Mycobacterium tuberculosis grows slowly, hides inside macrophages and caseous lesions, and has a waxy, mycolic-acid-rich cell wall. Three consequences shape every regimen:

• Combination therapy is mandatory. Any large bacterial population contains a few naturally resistant organisms. A single drug kills the susceptible ones and selects the resistant ones; two or more active drugs prevent this.
• Treatment is long. Slowly dividing and dormant bacilli need months of exposure. The intensive phase kills the rapidly multiplying population; the continuation phase sterilizes the persisters.
• Adherence is the main safety issue. Missed doses cause relapse and acquired resistance, so programs use directly observed or supported treatment.

Drug-susceptible pulmonary TB

• Standard 6-month regimen (2HRZE/4HR): isoniazid, rifampin, pyrazinamide, and ethambutol daily for 2 months (intensive phase), then isoniazid and rifampin for 4 months (continuation phase). Ethambutol can be stopped early once susceptibility to isoniazid and rifampin is confirmed
• 4-month regimen for people 12 years and older weighing at least 40 kg: isoniazid, rifapentine, moxifloxacin, and pyrazinamide (2 months), then isoniazid, rifapentine, and moxifloxacin (2 months). Not for pregnancy, breastfeeding, most extrapulmonary TB, or HIV with CD4 below 100 cells/µL
• Children with non-severe TB: 4 months of standard drugs (2HRZ(E)/2HR)
• Fixed-dose combination tablets, dosed by weight band, reduce pill burden and prevent selective omission of one drug

Drug-resistant TB

• MDR/RR-TB = resistant to at least rifampin (MDR = isoniazid and rifampin)
• BPaLM (bedaquiline, pretomanid, linezolid, moxifloxacin) for 6 months, or BPaL if fluoroquinolone-resistant, for people aged 14 years and older — replacing the old 18–24-month regimens with daily injectables. BPaLM/BPaL is not used in pregnancy or under 14 years; other 6-month all-oral regimens are chosen by the specialist for these groups

TB infection (latent TB) — TB preventive treatment

• 3HP: isoniazid + rifapentine once weekly for 12 doses
• 4R: rifampin daily for 4 months
• 3HR: isoniazid + rifampin daily for 3 months
• Isoniazid alone for 6–9 months is an alternative

Usual adult daily doses (verify against a current reference)

Pyridoxine (vitamin B6) is indicated for clients at risk of neuropathy: diabetes, HIV, alcohol use, malnutrition, chronic kidney disease, pregnancy and breastfeeding, and people with seizure disorders.

Drug-induced liver injury (DILI) is the most common serious problem with the first-line regimen. Isoniazid, rifampin, and pyrazinamide can all cause it; ethambutol does not.

Contraindications and cautions

• Acute liver disease or prior severe isoniazid-related hepatitis — isoniazid contraindicated
• Pyrazinamide: avoid in acute gout and severe liver disease
• Ethambutol: use caution in young children who cannot report vision changes and in kidney failure (dose interval adjusted)
• Bedaquiline and fluoroquinolones: caution with a prolonged QTc, hypokalemia, hypomagnesemia, or other QT-prolonging drugs

Pregnancy and lactation

• The first-line drugs (isoniazid, rifampin, ethambutol) are used in pregnancy because untreated TB is far more dangerous; many programs, including WHO, also include pyrazinamide. Give pyridoxine
• The 4-month rifapentine–moxifloxacin regimen is not used in pregnancy or breastfeeding
• Aminoglycosides (streptomycin, amikacin) are avoided in pregnancy — fetal ototoxicity
• Breastfeeding may continue during first-line treatment; the infant is assessed for TB and preventive treatment

Interactions

• Rifampin is a strong inducer of CYP450 enzymes (especially CYP3A4). It lowers the level of hormonal contraceptives (implants, pills, patches, rings — use a copper IUD, DMPA, or barrier method), warfarin, direct oral anticoagulants, many antiretrovirals (protease inhibitors, some integrase inhibitors need dose adjustment), methadone (withdrawal), azole antifungals, sulfonylureas, corticosteroids, calcineurin inhibitors, and some antiseizure drugs. Always ask about every medication before starting
• Isoniazid inhibits metabolism of phenytoin and carbamazepine (toxicity); alcohol increases hepatotoxicity — avoid it
• Antacids containing aluminum reduce isoniazid absorption; separate the doses
• Fluoroquinolones chelate with calcium, iron, magnesium, zinc, and antacids — separate by several hours
• Linezolid + SSRIs or other serotonergic drugs → serotonin syndrome; large amounts of tyramine-rich food are limited

Before treatment

• Baseline liver tests (AST/ALT, bilirubin), CBC, creatinine, uric acid if pyrazinamide is used, HIV test for everyone with TB, hepatitis B and C screening if at risk, glucose/A1C
• Visual acuity (Snellen) and red-green color vision (Ishihara) before ethambutol
• Baseline ECG and potassium/magnesium before bedaquiline or fluoroquinolones
• Pregnancy status and contraception plan (rifampin interaction)

During treatment

1. Watch for hepatotoxicity at every visit — ask about nausea, vomiting, loss of appetite, abdominal pain, dark urine, jaundice, and fatigue. Hold the drugs and notify the provider if symptoms appear. Typical rule: stop hepatotoxic drugs if ALT is more than 3 times the upper limit of normal with symptoms or more than 5 times without symptoms, or bilirubin rises
2. Routine monthly liver tests are recommended for clients with baseline abnormalities, liver disease, alcohol use, HIV, pregnancy or the postpartum period, or older age
3. Monthly vision check on ethambutol (acuity and color); stop and report any change
4. Ask about numbness, tingling, or burning of hands and feet (isoniazid, linezolid)
5. Drug-resistant regimens: ECG at baseline and during treatment (QTc; hold and report QTc above 500 ms), CBC for linezolid, electrolytes
6. Sputum smear and culture monthly until two consecutive negative cultures; a positive culture at 2 months prompts review of adherence and resistance (therapy may be extended); a positive culture at 4 months or later = treatment failure
7. Directly observed or video-observed treatment and adherence support; track every missed dose
8. Airborne precautions (negative-pressure room, fit-tested N95 respirator) for infectious pulmonary TB in hospital until the provider determines the client is no longer infectious
9. Weight monthly — doses are weight-based and weight gain is a sign of response

• Take every dose for the full course, even after you feel better in a few weeks. Stopping early causes relapse and drug-resistant TB
• Take isoniazid and rifampin on an empty stomach at the same time each day; if nausea occurs, the provider may allow a small snack or bedtime dosing
• Rifampin turns urine, sweat, and tears orange-red — this is expected; soft contact lenses can be permanently stained
• Use a copper IUD, DMPA injection, or a barrier method (not pills, patch, ring, or implant) during rifampin therapy and for about a month after
• Do not drink alcohol; avoid acetaminophen in large amounts and herbal supplements unless approved
• Report immediately: yellow skin or eyes, dark urine, persistent nausea or abdominal pain (liver); blurred vision or trouble telling red from green (ethambutol); numbness or tingling; joint pain (pyrazinamide); palpitations or fainting (bedaquiline)
• Cover coughs, ventilate rooms, and follow home isolation advice until told you are not infectious
• Household contacts should be screened and offered preventive treatment

Isoniazid overdose — a classic emergency. Isoniazid depletes pyridoxine, so the brain makes less GABA.

• Triad: refractory seizures, severe metabolic (lactic) acidosis, and coma, typically within 30 minutes to 2 hours
• Antidote: IV pyridoxine — gram for gram of the isoniazid ingested; if the amount is unknown, about 5 g IV in adults (70 mg/kg in children, up to 5 g). Benzodiazepines are given with it; seizures often do not stop without pyridoxine
• Supportive care: airway, correction of acidosis

Drug-induced hepatitis — stop all hepatotoxic drugs; once liver tests recover, drugs are reintroduced one at a time under the provider's direction.

Ethambutol optic neuritis — stop immediately; urgent eye evaluation.

Rifampin hypersensitivity — flu-like syndrome, thrombocytopenia, hemolysis, or acute kidney injury (more likely with intermittent dosing) — stop and do not rechallenge after severe reactions.

QT prolongation (bedaquiline, fluoroquinolones) — ECG, correct potassium and magnesium; torsades is treated with IV magnesium.

• TB is always treated with multiple drugs to prevent resistance; adherence (DOT) is the priority
• Standard regimen 2HRZE/4HR (6 months); 4-month rifapentine–moxifloxacin regimen at ≥ 12 years and ≥ 40 kg, not in pregnancy
• Isoniazid: hepatotoxicity, peripheral neuropathy → pyridoxine (B6), raises phenytoin levels, avoid alcohol
• Rifampin: orange-red body fluids; strong enzyme inducer — contraceptives, warfarin, antiretrovirals fail
• Pyrazinamide: hepatotoxicity, hyperuricemia/gout
• Ethambutol: optic neuritis, red-green color vision — baseline and monthly vision tests
• Hepatotoxicity symptoms → hold drugs and notify the provider
• Isoniazid overdose: seizures + acidosis → IV pyridoxine
• MDR-TB: 6-month all-oral BPaLM/BPaL; bedaquiline → QT, linezolid → marrow suppression and neuropathy
• TB infection: 3HP, 4R, or 3HR
• Everyone with TB gets an HIV test