Guideline sources The following summarized guidelines for the evaluation and management of pulmonary tuberculosis are prepared by our editorial team based on guidelines from the U.S. Preventive Services Task Force (USPSTF 2023), the World Health Organization (WHO 2022; 2021; 2020; 2017), the Center for Disease Control (CDC/NTCA 2020), the Infectious Diseases Society of America (IDSA/ERS/ATS/CDC 2019), the Infectious Diseases Society of America (IDSA/ATS/CDC 2017; 2016), and the American College of Radiology (ACR 2017). 1 2 3 4 5 6 7 8 9 10 Guidelines 1. Screening and diagnosis Screening for latent tuberculosis: As per USPSTF 2023 guidelines, obtain screening for latent tuberculosis infection in populations at increased risk. B As per WHO 2020 guidelines, obtain systematic testing for latent tuberculosis infection in patients initiating anti-TNF treatment, receiving dialysis, preparing for an organ or https://web.pathway.md/diseases/recEHAIr9AnzPn9ci 1/9 6/29/23, 11:37 PM Pulmonary tuberculosis Pathway hematological transplant, or having silicosis. E Show 3 more As per ATS 2017 guidelines, obtain an IGRA rather than a tuberculin skin test in 5 years old patients meeting the following criteria: likely to be infected with Mycobacterium tuberculosis low or intermediate risk of disease progression it has been decided that testing for latent tuberculosis infection is warranted history of BCG vaccination or it is expected that the individual is unlikely to return to have the TST read. A Show 4 more 2. Diagnostic investigations Chest imaging: Obtain CXR as first-line imaging in patients with suspected tuberculosis. Obtain CXR in patients with new evidence of exposure or at high risk for the development of tuberculosis, although it may be of low yield in patients with no clinical symptoms. B Obtain chest CT if CXR is nonrevealing or nondiagnostic. B Respiratory specimen collection: consider performing sputum induction rather than flexible bronchoscopic sampling as the initial respiratory sampling method in adult patients with suspected pulmonary tuberculosis if they are unable to expectorate sputum or the expectorated sputum is AFB smear microscopy negative. C Show 3 more Smear and culture: obtain AFB smear microscopy in all patients with pulmonary tuberculosis. A Show 2 more Nucleic acid amplification testing, initial testing: As per WHO 2021 guidelines, obtain Xpert MTB/RIF rather than smear microscopy/culture and phenotypic drug susceptibility testing as an initial diagnostic test for tuberculosis and rifampicin resistance detection in sputum in adult patients with signs and symptoms of pulmonary tuberculosis. B Show 6 more As per CDC/IDSA/ATS 2017 guidelines: Consider obtaining an NAAT (the Hologic Amplified Mycobacteria Tuberculosis Direct test or the Cepheid Xpert MTB/Rif test) on the initial respiratory specimen obtained from patients with suspected pulmonary tuberculosis. C Obtain rapid molecular drug susceptibility testing for rifampin, with or without isoniazid, on the respiratory specimens obtained from AFB smear- or NAAT (Hologic)-positive patients meeting one of the following criteria: have been treated for tuberculosis in the past were born in or have lived for at least 1 year in a foreign country with at least a moderate tuberculosis incidence ( 20 per 100, 000) or a high primary MDR-TB prevalence ( 2%) are contacts of patients with MDR-TB https://web.pathway.md/diseases/recEHAIr9AnzPn9ci 2/9 6/29/23, 11:37 PM Pulmonary tuberculosis Pathway are human immunodeficiency virus-infected. A Nucleic acid amplification testing (repeated testing): avoid obtaining repeated testing with Xpert Ultra in adult patients with signs and symptoms of pulmonary tuberculosis having an Xpert Ultra trace positive result on the initial test. D Show 4 more Genotyping: collect one culture isolate from each mycobacterial culture-positive patient and submit it to a regional genotyping laboratory for genotyping. B 3. Medical management Setting of care: As per WHO 2017 guidelines, consider offering the following treatment administration options in patients on tuberculosis treatment: community- or home-based directly observed treatment over health facility-based directly observed treatment or unsupervised treatment C directly observed treatment administered by trained lay providers or health-care workers over directly observed treatment administered by family members or unsupervised treatment C video-observed treatment over directly observed treatment when the video communication technology is available and can be appropriately organized and operated by healthcare providers and patients. C As per ATS 2016 guidelines, consider delivering directly observed