Tuberculosis — Clinical Reference

Clinical suspicion: cough >2 weeks, fever, night sweats, weight loss, hemoptysis + risk factors (close contact, HIV, immunosuppression, healthcare worker, incarceration/congregate setting).

Diagnostic pathway

1 · Clinical suspicion + CXR

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CXR suggestiveUpper-lobe infiltrate, cavitation, fibronodular change → proceed to microbiologic testing

CXR equivocalCT chest to assess extent/complications

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2 · Send sputum: smear + Xpert MTB/RIF + culture

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3 · Result-driven pathway (see Investigations tab)

Imaging

CXR

Upper lobe infiltrate, cavitation, fibronodular scarring — classic post-primary pattern

CT chest

Use when CXR equivocal, or to assess extent/complications, or to reconcile discordant smear/imaging results at treatment completion

Microbiologic tests

Test	Detects	Turnaround	Notes
AFB smear microscopy	Bacilli load (semi-quantitative)	Hours	Sensitivity ~50–60%; negative does not exclude TB
Culture (liquid MGIT / solid LJ)	Gold standard confirmation + viability	Liquid 1–3 wks; solid 3–8 wks	Required for cure confirmation & DST
Phenotypic DST	Resistance to RIF/INH/PZA/EMB/2nd-line	1–3 wks post-growth	Gold standard for resistance
GeneXpert MTB/RIF (or Ultra)	MTB DNA + rifampicin resistance (rpoB)	~2 h	WHO-recommended initial test; Ultra more sensitive, esp. smear-neg/HIV+
Line probe assay — 1st-line	katG/inhA (INH); rpoB (RIF)	1–2 days	Confirms Xpert RIF-resistance + adds INH data
Line probe assay — 2nd-line	gyrA/gyrB (FQ), rrs/eis (aminoglycosides/capreomycin)	1–2 days	Used once MDR confirmed, to guide regimen
Whole genome sequencing	Comprehensive resistance profile + strain typing	Days	Reference labs / MDR cases; not routine

GeneXpert is the WHO-recommended initial diagnostic test in place of smear alone where available.

PCR/NAAT test comparison

Test	Detects	When used
PCR MTB/RIF (Xpert MTB/RIF or Ultra)	MTB DNA + rifampicin resistance (rpoB) only	Initial diagnostic test for all presumptive TB
"PCR TB" (generic NAAT)	MTB DNA presence only — umbrella term (Xpert, LAMP, in-house PCR); doesn't specify resistance markers	Clarify exact assay when this term is used
PCR MDR-TB (1st-line LPA, e.g. GenoType MTBDRplus)	Rifampicin (rpoB) + isoniazid (katG, inhA) resistance	Reflex after Xpert flags RIF-resistance, to confirm MDR status
PCR MTB/XDR (Xpert MTB/XDR or 2nd-line LPA)	Fluoroquinolone (gyrA/gyrB) + injectable (rrs/eis) ± high-dose INH resistance	Reflex after MDR confirmed, to stage pre-XDR/XDR and select regimen

Cascade: Xpert MTB/RIF → if RIF-resistant → LPA/PCR MDR-TB → if MDR confirmed → Xpert MTB/XDR or 2nd-line LPA.

Standard regimen — drug-susceptible TB

2HRZE / 4HR

Intensive phase 2 months (4 drugs) → continuation phase 4 months (2 drugs)

Weight-based doses — Thai NTP Table 5.1 (adults >15y)

Weight	H (mg)	R (mg)	Z (mg)	E (mg)
35–49 kg	300	450	1,000	800
50–69 kg	300	600	1,500	1,000
>70 kg	300	600	2,000	1,200

mg/kg equivalents: H 4–6, R 8–12, Z 20–30, E 15–20 mg/kg/day. Weight <35 or >70 kg → calculate directly by mg/kg. H may be adjusted by NAT2 acetylator genotype where available.

FDC tablets — weight-band dosing

RHZE 150/75/400/275 mg (e.g. Akurit-4, Forecox)

30–37 kg: 2 tabs OD
38–54 kg: 3 tabs OD
55–70 kg: 4 tabs OD
>70 kg: 5 tabs OD

Continuation phase — RH 150/75 mg (e.g. Akurit)

Same weight-band tablet count as above, once daily

Pyridoxine (Vitamin B6)

25–50 mg/day with INH throughout — prevents peripheral neuropathy

Individual (non-FDC) tablet dosing by weight

Use when combined FDC tablets are unavailable — Thai formulary stock can be inconsistent.

Weight	INH 100mg tab	RIF 300mg cap	PZA 500mg tab	EMB 400mg tab
30–37 kg	1.5 (150mg)	1 (300mg)	1.5 (750mg)	1.5 (600mg)
38–54 kg	3 (300mg)	1.5 (450mg)	2.5 (1250mg)	2 (800mg)
55–70 kg	3 (300mg)	2 (600mg)	3 (1500mg)	3 (1200mg)
>70 kg	3 (300mg)	2 (600mg)	4 (2000mg)	4 (1600mg)

INH and RIF capped at 300mg/600mg respectively regardless of weight above 70kg. Round to nearest available split (most tabs are scored).

Monitoring timeline — Thai NTP Table 5.3

Test	Baseline	M1	M2	M3	M4	M5	M6
Clinical / weight	✓	✓	✓	✓	✓	✓	✓
AFB smear	✓	—	✓	if M2+	—	✓	✓
Molecular test (Xpert)	✓ dx+DST	—	if AFB+, no baseline DST	—	—	if AFB+	—
Culture ± DST	consider	—	if AFB+	—	—	if AFB+	—
CXR	✓	—	✓	—	—	—	✓
HIV test	✓	once only
LFT	✓*	only if symptomatic, or per risk-factor schedule*
BUN/Cr	✓**	—
Vision test	✓***	ongoing if risk factor / E >2 months

*Hepatitis risk factors: age >60, chronic alcohol use, prior liver disease/viral hepatitis, HIV, malnutrition, pregnancy — check AST/ALT/total bilirubin q1–2 weeks in month 1, then as appropriate. No risk factors → LFT only if symptomatic. **Renal risk (CKD, diabetic nephropathy, elderly, aminoglycoside use). ***Elderly or pre-existing visual impairment.

Outcome definitions

Culture positive at month 5+ → treatment failure → refer for DST-guided second-line therapy
"Cured" requires bacteriologic (culture) confirmation negative; without culture confirmation → "treatment completed" only
CT progression despite negative smear at completion → do not close as cured; repeat culture/DST, consider NTM/fungal/malignancy work-up
Poor responders (large cavitary disease, or AFB smear/culture still positive at month 2–3 with no DST resistance) → continuation phase may be extended 4→7 months, individualized with specialist input

Thai NTP action thresholds: Total bilirubin >3 mg/dL with normal/≤3× AST/ALT → stop R only. AST/ALT <5× ULN → continue, recheck LFT weekly. AST/ALT ≥5× ULN (asymptomatic), or ≥3× ULN with nausea/vomiting → stop H, R, Z (may bridge with E, Levofloxacin, Amikacin). Fulminant hepatitis → that drug class permanently contraindicated.

Rechallenge pathway — Thai NTP 2021

1 · AST/ALT <2× ULN AND total bilirubin <1.5 mg/dL

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2 · Add Isoniazid — start at full normal dose

↓ 1 week, check AST/ALT + bilirubin

3 · If normal → add Rifampicin — full dose

↓ 1 week, check AST/ALT + bilirubin

LFT stableAdd Pyrazinamide — full dose

LFT rises on any drugStop that drug immediately, never rechallenge it again

Important — order differs by guideline: Thai NTP 2021 sequences H → R → Z, each started at full dose with weekly LFT checks. ATS/CDC 2006 sequences R → H → Z (rifampicin first, least hepatotoxic) with graded dose escalation. Follow the Thai NTP order/dosing at Songklanagarind; ATS/CDC is the fallback only where Thai guidance is silent (e.g. PZA-free regimen choice).

Consider NAT2 acetylator genotype testing (if available) after a hepatitis episode, to guide safe INH dosing going forward.

Common side effects by drug

Drug	Common SE	Red flag
Isoniazid	Peripheral neuropathy, mild transaminitis, drowsiness	Numbness/tingling hands/feet
Rifampicin	Orange-red secretions (harmless), GI upset, flu-like reaction, CYP450 induction	Bleeding/bruising (thrombocytopenia, esp. intermittent/rechallenge dosing)
Pyrazinamide	Arthralgia (hyperuricemia), GI upset	Most hepatotoxic — jaundice, dark urine, RUQ pain
Ethambutol	Dose-dependent optic neuritis	Blurred vision, red-green color loss → stop EMB immediately

Other red flags (any drug): jaundice/pale stool/dark urine, rash with mucosal involvement or blistering (SJS/TEN — stop all drugs), confusion/coagulopathy (hepatic failure — emergency).

PZA-free regimen — IREL

Isoniazid + Rifampicin + Ethambutol + Levofloxacin

INH 4–6 mg/kg · RIF 8–12 mg/kg · EMB 15–20 mg/kg · Levofloxacin 750–1000 mg/day (10–15 mg/kg)

Total duration extended to 9 months (vs standard 6) — PZA's sterilizing activity is lost
Once RIF/INH individually confirmed tolerated, EMB + Levofloxacin can be added together — neither is a classic hepatotoxin, no need for staggered introduction
Levofloxacin: empty stomach — separate from dairy/antacids/divalent cations by ≥2h before / 4–6h after

Mono / polydrug-resistant TB — Thai NTP Table 6.2

Resistance	Regimen	Duration	Note
H	6RZE + FQ	6 mo	If FQ-susceptible
H (FQ-R/unsure)	6RZE	6 mo	No FQ if resistant/unknown
Z	2HRE / 7HR	9 mo	Thai-guideline PZA-substitute regimen — no fluoroquinolone needed
E	2HRZ / 4HR	6 mo	Standard regimen unaffected
H+Z	9–12 R + E + FQ	9–12 mo	—
H+E	6–9 RZ + FQ	6–9 mo	—
H+E+Z	2–3 AG+R+FQ+Eto / 10 R+FQ+Eto	12 mo	AG = aminoglycoside
R (mono)	MDR regimen	9–11 mo (shorter Bdq) or ≥18 mo (individualized)	Treat as MDR pathway

Relevant to hepatotoxicity-driven PZA discontinuation: the Thai NTP's own Z-resistant regimen (2HRE/7HR, 9 months) is a fluoroquinolone-free alternative to IREL when PZA is dropped for intolerance rather than confirmed resistance — worth flagging to the team even where the chosen regimen is IREL.

Resistance-guided regimens

RIF-resistant / MDR-TB (resistant to ≥ RIF+INH)

WHO-preferred all-oral shorter regimen: BPaLM — Bedaquiline + Pretomanid + Linezolid + Moxifloxacin, 6 months
Or longer individualized regimen based on full DST
Refer to MDR-TB treatment center

Pre-XDR / XDR-TB

Additional fluoroquinolone ± Group A drug resistance
Individualized regimen per DST — ID/pulmonology specialist required

Shorter all-oral Bdq-containing MDR/RR-TB regimen dosing — Thai NTP Table 6.3

Drug	30–35kg	36–45kg	46–55kg	56–70kg	>70kg
Bedaquiline	400mg/day ×2wk, then 200mg 3×/wk ×22wk (no weight-band dosing)
Levofloxacin	750 mg/day (no weight-band dosing)
Moxifloxacin	400 mg/day (no weight-band dosing)
Prothionamide/Ethionamide	500	500	750	750	1000
Clofazimine	100 mg/day (no weight-band dosing)
Pyrazinamide	1,000	1,000	1,500	1,500	2,000
Isoniazid (high-dose)	400	400	600	600	600
Ethambutol	800	800	1,200	1,200	1,200

Doses in mg/day. Adjust per adverse effects. Refer to regional/national MDR-TB expert panel for individualized longer regimens.