Cited evidence (PMID 36053506) — PMID:36053506
- Cited evidence (PMID 36546625) — PMID:36546625