Guideline Summary for Management of Pulmonary Tuberculosis Relapse

Initial Assessment and Diagnostic Testing

Obtain sputum specimens immediately for acid‑fast bacilli smear, culture, and drug‑susceptibility testing (first‑ and second‑line agents) before initiating therapy. 4
Perform rapid molecular testing for rifampin and isoniazid resistance at diagnosis; if rifampin resistance is identified, promptly assess fluoroquinolone and second‑line drug susceptibility. 5
Do not add a single drug to a failing regimen, as this promotes acquisition of resistance. 4

Apply the WHO Category II retreatment regimen (2 months SHRZE / 1 month HRZE / 5 months HRE; total 8 months). This 5‑drug intensive phase for the first 3 months ensures at least three active agents, reducing the risk of selecting resistant bacilli. 1
Recommended daily dosages for retreatment: isoniazid ≈ 5 mg/kg, rifampin ≈ 10 mg/kg, pyrazinamide ≈ 25 mg/kg, streptomycin ≈ 15 mg/kg, ethambutol ≈ 15 mg/kg. 2

Assume possible drug resistance and start an expanded regimen containing ≥ 5–6 drugs. Include isoniazid, rifampin, pyrazinamide, a fluoroquinolone (e.g., levofloxacin, moxifloxacin, or gatifloxacin), and an injectable agent (streptomycin if not previously used and susceptible, or amikacin/kanamycin/capreomycin). 4
Consider adding a second oral agent such as cycloserine, ethionamide, or PAS to further strengthen the regimen. 4

MDR‑TB is defined as resistance to at least rifampin and isoniazid. 5
Refer the patient immediately to a specialized TB treatment center or obtain expert consultation. 4
Construct an individualized regimen with ≥ 5 effective drugs during the intensive phase (5–7 months after culture conversion) and ≥ 4 effective drugs during the continuation phase; total treatment duration should be 15–21 months after culture conversion. 5

Group	Recommended Drugs (use if susceptibility confirmed)
A (core)	Later‑generation fluoroquinolone (levofloxacin or moxifloxacin) ; bedaquiline
B (add one)	Linezolid (600 mg dosing reduces adverse events) ; clofazimine
C (add ≥ 2 to reach ≥ 5 drugs)	Cycloserine/terizidone ; Ethambutol (if susceptible) ; Pyrazinamide (if susceptible) ; Ethionamide/Prothionamide

All Group A–C recommendations are based on WHO guidance and supported by recent evidence. 6

Use the 6‑month BPaLM regimen (bedaquiline + pretomanid + linezolid 600 mg + moxifloxacin) for adolescents ≥ 14 years and adults, provided there has been ≤ 1 month prior exposure to second‑line drugs, no fluoroquinolone resistance, and limited disease extent. 7
This regimen achieves an estimated 90–100 % treatment‑success rate. 5

Perform monthly sputum cultures throughout therapy to assess bacteriologic response. 8
After 3 months of multidrug therapy, 90–95 % of patients should have converted to culture‑negative status and show clinical improvement. 4
Define treatment failure as a positive culture after 4 months of appropriate therapy. 4
In cases of cavitary disease with a positive culture at 2 months, extend the continuation phase to 7 months (total 9 months of treatment). 8

Implement directly observed therapy (DOT) for the entire duration of retreatment in all patients. 1
Prefer fixed‑dose combination (FDC) tablets to minimize the risk of selecting resistant mutants and to improve adherence. 1
In settings where > 2 % of isolates exhibit single‑drug resistance, prescribe ≥ 4 drugs for new cases and ≥ 5 drugs for retreatment cases. 1

Do not use intermittent (twice‑ or thrice‑weekly) regimens in HIV‑infected patients or those with cavitary disease, as this leads to high relapse rates and acquired resistance. 8
Do not commence empirical retreatment without first obtaining sputum specimens for culture and DST; this practice promotes further resistance. 5
Do not assume drug susceptibility based solely on prior treatment history; always confirm with current DST. 4
Do not delay specialist consultation when treatment failure or confirmed drug resistance is identified. 4