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1ïžâ£ MDR / XDR Definitions (WHO 2021 Update)
- MDR-TB: R to INH + Rifampin
- Pre-XDR-TB: MDR + FQ R
- XDR-TB: MDR + FQ R + bedaquiline OR linezolid R
- Old XDR (pre-2021): MDR + FQ R + aminoglycoside R
2ïžâ£ BPaL/BPaLM Patient Selection
- Pulmonary MDR / Pre-XDR / XDR-TB ⥠14 yr
- HIV co-infection ok
- Pregnancy / lactation: caution (some data, drug interactions with ART)
- Diabetes / hepatic / renal disease â adjust carefully
- Counsel on linezolid bone marrow toxicity (monthly CBC)
- QTc baseline + monitor (bedaquiline)
3ïžâ£ TB Drug Resistance Testing
- GeneXpert MTB/RIF â rapid (1-2 hr) rifampin resistance + TB detection; first-line WHO
- Xpert MTB/XDR â extended panel: INH, FQ, aminoglycoside R
- Sequencing: comprehensive (whole genome)
- AST cultures: gold standard but slow (4-12 wk)
4ïžâ£ HIV + TB
- TB is leading cause of death in HIV globally
- IRIS (Immune Reconstitution Inflammatory Syndrome) when ART started
- Drug interactions: rifampin + most ART â enzyme inducer
- Switch rifampin â rifabutin for most ART regimens
- Or use rifampin + DTG-based regimen (compatible)
- èµ· ART 2-8 wk after TB treatment in non-CNS, 2-4 wk in CNS
5ïžâ£ Pregnancy + TB Treatment
- Donât delay treatment
- RIPE all considered safe except occasional concern about PZA (US slightly more cautious than WHO)
- Pyridoxine for INH mandatory (pyridoxine increased need in pregnancy)
- Streptomycin contraindicated (8th nerve fetal damage)
- DOT + close monitoring
6ïžâ£ Drug Levels (TDM)
- Useful in:
- Treatment failure
- HIV
- Diabetes (PK changes)
- Malabsorption
- Drug interactions
- INH, rifampin, ethambutol levels
- Specialty labs
7ïžâ£ Renal / Hepatic Adjustment
- Renal failure: ethambutol, PZA, aminoglycosides â reduce dose / extend interval; INH + rifampin generally OK
- Hepatic disease:
- Mild-moderate: INH or PZA reduce, monitor closely
- Severe: use rifampin + ethambutol + FQ + injectable (no INH, no PZA)
8ïžâ£ TB Stewardship
- Empirical CAP â donât auto-cover TB unless suspicion (cavitary, weight loss, night sweats, immigrant, immunocompromise)
- Donât initiate single-drug ANY anti-TB drug (selects resistance)
- Always combination + correct regimen
- éå ± mandatory
- DOT / vDOT