What is the recommended drug regimen under the Revised National Tuberculosis Control Programme (RNTCP) for an adult patient with newly diagnosed pulmonary tuberculosis (TB), including those with a history of previous TB treatment or exposure to TB, and potential comorbidities such as impaired renal function or human immunodeficiency virus (HIV) co-infection?

RNTCP Drug Recommendations for Tuberculosis

Standard First-Line Regimen for New Pulmonary TB Cases

The Revised National Tuberculosis Control Programme (RNTCP) recommends a 6-month regimen consisting of isoniazid (H), rifampicin (R), pyrazinamide (Z), and ethambutol (E) for 2 months (intensive phase), followed by isoniazid and rifampicin for 4 months (continuation phase), administered as directly observed therapy (DOT) three times weekly. 1, 2

Intensive Phase (2 Months)

• Administer isoniazid, rifampicin, pyrazinamide, and ethambutol three times weekly under direct observation 3
• Dosing for adults: Isoniazid 15 mg/kg (max 900 mg), Rifampicin 10 mg/kg (max 600 mg), Pyrazinamide 50-70 mg/kg, Ethambutol 30 mg/kg three times weekly 3, 4
• The fourth drug (ethambutol) prevents emergence of resistance while awaiting drug susceptibility testing results 3, 2

Continuation Phase (4 Months)

• Continue isoniazid and rifampicin three times weekly for an additional 4 months 3, 1
• Dosing: Isoniazid 15 mg/kg (max 900 mg), Rifampicin 10 mg/kg (max 600 mg) three times weekly 3

Critical Implementation Points

• All intermittent (twice or three times weekly) regimens must be given by directly observed therapy (DOT) to ensure adherence and prevent drug resistance 3, 1, 2
• If drug susceptibility testing confirms full susceptibility after 2 months, ethambutol can be discontinued 3, 2
• If cultures remain positive at 2 months or cavitation is present on initial chest radiograph, extend the continuation phase to 7 months (total 9 months) 3

Special Populations and Modifications

Previously Treated TB Cases

• Do not use the standard retreatment regimen (2SHRZE/1HRZE/5HRE) as it is no longer recommended 5
• Perform drug susceptibility testing (DST) immediately, including GeneXpert MTB/RIF to detect rifampicin resistance 5, 6
• If rifampicin resistance is excluded but isoniazid DST unavailable, use the standard 6-month regimen (2HRZE/4HR) 5
• If isoniazid resistance is confirmed with rifampicin susceptibility, use rifampicin, ethambutol, pyrazinamide, and levofloxacin for 6 months 5

HIV Co-Infection

• Use the same 6-month four-drug regimen (2HRZE/4HR) but monitor clinical and bacteriologic response closely 2, 6
• If CD4 count <100 cells/mm³, cavitation present, or cultures positive at 2 months, extend treatment to 9 months 7
• Rifabutin should replace rifampicin if the patient is on protease inhibitors or NNRTIs to avoid critical drug interactions 7
• Continue antiretroviral therapy without interruption; stopping ART increases mortality risk 7
• Administer pyridoxine 25-50 mg daily to prevent peripheral neuropathy 7, 6

Impaired Renal Function

• Adjust doses of streptomycin, ethambutol, and isoniazid based on creatinine clearance 6
• Rifampicin and pyrazinamide do not require dose adjustment 6
• In hemodialysis patients, administer ethambutol 8 hours before dialysis 6
• Avoid streptomycin in severe renal impairment due to nephrotoxicity risk 8

Pre-Existing Liver Disease

• If liver enzymes are normal despite chronic liver disease, use the standard regimen with frequent monitoring (liver function tests twice weekly for 2 weeks, then every 2 weeks for 2 months, then monthly) 8, 6
• If baseline transaminases >3× upper limit of normal, avoid pyrazinamide and use a 9-month regimen of isoniazid, rifampicin, and ethambutol 1, 8
• Stop all hepatotoxic drugs (isoniazid, rifampicin, pyrazinamide) immediately if transaminases rise >5× normal or bilirubin increases 9, 8
• After normalization, reintroduce drugs sequentially: isoniazid first, then rifampicin, but do not reintroduce pyrazinamide due to poor prognosis of recurrent pyrazinamide hepatitis 9, 8

Pregnancy and Lactation

• Use the standard 6-month regimen (2HRZE/4HR) as all these drugs are safe in pregnancy 1, 6
• Avoid streptomycin due to fetal ototoxicity 1, 6
• Administer pyridoxine 10 mg daily prophylactically 6

Diabetes Mellitus

• Use the standard regimen but ensure strict glycemic control 6
• Increase oral hypoglycemic doses as rifampicin induces their metabolism 6
• Administer prophylactic pyridoxine 6

CNS and Extrapulmonary Tuberculosis

Tuberculous Meningitis

• Extend treatment duration to 12 months: 2 months intensive phase (HRZE) followed by 10 months continuation phase (HR) 3, 1
• Administer adjunctive corticosteroids early in the course to decrease neurologic sequelae 1
• Children with miliary TB, bone/joint TB, or meningitis require minimum 12 months therapy 1, 2

Other Extrapulmonary Sites

• Use the standard 6-month regimen for peripheral lymph nodes, bone/joint (except spine in children), pericarditis, and pleural effusion 3, 1
• Adjunctive corticosteroids prevent cardiac constriction in tuberculous pericarditis 1

Critical Pitfalls to Avoid

• Never use rifampicin with protease inhibitors or NNRTIs without switching to rifabutin, as this causes treatment failure of either HIV or TB 7
• Never add a single drug to a failing regimen; this creates acquired resistance 5, 6
• Never use daily self-administered intermittent therapy; all intermittent regimens require DOT 3, 1
• Never reintroduce pyrazinamide after drug-induced hepatitis due to high risk of fulminant hepatic failure 8
• Never delay TB treatment to accommodate other medications; TB treatment is the immediate priority for mortality reduction 10
• Never omit ethambutol in the initial phase unless drug susceptibility is confirmed and isoniazid resistance is <4% in the community 3, 2