tuberculosis

TB infection (LTBI): test with TST or IGRA only when you would treat; exclude active disease first; treat with 4 months rifampin (4R) or 12 weekly doses of rifapentine + isoniazid (3HP) — Canadian TB Standards 2022. Active TB: airborne isolation, 3 sputa for smear/culture + NAAT, then 2 months RIPE → 4 months rifampin + isoniazid, directly observed; notify public health. HIV + TB: start TB treatment first, ART within 2 weeks if CD4 <50, within 8 weeks otherwise — defer in TB meningitis.

do not miss

TB meningitis (subacute headache, cranial nerve palsies, lymphocytic CSF with low glucose) → start RIPE + dexamethasone empirically
miliary TB in the immunosuppressed → may have normal CXR early; culture blood, urine, marrow
starting TB preventive treatment with undiagnosed active TB → rifampin monotherapy → resistance

TB infection (LTBI)

who to test

Only when a positive result would lead to treatment:

close contacts of infectious TB
HIV; before TNF inhibitors, other biologics, JAK inhibitors, transplant, prednisone ≥15 mg/day for ≥1 month, chemotherapy
CKD stage 4–5/dialysis, silicosis, diabetes, fibronodular changes on CXR
recent arrivals (≤2 years) from high-incidence countries, especially with other risk factors

TST vs IGRA

either is acceptable; IGRA preferred if BCG given after infancy or multiple times, or the person is unlikely to return for a TST reading
BCG in infancy rarely causes TST ≥10 mm beyond 10 years
neither test distinguishes infection from active disease — a negative result does not exclude active TB

TST cut-offs (Canadian 8th edition)

induration	positive in
≥5 mm	HIV; recent contact (<2 years); fibronodular disease on CXR; organ transplant; TNF inhibitors/biologics; prednisone ≥15 mg/day; CKD stage 4–5
≥10 mm	everyone else tested — diabetes, silicosis, malnutrition, smoking, heavy alcohol use, haematological malignancy, TST conversion

before treating

symptom review + CXR ± 3 sputa to exclude active TB
baseline LFTs if age >50, liver disease, alcohol use, HIV, pregnancy/postpartum, or hepatotoxic drugs; otherwise monthly clinical review
review rifamycin interactions: warfarin, DOACs, oral contraceptives, antiretrovirals, tacrolimus/ciclosporin, methadone, azoles

regimens

regimen	dosing	notes
4R — first-line	rifampin 10 mg/kg (max 600 mg) daily × 4 months	better completion, less hepatotoxicity than 9H
3HP — first-line	isoniazid 15 mg/kg (max 900 mg) + rifapentine (max 900 mg) weekly × 12 doses	DOT preferred; rifapentine via Health Canada Special Access Programme; flu-like reactions
3HR — alternative	isoniazid + rifampin daily × 3 months	—
9H (or 6H) — alternative	isoniazid 5 mg/kg (max 300 mg) daily	when rifamycins cannot be used; + pyridoxine

Hepatotoxicity: stop if ALT >3× ULN with symptoms or >5× ULN without.

active TB

suspect

cough >2–3 weeks, fever, night sweats, weight loss, haemoptysis
upper-lobe cavitation, hilar/mediastinal nodes, pleural effusion (lymphocytic exudate, raised ADA), miliary pattern
risk: birth or residence in high-incidence country, Indigenous communities with high incidence, contacts, homelessness, incarceration, HIV, immunosuppression

workup

airborne isolation (N95, negative-pressure room) while pending
3 sputa (spontaneous or induced; same day ≥1 h apart is acceptable) → AFB smear, culture (gold standard; weeks), and NAAT (e.g. Xpert MTB/RIF — also detects rifampin resistance) on at least one
bronchoscopy/BAL if unable to produce sputum; tissue biopsy for extrapulmonary disease (culture + histology)
HIV test in everyone with TB; HBV/HCV, baseline LFTs, creatinine, CBC, visual acuity/colour vision
report to public health; contact tracing

treatment — drug-susceptible

2 months isoniazid + rifampin + pyrazinamide + ethambutol (RIPE) → 4 months isoniazid + rifampin, daily, with directly observed or supported therapy.

