Official American Thoracic Society/Centers for Disease ...

1 Clinical Infectious DiseasesIDSA GUIDELINEO fficial American Thoracic Society/Centers for DiseaseControl and Prevention/Infectious Diseases Society ofAmerica Clinical Practice Guidelines: Treatment ofDrug-Susceptible TuberculosisPayam Nahid,1 Susan E. Dorman,2 Narges Alipanah,1 Pennan M. Barry,3 Jan L. Brozek,4 Adithya Cattamanchi,1 Lelia H. Chaisson,1 Richard E. Chaisson,2 Charles L. Daley,5 Malgosia Grzemska,6 Julie M. Higashi,7 Christine S. Ho,8 Philip C. Hopewell,1 Salmaan A. Keshavjee,9 Christian Lienhardt,6 Richard Menzies,10 Cynthia Merrifield,1 Masahiro Narita,12 Rick O Brien,13 Charles A. Peloquin,14 Ann Raftery,1 Jussi Saukkonen,15H. Simon Schaaf,16 Giovanni Sotgiu,17 Jeffrey R. Starke,18 Giovanni Battista Migliori,11and Andrew Vernon81 University of California, San Francisco;2 Johns Hopkins University, Baltimore, Maryland;3 California Department of Public Health, Richmond;4 McMaster University, Hamilton, Ontario, Canada;5 National Jewish Health, Denver, Colorado;6 World Health Organization, Geneva, Switzerland;7 tuberculosis Control Section, San Francisco Department of Public Health, California;8 Division ofTuberculosis Elimination, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia;9 Harvard Medical School, Boston,Massachusetts;10 McGill University, Montreal, Quebec, Canada;11 WHO Collaborating Centre for TB and Lung Diseases, Fondazione S.

2 Maugeri Care and Research Institute, Tradate, Italy;12 tuberculosis Control Program, Seattle and King County Public Health, and University of Washington, Seattle;13 Ethics Advisory Group, International Union Against TB and Lung Disease , Paris, France;14 University of Florida, Gainesville;15 Boston University, Massachusetts;16 Department of Paediatrics and Child Health, Stellenbosch University, Cape Town, South Africa;17 University of Sassari, Italy;and18 Baylor College of Medicine, Houston, TexasThe American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America jointlysponsored the development of this guideline for the treatment of drug-susceptible tuberculosis , which is also endorsed by the Eu-ropean Respiratory Society and the US National tuberculosis Controllers Association. Representatives from the American Academyof Pediatrics, the Canadian Thoracic Society, the International Union Against tuberculosis and Lung Disease , and the World HealthOrganization also participated in the development of the guideline.

3 This guideline provides recommendations on the clinical andpublic health management of tuberculosis in children and adults in settings in which mycobacterial cultures, molecular and phe-notypic drug susceptibility tests, and radiographic studies, among other diagnostic tools, are available on a routine basis. For allrecommendations, literature reviews were performed, followed by discussion by an expert committee according to the Grading ofRecommendations, Assessment, Development and Evaluation methodology. Given the public health implications of prompt diag-nosis and effective management of tuberculosis , empiric multidrug treatment is initiated in almost all situations in which activetuberculosis is suspected. Additional characteristics such as presence of comorbidities, severity of Disease , and response to treatmentinfluence management decisions. Specific recommendations on the use of case management strategies (including directly observedtherapy), regimen and dosing selection in adults and children (daily vs intermittent), treatment of tuberculosis in the presence ofHIV infection (duration of tuberculosis treatment and timing of initiation of antiretroviral therapy), as well as treatment of extrap-ulmonary Disease (central nervous system, pericardial among other sites) are provided.

4 The development of more potent and better-tolerated drug regimens, optimization of drug exposure for the component drugs, optimal management of tuberculosis in specialpopulations, identification of accurate biomarkers of treatment effect, and the assessment of new strategies for implementing regi-mens in thefield remain key priority areas for research. See the full-text online version of the document for detailed discussion of themanagement of tuberculosis and recommendations for tuberculosis ; HIV infections; antitubercular agents; case management; public SUMMARYThe American Thoracic Society (ATS), Centers for Disease Con-trol and Prevention (CDC), and Infectious Diseases Society ofAmerica (IDSA) jointly sponsored the development of thisguideline on the treatment of drug-susceptible tuberculosis ,which is also endorsed by the European Respiratory Society(ERS) and the US National tuberculosis Controllers Association(NTCA). This guideline provides recommendations on the clin-ical and public health management of tuberculosis in childrenand adults in settings in which mycobacterial cultures, molecularReceived 4 June 2016; accepted 6 June guidelines were endorsed by the European Respiratory Society (ERS) and the US Na-tional tuberculosis Controllers Association (NTCA).

