What are the latest guidelines for treating tuberculosis (TB)?

Latest Tuberculosis Treatment Guidelines

The current standard treatment for drug-susceptible tuberculosis consists of a 2-month intensive phase with isoniazid, rifampicin, pyrazinamide, and ethambutol followed by a 4-month continuation phase with isoniazid and rifampicin (2HRZE/4HR), with daily dosing strongly recommended over intermittent dosing. 1

Drug-Susceptible TB Treatment

First-Line Regimen

• Intensive phase (2 months): Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), and Ethambutol (E)
• Continuation phase (4 months): Isoniazid (H) and Rifampicin (R)
• Daily dosing is strongly recommended 1
• Fixed-dose combinations may provide a more convenient form of drug administration 1

Dosing

• Adults: Isoniazid 5 mg/kg (up to 300 mg) daily; Rifampicin 10 mg/kg (up to 600 mg) daily 2, 3
• Children: Isoniazid 10-15 mg/kg (up to 300 mg) daily; Rifampicin 10-20 mg/kg (up to 600 mg) daily 2, 3

Latent TB Infection (LTBI) Treatment

Preferred Regimens (in order of preference) 1:

1. 3 months of once-weekly isoniazid plus rifapentine
2. 4 months of daily rifampin
3. 3 months of daily isoniazid plus rifampin

Alternative Regimens:

• Daily isoniazid for 6 or 9 months (higher toxicity risk and lower completion rates) 1

Drug-Resistant TB Treatment

Isoniazid-Resistant TB

• Rifampicin, ethambutol, pyrazinamide, and levofloxacin for 6 months 1
• Streptomycin or other injectable agents are not recommended 1

MDR/RR-TB Treatment

For MDR/RR-TB (multidrug-resistant/rifampicin-resistant TB), the following medications are recommended for longer regimens 1:

• Group A drugs (include all when possible):

  • Bedaquiline (strongly recommended for patients ≥18 years)
  • Levofloxacin or moxifloxacin
  • Linezolid

• Group B drugs (add one or both if needed):

  • Clofazimine
  • Cycloserine or terizidone

• Group C drugs (add to complete regimen when Group A and B cannot be used):

  • Ethambutol
  • Delamanid
  • Pyrazinamide
  • Other agents based on susceptibility

• Kanamycin and capreomycin should not be included in MDR/RR-TB regimens 1

Patient-Centered Approach

A patient-centered approach is essential for successful treatment 1:

• Directly observed therapy (DOT) or video-observed therapy (VOT) should be considered to ensure adherence
• Treatment supporters who are acceptable to the patient may be identified
• Financial, social, and psychosocial support may enhance treatment adherence
• Regular monitoring for adverse effects and treatment response is crucial

Special Populations

Pregnant Women

• Streptomycin should be avoided due to risk of congenital deafness
• Pyrazinamide is generally not recommended in the US due to inadequate teratogenicity data
• Initial treatment should consist of isoniazid and rifampin, with ethambutol added if isoniazid resistance is possible 2
• Prophylactic pyridoxine (10mg/day) is recommended 2

HIV Co-infection

• Same regimen as HIV-negative patients, but careful monitoring of clinical and bacteriologic response is essential
• If response is slow or suboptimal, therapy should be prolonged
• Drug interactions between rifampin and antiretroviral medications require careful management 4

Treatment Monitoring

• Regular clinical evaluations to assess response and monitor for adverse effects
• Monthly monitoring for hepatotoxicity, optic neuritis, and peripheral neuropathy
• Sputum cultures should be obtained to document conversion to negative
• Treatment failure is defined as continued or recurrently positive cultures after 4 months of treatment

Common Pitfalls and Caveats

1. Drug resistance development: Failure to ensure adherence is the main reason for treatment failure and development of drug-resistant strains. Always consider DOT for patients at risk of non-adherence.

2. Rifampicin vs. Rifapentine confusion: These drugs are not interchangeable. Ensure patients receive the correct medication for the intended regimen 1.

3. Inadequate initial regimen: Ethambutol should be included in the initial regimen until susceptibility results are available, unless there is little possibility of drug resistance (less than 4% primary resistance to isoniazid in the community) 1.

4. Drug interactions: Rifampicin induces metabolism of many drugs including oral contraceptives, warfarin, and antiretrovirals. Always check for potential interactions.

5. Inadequate monitoring: Failure to monitor for adverse effects can lead to treatment discontinuation. Regular monitoring of liver function, vision (with ethambutol), and other potential side effects is essential.

By following these guidelines, TB treatment can achieve cure rates exceeding 95% in drug-susceptible cases when patients complete the full course of therapy.