drug	adult daily dose	key toxicity
isoniazid (H)	5 mg/kg (max 300 mg)	hepatitis, peripheral neuropathy
rifampin (R)	10 mg/kg (max 600 mg)	hepatitis (cholestatic), CYP induction, orange secretions, thrombocytopaenia, flu-like illness
pyrazinamide (Z)	20–25 mg/kg	hepatitis (most hepatotoxic), hyperuricaemia/gout, arthralgia
ethambutol (E)	15–20 mg/kg	optic neuritis — ↓ acuity, red-green colour loss; renally dosed

pyridoxine 25–50 mg daily with isoniazid if diabetes, CKD, HIV, malnutrition, alcohol/substance use, seizure disorder, pregnancy/breastfeeding
stop ethambutol once susceptibility to isoniazid and rifampin confirmed
extend continuation to 7 months (9 total) if cavitation on baseline CXR and positive sputum culture at 2 months
TB meningitis: 12 months total + dexamethasone (tapered over 6–8 weeks)
TB pericarditis: 6 months; steroids reduce constriction but not mortality — expert input
monitoring: monthly LFTs and clinical review; monthly visual acuity/colour vision on ethambutol; sputum every 2 weeks until smear-negative, then at 2 months and near completion

hepatotoxicity

stop all hepatotoxic drugs if ALT >3× ULN with symptoms or jaundice, or >5× ULN without symptoms
severe/infectious TB while waiting → non-hepatotoxic bridge (ethambutol + fluoroquinolone ± aminoglycoside)
reintroduce sequentially once ALT <2× ULN: rifampin → isoniazid → pyrazinamide (often omitted; then 9 months HR)

ending airborne isolation

suspected TB: 3 negative sputum AFB smears, or an alternative diagnosis
confirmed: ≥2 weeks effective therapy, clinical improvement, and negative smears — per local IPAC before discharge to a congregate setting

TB and HIV

start TB treatment first; ART within 2 weeks if CD4 <50 — STRIDE (2011) — and within 8 weeks otherwise
TB meningitis: defer ART ~8 weeks — Török (2011): immediate ART → more severe adverse events, no survival gain
rifampin interactions: dolutegravir 50 mg BID; bictegravir contraindicated; rifabutin with boosted PIs
paradoxical IRIS common — continue both; see HIV opportunistic infections

drug-resistant TB

rifampin resistance on NAAT → treat as MDR/RR-TB with the provincial TB programme
isoniazid mono-resistance: rifampin + ethambutol + pyrazinamide + levofloxacin × 6 months
all-oral 6-month regimens (bedaquiline, pretomanid, linezolid ± moxifloxacin) are now standard for MDR/RR-TB — specialist-led

nontuberculous mycobacteria (NTM)

Diagnosis (ATS/ERS/ESCMID/IDSA 2020) — all three:

pulmonary symptoms
nodular or cavitary opacities, or bronchiectasis with multiple small nodules on HRCT
microbiology: ≥2 separate positive sputum cultures (same species), or 1 BAL/wash, or biopsy with granulomas + culture

MAC lung disease (macrolide-susceptible):

nodular-bronchiectatic: azithromycin + ethambutol + rifampin three times weekly
cavitary or severe: daily regimen + IV amikacin initially
treat ≥12 months after sputum culture conversion; refractory at 6 months → add amikacin liposome inhalation
M. abscessus, M. kansasii: ID/respirology
not transmissible person-to-person — no isolation, not notifiable

traps

treating LTBI before excluding active TB with CXR ± sputum
relying on a negative IGRA/TST to exclude active TB
9H as default — rifamycin-based regimens are first-line in Canada
forgetting rifampin interactions (warfarin, DOACs, contraceptives, ART, transplant immunosuppression)
stopping isolation because the patient “looks better” before smears are negative
starting ART immediately in TB meningitis
ethambutol without baseline and monthly visual testing