treatment rather than self- administered therapy for routine treatment of patients with all forms of tuberculosis. C Management of latent tuberculosis: As per CDC 2020 guidelines: Administer any of the following regimens as the preferred treatment for latent tuberculosis: isoniazid plus rifapentine weekly for 3 months B rifampin daily for 4 months B isoniazid plus rifampin daily for 3 months in patients with B or without human immunodeficiencies virus infection. B Administer any of the following regimens as the alternative treatment for latent tuberculosis: isoniazid once daily for 6 months in patients with B or without human immunodeficiencies virus infection B isoniazid once daily for 9 months. B As per WHO 2020 guidelines: Administer any of the following regimens for the treatment of latent tuberculosis regardless of human immunodeficiency virus status: isoniazid daily for 6 or 9 months isoniazid plus rifapentine weekly for 3 months isoniazid plus rifampicin daily for 3 months. E Consider administering the following regimens as alternative options for latent tuberculosis: https://web.pathway.md/diseases/recEHAIr9AnzPn9ci 3/9 6/29/23, 11:37 PM Pulmonary tuberculosis Pathway isoniazid plus rifapentine for 1 month rifampicin daily for 4 months. E Management of drug-susceptible tuberculosis: As per WHO 2017 guidelines, administer the 6-month rifampicin-based regimen (2HRZE/4HR) rather than 4-month fluoroquinolone-containing regimens in patients with drug- susceptible pulmonary tuberculosis. B Show 3 more As per ATS 2016 guidelines, prescribe daily rather than intermittent dosing in the intensive phase of therapy in patients with drug-susceptible pulmonary tuberculosis. B Show 2 more Management of drug-resistant tuberculosis, isoniazid-resistant, rifampin-susceptible: As per WHO 2022 guidelines, administer a 6-month regimen of rifampicin, ethambutol, pyrazinamide, and levofloxacin for the treatment of patients with confirmed rifampicin- susceptible, isoniazid-resistant tuberculosis. Do not add streptomycin or other injectable agents to the treatment regimen. B As per IDSA/ERS/CDC/ATS 2019 guidelines, consider including pyrazinamide in the treatment regimen of patients with isoniazid-resistant tuberculosis if the Mycobacterium tuberculosis isolates have not been found resistant to pyrazinamide. C Show 2 more Management of drug-resistant tuberculosis, multidrug-resistant, choice of regimen: As per WHO 2022 guidelines, consider administering the 6-month regimen composed of bedaquiline, pretomanid, linezolid (600 mg), and moxifloxacin rather than the 9- or 18-month regimens in patients with MDR-TB/RR-TB and pre-XDR-TB. C Show 5 more As per IDSA/ERS/CDC/ATS 2019 guidelines, consider including at least 5 drugs in the intensive and 4 drugs in the continuation phases of treatment in patients with MDR-TB. C Show 5 more Management of drug-resistant tuberculosis, multidrug-resistant, duration of treatment: As per WHO 2022 guidelines, consider completing an intensive phase of 6-7 months in most patients with MDR-TB/RR-TB on longer regimens on longer regimens containing amikacin or streptomycin. Consider modifying duration according to the patient's response to therapy. C Show 2 more As per IDSA/ERS/CDC/ATS 2019 guidelines: Consider completing an intensive phase of 5-7 months after culture conversion in patients with MDR-TB. C Consider completing a total treatment duration of 15-21 months after culture conversion in patients with MDR-TB. C Management of drug-resistant tuberculosis (extensively drug-resistant): consider continuing treatment for a total duration of 15-24 months after culture conversion in patients with pre-extensively and XDR-TB. C Management of contacts: https://web.pathway.md/diseases/recEHAIr9AnzPn9ci 4/9 6/29/23, 11:37 PM Pulmonary tuberculosis Pathway As per WHO 2020 guidelines, consider excluding active tuberculosis before preventive treatment in human immunodeficiency virus-negative, 5 years old household contacts (and other risk groups) based on the absence of any symptoms of tuberculosis and the absence of abnormal chest radiographic findings. E Show 2 more As per ATS 2019 guidelines, consider initiating treatment for latent tuberculosis infection in contacts to patients with MDR-TB. C 4. Surgical interventions Pulmonary resection: As per WHO 2022 guidelines, consider performing elective partial lung resection (lobectomy or wedge resection) alongside a recommended MDR-TB treatment regimen in patients with rifampicin- or MDR-TB. C As per ATS 2019 guidelines, consider performing elective partial lung resection (lobectomy or wedge resection) in adult patients with MDR-TB receiving antimicrobial-based therapy. Avoid performing elective total lung resection (pneumonectomy). C 5. Specific circumstances Patients with culture-negative tuberculosis: consider administering a 4-month regimen for the treatment of human immunodeficiency virus-negative adult patients with AFB smear- and culture-negative pulmonary tuberculosis. C Patients with HIV infection, tuberculosis treatment: As per WHO 2017 guidelines, administer the 6-month standard treatment regimen over an extended treatment for 8 months in patients with drug-susceptible pulmonary tuberculosis and human immunodeficiency virus infection receiving antiretroviral therapy during tuberculosis treatment. B As per CDC/IDSA/ATS 2016 guidelines: Consider administering the standard 6-month daily regimen consisting of an intensive phase of 2 months of isoniazid, rifampin, pyrazinamide, and ethambutol followed by a continuation phase of 4 months of isoniazid and rifampin for the treatment of drug- susceptible pulmonary tuberculosis in human immunodeficiency virus-infected patients receiving antiretroviral therapy. C Consider extending the continuation phase with isoniazid and rifampin for an additional 3 months (a continuation phase of 7 months in duration, corresponding to a total of 9 months of therapy) for the treatment of drug-susceptible pulmonary tuberculosis human immunodeficiency virus-infected patients not receiving antiretroviral therapy during tuberculosis treatment. C Patients with HIV infection, antiretroviral therapy: As per WHO 2022 guidelines, initiate antiretroviral therapy as early as possible (within the first 8 weeks) following the initiation of antituberculosis treatment in all patients with human https://web.pathway.md/diseases/recEHAIr9AnzPn9ci 5/9 6/29/23, 11:37 PM Pulmonary tuberculosis Pathway immunodeficiency virus infection and drug-resistant tuberculosis requiring second-line antituberculosis drugs, irrespective of the CD4 cell count. B As per WHO 2017 guidelines, initiate antiretroviral therapy in all patients with tuberculosis and human immunodeficiency virus infection, regardless of the CD4 cell count. Initiate tuberculosis treatment first, followed by antiretroviral therapy as soon as possible within the first 8 weeks of treatment. A . Initiate antiretroviral therapy within the first 2 weeks of initiating tuberculosis treatment in human immunodeficiency virus infection-positive patients with profound immunosuppression, such as CD4 counts < 50 cells/mm . As per CDC/IDSA/ATS 2016 guidelines, initiate antiretroviral therapy during tuberculosis treatment in patients coinfected with human immunodeficiency virus, ideally starting within the first 2 weeks of tuberculosis treatment in patients with CD4 counts < 50 cells/ L and by 8-12 weeks of tuberculosis treatment in patients with CD4 counts 50 cells/ L. A Patients with HIV infection (preventive treatment): screen adult and adolescent patients with human immunodeficiency virus for tuberculosis according to a clinical algorithm. Initiate preventive treatment in patients not having any current symptoms of cough, fever, weight loss, or night sweats, regardless of their antiretroviral treatment status, as they are unlikely to have active tuberculosis. E Show 7 more 6. Patient education Patient support: As per WHO 2017 guidelines, provide health education and counseling on the disease and treatment adherence in patients receiving tuberculosis treatment. B Show 2 more As per ATS 2016 guidelines, consider offering case management interventions (such as patient education/counseling, field/home visits, integration/coordination of care with specialists and medical home, patient reminders, and incentives/enablers) in addition to curative interventions in patients with tuberculosis. C 7. Follow-up and surveillance Assessment of treatment response: obtain sputum culture in addition to sputum smear microscopy to monitor treatment response in patients with MDR-TB/RR-TB on longer regimens. Consider repeating sputum culture at monthly intervals. B Clinical findings Symptoms Past medical history Cough CKD Fatigue Diabetes mellitus Fever Human immunodeficiency virus infection Hemoptysis https://web.pathway.md/diseases/recEHAIr9AnzPn9ci 6/9 6/29/23, 11:37 PM Pulmonary tuberculosis Pathway Loss of appetite Immunocompromising condition Malaise Malignancy Night sweats Rheumatoid arthritis Weight loss SLE Silicosis Medication history Sj gren's disease Solid organ transplantation TNF-alpha antagonists Substance use disorder Anthropomorphic exam Social history Malnutrition Homelessness Hematological findings IV drug use Imprisonment Anemia Residing in nursing facilities Monocytosis Tobacco use WBC count blood eosinophils Lab findings blood leukocyte count IGRA Imaging findings urine lipoarabinomannan Atelectasis Microbiological findings Bronchiectasis sputum AFB Hilar lymphadenopathy sputum mycobacterial culture Pneumothorax Pulmonary cavity Diagnostic procedures Pulmonary fibrosis Pulmonary infiltrates tuberculin skin test Studies 2022 SHINE In children with non-severe, symptomatic, presumed drug-susceptible tuberculosis, 4 months treatment was noninferior to 6 months treatment with respect to treatment failure or disease recurrence at 72 weeks. Anna Turkova et al. N Engl J Med. 2022 Mar 10. 