Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis

Abstract

The American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America jointly sponsored the development of this guideline for the treatment of drug-susceptible tuberculosis, which is also endorsed by the European Respiratory Society and the US National Tuberculosis Controllers Association. Representatives from the American Academy of Pediatrics, the Canadian Thoracic Society, the International Union Against Tuberculosis and Lung Disease, and the World Health Organization also participated in the development of the guideline. This guideline provides recommendations on the clinical and public health management of tuberculosis in children and adults in settings in which mycobacterial cultures, molecular and phenotypic drug susceptibility tests, and radiographic studies, among other diagnostic tools, are available on a routine basis. For all recommendations, literature reviews were performed, followed by discussion by an expert committee according to the Grading of Recommendations, Assessment, Development and Evaluation methodology. Given the public health implications of prompt diagnosis and effective management of tuberculosis, empiric multidrug treatment is initiated in almost all situations in which active tuberculosis is suspected. Additional characteristics such as presence of comorbidities, severity of disease, and response to treatment influence management decisions. Specific recommendations on the use of case management strategies (including directly observed therapy), regimen and dosing selection in adults and children (daily vs intermittent), treatment of tuberculosis in the presence of HIV infection (duration of tuberculosis treatment and timing of initiation of antiretroviral therapy), as well as treatment of extrapulmonary disease (central nervous system, pericardial among other sites) are provided. The development of more potent and better-tolerated drug regimens, optimization of drug exposure for the component drugs, optimal management of tuberculosis in special populations, identification of accurate biomarkers of treatment effect, and the assessment of new strategies for implementing regimens in the field remain key priority areas for research. See the full-text online version of the document for detailed discussion of the management of tuberculosis and recommendations for practice.

Keywords: HIV infections; Mycobacterium tuberculosis; antitubercular agents; case management; public health.

Figure 1.

Factors to be considered in deciding to initiate treatment empirically for active tuberculosis (TB) (prior to microbiologic confirmation). Abbreviations: AFB, acid-fast bacilli; HIV, human immunodeficiency virus; IGRA, interferon-γ release assay; Mtb, Mycobacterium tuberculosis; TNF, tumor necrosis factor; TST, tuberculin skin test.

Figure 2.

Baseline and follow-up evaluations for patients treated with first-line tuberculosis medications. Shading around boxes indicates activities that are optional or contingent on other information. ¹Obtain sputa for smear and culture at baseline, then monthly until 2 consecutive specimens are negative. Collecting sputa more often early in treatment for assessment of treatment response and at end of treatment is optional. At least one baseline specimen should be tested using a rapid molecular test. ²Drug susceptibility for isoniazid, rifampin, ethambutol (EMB), and pyrazinamide should be obtained. Repeat drug susceptibility testing if patient remains culture positive after completing 3 months of treatment. Molecular resistance testing should be performed for patients with risk for drug resistance. ³Obtain chest radiograph at baseline for all patients, and also at month 2 if baseline cultures are negative. End-of-treatment chest radiograph is optional. Other imaging for monitoring of extrapulmonary disease. ⁴Monitor weight monthly to assess response to treatment; adjust medication dose if needed. ⁵Assess adherence and monitor improvement in tuberculosis symptoms (eg, cough, fever, fatigue, night sweats) as well as development of medication adverse effects (eg, jaundice, dark urine, nausea, vomiting, abdominal pain, fever, rash, anorexia, malaise, neuropathy, arthralgias). ⁶Patients on EMB: baseline visual acuity (Snellen test) and color discrimination tests, followed by monthly inquiry about visual disturbance and monthly color discrimination tests. ⁷Liver function tests only at baseline unless there were abnormalities at baseline, symptoms consistent with hepatotoxicity develop, or for patients who chronically consume alcohol, take other potentially hepatotoxic medications, or have viral hepatitis or history of liver disease, human immunodeficiency virus (HIV) infection, or prior drug-induced liver injury. ⁸Baseline for all patients. Further monitoring if there are baseline abnormalities or as clinically indicated. ⁹HIV testing in all patients. CD4 lymphocyte count and HIV RNA load if positive. ¹⁰Patients with hepatitis B or C risk factor (eg, injection drug use, birth in Asia or Africa, or HIV infection) should have screening tests for these viruses. ¹¹Fasting glucose or hemoglobin A1c for patients with risk factors for diabetes according to the American Diabetes Association including: age >45 years, body mass index >25 kg/m², first-degree relative with diabetes, and race/ethnicity of African American, Asian, Hispanic, American Indian/Alaska Native, or Hawaiian Native/Pacific Islander. Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase.