What are the NTP (National Tuberculosis Program) guidelines for treating pulmonary tuberculosis (PTB)?

NTEP Guidelines for Pulmonary Tuberculosis

For drug-susceptible pulmonary tuberculosis, treat with a 6-month regimen consisting of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) daily for 2 months, followed by isoniazid and rifampin (HR) daily for 4 months. 1, 2

Standard Treatment Regimen for Drug-Susceptible PTB

Intensive Phase (First 2 Months)

• Administer four drugs daily: Isoniazid (H), Rifampin (R), Pyrazinamide (Z), and Ethambutol (E) 3, 1, 2
• Ethambutol can be discontinued once drug susceptibility testing confirms full susceptibility to isoniazid and rifampin, particularly when community isoniazid resistance is <4% 2, 4
• This four-drug approach is effective even when the organism is resistant to isoniazid alone 4

Continuation Phase (Months 3-6)

• Continue Isoniazid and Rifampin daily for 4 months after completing the intensive phase 1, 2
• Total treatment duration is 6 months for most cases of pulmonary tuberculosis 3, 1

Dosing Specifications

• Rifampin dosing: Adults <50 kg receive 450 mg daily; adults ≥50 kg receive 600 mg daily 2
• Pyridoxine (Vitamin B6) 25-50 mg daily should be given to all HIV-infected patients receiving isoniazid to prevent neurologic side effects 1

Directly Observed Therapy (DOT)

All patients with tuberculosis should be treated with directly observed therapy (DOT), where medication ingestion is directly observed by a healthcare worker. 3, 1

• DOT is the preferred approach over self-administered therapy for all forms of tuberculosis 1
• Nonadherence is the main reason for treatment failure and development of drug-resistant strains 3
• Rates of drug-resistant TB and relapse are decreased in communities where DOT is used 3
• If universal DOT is not feasible, prioritize high-risk patients: those with drug-resistant disease, injection drug users, alcoholics, and homeless persons 3

Special Populations

HIV-Infected Patients

• Use the same 6-month standard regimen (2 months HRZE, 4 months HR) for HIV-infected patients receiving antiretroviral therapy 1, 2
• For HIV-infected patients NOT receiving ART, extend the continuation phase to 7 months (total 9 months of therapy) 2
• HIV testing is recommended for all patients with newly diagnosed tuberculosis 3, 1
• Rifampin may interact with protease inhibitors and non-nucleoside reverse transcriptase inhibitors, potentially requiring alteration of the anti-TB regimen 3

Pregnant Women

• Use the standard regimen: Rifampin, isoniazid, ethambutol, and pyrazinamide can all be used during pregnancy 2
• Streptomycin should be avoided due to ototoxicity to the fetus 5
• Prophylactic pyridoxine 10 mg/day is recommended along with anti-TB treatment 5

Patients with Diabetes Mellitus

• The drug regimen is the same as in non-diabetic patients 5
• Strict control of blood glucose is mandatory 5
• Doses of oral hypoglycemic agents may need to be increased due to interaction with rifampin 5
• Prophylactic pyridoxine is indicated 5

Patients with Renal Failure

• In mild renal failure with normal liver functions, use the standard regimen 5
• Dosages may require adjustment according to creatinine clearance, especially for streptomycin, ethambutol, and isoniazid 5

Patients with Pre-existing Liver Disease

• In stable disease with normal liver enzymes, all anti-tuberculous drugs may be used 5
• Frequent monitoring of liver function tests is required 5

Extended Treatment Indications

Patients with miliary, meningeal, or bone and joint tuberculosis require longer therapy beyond 6 months. 3

• Children with miliary tuberculosis, bone/joint tuberculosis, or tuberculous meningitis should receive a minimum of 12 months of therapy 4

Drug-Resistant Tuberculosis

Isoniazid-Resistant TB

• Treat with 6 months of rifampin, ethambutol, and pyrazinamide 3
• If isoniazid resistance is demonstrated during a 9-month regimen, continue rifampin and ethambutol for a minimum of 12 months 4

Multidrug-Resistant TB (MDR-TB)

• MDR-TB (resistance to at least isoniazid and rifampin) requires at least 18-24 months of therapy 3
• Use a regimen containing at least 5 drugs in the intensive phase and 4 drugs in the continuation phase 1
• The shorter 6-month all-oral bedaquiline-containing regimen (BPaLM: Bedaquiline, pretomanid, linezolid, and moxifloxacin) may be used for eligible MDR-TB patients 2
• Expert consultation is strongly recommended for all MDR-TB cases 3, 1

Monitoring and Safety

Clinical Monitoring

• Monitor liver function, especially during the first 2 months, due to the risk of hepatotoxicity 1, 2
• Perform monthly assessments of weight, adherence, symptom improvement, and side effects 1
• Follow-up with sputum smear microscopy and culture for pulmonary TB 2
• Monitor for QTc prolongation with bedaquiline, delamanid, and fluoroquinolones 2

Treatment Interruptions

• If treatment is interrupted for less than 14 days, continue treatment to complete the planned total dose 1
• If treatment is interrupted for 14 days or more, restart treatment from the beginning 1
• Despite gaps in therapy, 90% of patients should complete the 6-month regimen within 7 months 3

Public Health Reporting

All cases of tuberculosis should be reported immediately to the local public health department. 3, 1

• Prompt notification allows for contact and source case investigations 3
• Reporting enables monitoring of adherence to therapy and identification of infected contacts 3
• Report suspected cases based on clinical diagnosis or presence of acid-fast bacilli before definitive culture confirmation 3

Common Pitfalls to Avoid

• Do not confuse rifampin and rifapentine - they are not interchangeable medications 3
• Do not use 2 months of rifampin plus pyrazinamide for any indication due to severe hepatotoxicity risk 3
• Do not assume patient adherence - clinicians are poor predictors of which patients will adhere to therapy 3
• Do not use rifampin-containing regimens in post-renal transplant patients as rifampin increases clearance of cyclosporin 5