2018 Rifampin in latent TB In patients with latent tuberculosis infection, 4-month regimen of rifampin, as compared with 9- month regimen of isoniazid, was not inferior for the prevention of active tuberculosis. In rifampin group, among 3443 patients, confirmed active tuberculosis and clinically diagnosed active tuberculosis developed in 4 and 4 patients, respectively, during 7732 person-years of follow-up, as compared with 4 and 5 patients, respectively, among 3416 patients in the isoniazid group during 7652 person-years of follow-up. The rate differences (rifampin minus isoniazid) for confirmed active tuberculosis and for confirmed or clinically diagnosed tuberculosis were < 0.01 cases per 100 person-years (95% CI -0.14 to 0.16) and < 0.01 cases per 100 person-years (95% CI -0.23 to 0.22), respectively. The upper boundaries of the 95% CI for the rate differences https://web.pathway.md/diseases/recEHAIr9AnzPn9ci 7/9 6/29/23, 11:37 PM Pulmonary tuberculosis Pathway of the confirmed cases and for the confirmed or clinically diagnosed cases of tuberculosis were less than the prespecified noninferiority margin of 0.75% in cumulative incidence. The difference in the treatment-completion rates was 15.1% (95% CI 12.7-17.4). The rate differences for adverse events of grade 3-5 occurring within 146 days (120% of the 4-month planned duration of the rifampin regimen) for all events and hepatotoxic events were -1.1% (95% CI -1.9 to -0.4) and -1.2% (95% CI -1.7 to -0.7), respectively. Menzies D et al. N Engl J Med. 2018 Aug 2. Show 1 more References 1. Payam Nahid, Sundari R Mase, Giovanni Battista Migliori et al. Treatment of Drug-Resistant Tuberculosis. An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline. Am J Respir Crit Care Med. 2019 Nov 15;200 10):e93-e142. Open 2. No authors listed. Guidelines for treatment of drug-susceptible tuberculosis and patient care. Geneva: World Health Organization; 2017. Open 3. No authors listed. WHO consolidated guidelines on tuberculosis. Module 4 treatment - drug- resistant tuberculosis treatment, 2022 update. Geneva: World Health Organization; 2022. Open 4. No authors listed. WHO consolidated guidelines on tuberculosis: module 1 prevention: tuberculosis preventive treatment. Geneva: World Health Organization; 2020. Open 5. Payam Nahid, Susan E Dorman, Narges Alipanah et al. Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis. Clin Infect Dis. 2016 Oct 1;63 7):e147-e195. Open 6. No authors listed. WHO consolidated guidelines on tuberculosis: module 3 diagnosis: rapid diagnostics for tuberculosis detection, 2021 update. Geneva: World Health Organization; 2021. Open 7. David M Lewinsohn, Michael K Leonard, Philip A LoBue et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children. Clin Infect Dis. 2017 Jan 15;64 2 111 115. Open 8. US Preventive Services Task Force, Carol M Mangione, Michael J Barry et al. Screening for Latent Tuberculosis Infection in Adults: US Preventive Services Task Force Recommendation Statement. JAMA. 2023 May 2;329 17 1487 1494. Open 9. Expert Panel on Thoracic Imaging:, James G Ravenel, Jonathan H Chung et al. ACR Appropriateness Criteria Imaging of Possible Tuberculosis. J Am Coll Radiol. 2017 May;14 5S S160 S165. Open 10. Timothy R Sterling, Gibril Njie, Dominik Zenner et al. Guidelines for the Treatment of Latent Tuberculosis Infection: Recommendations from the National Tuberculosis Controllers Association and CDC, 2020. MMWR Recomm Rep. 2020 Feb 14;69 1 1 11. Open 11. Migliori GB, Sotgiu G, Rosales-Klintz S et al. ERS/ECDC Statement: European Union standards for tuberculosis care, 2017 update. Eur Respir J. 2018 May 17;51 5 . pii: 1702678. Open 12. No authors listed. WHO consolidated guidelines on tuberculosis: module 5 management of tuberculosis in children and adolescents. Geneva: World Health Organization; 2022. Open https://web.pathway.md/diseases/recEHAIr9AnzPn9ci 8/9 6/29/23, 11:37 PM Pulmonary tuberculosis Pathway 13. No authors listed. WHO consolidated guidelines on tuberculosis: module 2 screening: systematic screening for tuberculosis disease. Geneva: World Health Organization; 2021. Open https://web.pathway.md/diseases/recEHAIr9AnzPn9ci 9/9