MedCompanion

Active Tuberculosis

Mycobacterial

Source: IDMP View on spectrum chart →
Patient + scenario modifiers
Patient
Clinical scenario / source

Annotations only — chart still shows the full chemistry of each drug.

1. Clinical Syndrome

Symptomatic disease from Mycobacterium tuberculosis with positive culture / PCR (Xpert MTB/RIF) / smear, typically with radiographic + clinical findings. Pulmonary (most common — cough, fever, weight loss, night sweats, hemoptysis, upper-lobe cavities) and extrapulmonary (lymphadenitis, vertebral / Pott's, meningitis, pleuritis, miliary, abdominal, GU, cutaneous).

Excludes: latent TB infection (LTBI — positive IGRA/TST without active disease, separate syndrome), atypical mycobacterial disease (MAC, M. kansasii — different regimens).

2. Pathogens

Consider the patient: HIV co-infection (start ART within 2 weeks of TB tx if CD4 <50; within 8 weeks otherwise — but with IRIS monitoring), prior TB / treatment history (drug resistance risk), country of origin (MDR prevalence), age (extremes have worse outcomes), pregnancy.

Consider the case: Drug-susceptible vs MDR/XDR (Xpert MTB/RIF screens rifampin resistance same-day), site (CNS / pericardial → add steroids), severity (sepsis), source isolation needs (airborne precautions until 3 negative AFB smears + clinical response).

Common

3. Empiric Therapy

TierFirst choiceAlternativesDurationComments
Outpatient
  • 10 mg/kg (max 600 mg) · PO daily · PO · 6 months total (RIPE × 2 mo intensive + HR × 4 mo continuation)
  • 5 mg/kg (max 300 mg) + pyridoxine 25–50 mg · PO daily · PO · 6 months total
  • 25 mg/kg (max 2 g) · PO daily · PO · 2 months intensive only
  • 15–25 mg/kg (max 1.6 g) · PO daily · PO · 2 months intensive only (can stop sooner if isolate fully susceptible to INH + RIF + PZA)
  • 300 mg (dose-adjust per ART) · PO daily · PO

    **Substitute for rifampin in HIV co-infection** — less ART interaction.

**Standard 6-month regimen: RIPE × 2 months intensive → HR × 4 months continuation.** Extend continuation phase to 7 months (9 mo total) for cavitary disease + still-positive cultures at 2 months. CNS TB: 9–12 months total. Bone/joint: 6–9 months.**Drug-susceptible TB.** DOT (directly observed therapy) preferred — improves adherence + completion rates. State / county TB clinic typically manages. **HIV co-infection**: start ART within 2 weeks if CD4 <50 (mortality benefit), 8 weeks if CD4 ≥50 (reduces paradoxical TB-IRIS). **Cavitary disease + positive culture at 2 months** = extend continuation to 7 months.
Admitted to ward
  • 10 mg/kg · PO/IV daily · IV/PO
  • 5 mg/kg + pyridoxine · PO/IV daily · IV/PO
  • 25 mg/kg · PO daily · PO
  • 15–25 mg/kg · PO daily · PO
—6 months total (longer for CNS or bone)**Hospitalized for diagnosis confirmation, severe disease, or airborne isolation needs.** Negative pressure isolation × 3 negative AFB smears (typically 2 weeks of tx) + clinical improvement. **Add corticosteroids** for TB meningitis (dexamethasone tapered over 8 weeks — mortality benefit) + TB pericarditis (prednisone). **CNS TB regimen**: 9–12 months total.
ICU — Pseudomonas risk
  • 400 mg PO daily × 2 wk → 200 mg 3×/wk · — · PO
  • Pretomanid 200 mg PO daily · — · PO

    Not yet seeded. Combined with bedaquiline + linezolid (BPaL) or + linezolid + moxifloxacin (BPaLM) for MDR-TB.

  • 600 mg · PO daily · PO

    Often dose-reduced to 300 mg daily after weeks due to cytopenias.

  • 100 mg · PO daily · PO

    Adjunct in pre-XDR / XDR regimens.

BPaL/BPaLM = 6 months (revolutionary shortening from older 18+ months MDR-TB courses); pre-XDR / XDR individualized.**MDR-TB / XDR-TB or severe TB requiring ICU.** **WHO 2022**: BPaL (bedaquiline + pretomanid + linezolid) × 6 months for select MDR-TB. **Specialist + state TB program** management mandatory. **Monthly ECG** for QT (bedaquiline + clofazimine + FQ all QT-prolonging). **CBC monthly** for linezolid cytopenias.

4. Directed Therapy

Standard 6-month RIPE → HR for DS-TB: 2 months intensive (4 drugs) + 4 months continuation (HR alone). Extend continuation to 7 months (total 9) for cavitary + positive 2-month cultures. CNS TB: 9–12 months total + dexamethasone. Bone/joint TB: 6–9 months.

MDR-TB (RIF + INH resistant): WHO 2022 BPaL (bedaquiline + pretomanid + linezolid) × 6 months for select cases — game-changer from old 18+ month regimens. Pre-XDR / XDR: individualized; specialist-managed.

Adjuncts:

  • Pyridoxine 25–50 mg daily for all adults on INH — prevents neuropathy.
  • Vitamin K to newborn of mother on rifampin.
  • Corticosteroids: dexamethasone (taper over 6–8 weeks) for TB meningitis (mortality benefit); prednisone (taper) for TB pericarditis.
  • HIV co-infection: start ART within 2–8 weeks; rifabutin substitute for rifampin; monitor for IRIS.
  • DOT (directly observed therapy) — adherence is the biggest single predictor of cure.

Monitoring: monthly LFTs (hepatotoxicity from RIF + INH + PZA), vision (ethambutol), uric acid (PZA), sputum AFB monthly until conversion. 3 negative AFB smears + clinical response to clear airborne isolation.

Drug interactions (rifampin specifically): warfarin, OCPs (use backup), HIV ART (use rifabutin instead), DOACs, statins, tacrolimus, methadone, opioids, anticonvulsants, voriconazole (contraindicated), corticosteroids (dose-adjust). Drug interaction screen MANDATORY before starting.

5. Monitoring

Sputum AFB monthly until 2 consecutive negative cultures (treatment failure if still positive at 4 months — repeat DST, suspect resistance, reconfirm adherence). LFTs monthly for first 3 months then as clinically indicated; stop tx for AST/ALT >3× ULN with symptoms or >5× without. Vision testing monthly for ethambutol. Pyridoxine 25–50 mg daily for INH neuropathy prophylaxis.

Resolution markers: fever, weight gain, sputum conversion (by 2 months typically), radiographic improvement (lags clinical by months).

Notifiable disease — report to local + state health departments at diagnosis.

Pearls

RIPE × 2 mo intensive → HR × 4 mo continuation = 6 months total for DS-TB. Always pyridoxine with INH in adults. HIV co-infection: rifabutin for rifampin + start ART within 2–8 weeks. MDR-TB: BPaL × 6 months is the modern revolution. Hepatotoxicity is the dose-limiting AE — monthly LFTs, stop at AST/ALT >3× ULN with symptoms. DOT preferred — adherence dominates cure rates. CNS TB + pericarditis = steroids. Notifiable disease — local + state public health involvement standard.

References