Highlights from the 2016 Treatment of Drug-Susceptible Tuberculosis Guidelines

This document contains key highlights from the Official American Thoracic Society (ATS)/Centers for Disease Control and Prevention (CDC)/Infectious Diseases Society of America (IDSA) Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis. The guidelines update previous ATS/CDC/ISDA guidelines published in Morbidity and Mortality Weekly Report in 2003.

About the Guidelines

• The guidelines provide recommendations on the clinical and public health management of tuberculosis (TB) in children and adults in well-resourced settings.
• The guidelines provide evidence-based recommendations that have been developed using GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology. GRADE involves structured literature review, systematic reviews and meta-analyses of combined data, and expert discussion to assess the certainty in the evidence and determine the strength of each recommendation.

Objectives of Antituberculosis Therapy

• The treatment of TB is centered on curing the individual patient and decreasing the transmission of TB bacteria to other people.
• The objectives of TB therapy are:
  1. Cure the individual patient and minimize risk of death and disability;
  2. Reduce transmission of M. tuberculosis to other persons; and
  3. Prevent the development of drug resistance during therapy.

Key Considerations When Developing a Case Management Plan

• Use case management interventions during treatment of patients with TB disease. Case management is defined as patient education and counseling, field and home visits, integration and coordination of care with specialists and medical home care, patient reminders, and incentives and enablers. (Recommendation 1)
• Use directly observed therapy (DOT) for treatment of patients with all forms of TB disease. (Recommendation 2)

Recommended Treatment Regimens

• The preferred regimen for treating adults with TB remains a regimen consisting of an intensive phase of 2 months of isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB) followed by a continuation phase of 4 months of INH and RIF. (See table 2 for more information on drug regimens.)
• Use the following practices for treatment of drug-susceptible pulmonary TB during the intensive phase (Recommendation 3):
  • Daily dosing, rather than intermittent dosing, is preferred.
  • If intermittent therapy is needed, use treatment three times per week for patients with:
    1. Low risk of relapse (i.e. drug-susceptible TB organisms, that at the start of treatment is non-cavitary and/or smear negative) and
    2. Negative HIV-infection test result (not HIV-infected).
  • If it is difficult to treat daily or three times per week, the use of treatment two times per week after an initial two weeks of daily therapy may be considered for patients with:
    1. Low risk of relapse (i.e. drug-susceptible TB organisms, that at the start of treatment is non-cavitary and/or smear negative) and
    2. Negative HIV-infection test result (not HIV-infected).
• Use the following practices for treatment of drug-susceptible pulmonary TB during the continuation phase (Recommendation 4):
  • Daily dosing or treatment three times per week is recommended.
  • If intermittent therapy is needed, treatment three times per week is preferred.
• Avoid generally the once weekly regimen of INH 900/RPT 600.
  • This regimen may be considered in uncommon situations where more than once weekly DOT is difficult to achieve.
  • When employed, the once weekly INH 900 mg plus RPT 600 mg regimen should be used only in HIV uninfected patients without cavitation on chest radiography and who are smear negative at 8 weeks.

Treatment in Special Situations

• The current guidelines provide recommendations on the management of TB in other special situations as well, such as extrapulmonary TB, culture-negative pulmonary TB, and TB during pregnancy and breastfeeding, among others.
• A key highlight in the current guidelines are the recommendations on the duration of the timing of HIV and TB therapy for patients living with HIV.
  • Patients co-infected with HIV who receive antiretroviral therapy (ART) should receive the following TB treatment regimen (Recommendation 5):
    1. 6 month daily regimen for drug susceptible pulmonary TB
       • Intensive Phase: 2 months of INH, RIF, PZA and EMB
       • Continuation Phase: 4 months INH and RIF
  • ART should be initiated during TB treatment (Recommendation 6):
    2. Ideally, ART should be initiated within the first two weeks of TB treatment with CD4 cell counts <50/mm3and by 8-12 weeks of TB treatment for patients with CD4 cell counts > 50/mm; however patients with TB meningitis SHOULD NOT start ART before 8-10 weeks of TB treatment is completed, regardless of CD4 count.
  • Four month treatment regimen is adequate for the treatment of adult patients who are not infected with HIV and who have AFB smear- and culture-negative pulmonary TB (Recommendation 9).
• Recommendations for the treatment of patients with TB meningitis and TB pericarditis are also provided in the guidelines.
  • Initial adjunctive corticosteroid therapy with dexamethasone should be given for six weeks for patients with TB meningitis (Recommendation 8).
  • Initial adjunctive corticosteroid therapy should not be routinely used in but should be reserved for selected patients with TB pericarditis (Recommendation 7).