5 It is important to realize that guidelines can-not always account for individual variation among patients. They are not intended to supplantphysician judgment with respect to particular patients or special clinical situations. The spon-soring and endorsing societies consider adherence to these guidelines to be voluntary, with theultimate determination regarding their application to be made by the physician in the light ofeach patient s individual : P. Nahid, University of California, San Francisco, San Francisco General Hos-pital, Pulmonary and Critical Care Medicine, 1001 Potrero Ave, 5K1, San Francisco, CA Infectious Diseases The Author 2016. Published by Oxford University Press for the Infectious Diseases Societyof America. All rights reserved. For permissions, e-mail Clinical Practice Guidelines for Drug-Susceptible TB CID 1 Clinical Infectious Diseases Advance Access published August 10, 2016 at IDSA member on August 11, 2016 from and phenotypic drug susceptibility tests, and radiographic stud-ies, among other diagnostic tools, are available on a routine PICO (population, intervention, comparators, outcomes)questions and associated recommendations, developed basedon the evidence that was appraised using GRADE (Grading ofRecommendations Assessment, Development, and Evaluation)methodology [1, 2], are summarized below.

6 A carefully selectedpanel of experts, screened for conflicts of interest, including spe-cialists in pulmonary medicine, infectious diseases, pharmacoki-netics, pediatrics, primary care, public health, and systematicreview methodology were assembled and used GRADE methodsto assess the certainty in the evidence (also known as the qualityof evidence) and strength of the recommendations (seeSupple-mentary Appendix A: Methodsand Table1). This executivesummary is a condensed version of the panel s recommenda-tions. Additional detailed discussion of the management of pul-monary and extrapulmonary tuberculosis is available in the full-text version of this OF ANTITUBERCULOSIS THERAPYT reatment of tuberculosis is focused on both curing the individ-ual patient and minimizing the transmission ofMycobacteriumtuberculosisto other persons, thus, successful treatment of tu-berculosis has benefits both for the individual patient and thecommunity in which the patient objectives of tuberculosis therapy are (1) to rapidly re-duce the number of actively growing bacilli in the patient, there-by decreasing severity of the Disease , preventing death andhalting transmission ofM.

7 tuberculosis ; (2) to eradicate popula-tions of persisting bacilli in order to achieve durable cure (pre-vent relapse) after completion of therapy; and (3) to preventacquisition of drug resistance during decision to initiate combination chemotherapy for tu-berculosis is based on clinical, radiographic, laboratory, patient,and public health factors (Figure1). In addition, clinical judg-ment and the index of suspicion for tuberculosis are critical inmaking a decision to initiate treatment. For example, in patients(children and adults) who, based on these considerations, havea high likelihood of having tuberculosis or are seriously ill witha disorder suspicious for tuberculosis , empiric treatment with a4-drug regimen (Tables2 and 3) should be initiated promptlyeven before the results of acid-fast bacilli (AFB) smear micros-copy, molecular tests, and mycobacterial culture are years of investigation, including many clinical tri-als, have consistently supportedthe necessity of treating withmultiple drugs to achieve these treatment objectives, minimizedrug toxicity, and maximize the likelihood of treatment com-pletion [3, 4].

8 The success of drug treatment, however, dependsupon many factors, and numerous studies have found an in-creased risk of relapse among patients with signs of more exten-sive Disease (ie, cavitation or more extensive Disease on chestradiograph) [5 9], and/or slower response to treatment (ie, de-layed culture conversion at 2 3 months) [4, 6, 10, 11].ORGANIZATION AND SUPERVISION OF TREATMENTB ecause of the public health implications of prompt diagnosis andeffective treatment of tuberculosis , most low-incidence countriesdesignate a government public health agency as legal authority forcontrolling tuberculosis [12, 13]. The optimal organization of tu-berculosis treatment often requires the coordination of public andprivate sectors [14 16]. In most settings, a patient is assigned apublic health case manager who assesses needs and barriers thatmay interfere with treatment adherence [17]. With active inputfrom the patient and healthcare providers, the case manager, to-gether with the patient, develops an individualized case manage-ment plan with interventions to address the identified needs andbarriers [18 20] (see PICO Question 1 andSupplementary Ap-pendix B, Evidence Profiles 1 3).

9 The least restrictive publichealth interventions that are effective are used to achieve adher-ence, thereby balancing the rights of the patient and public that tuberculosis treatment requires multiple drugs be givenfor several months, it is crucial that the patient be involved in ameaningful way in making decisions concerning treatment super-vision and overall care. International standards have been devel-oped that also emphasize the importance of using patient-centered approaches to the management of tuberculosis [14 16].Key considerations when developing a case management planinclude (1) improving treatment literacy by educating theTable 1. Interpretation of Strong and Conditional Grading of Recommendations Assessment, Development, and Evaluation-Based RecommendationsImplicationsfor:Strong RecommendationConditional RecommendationPatientsMost individuals in this situation would want the recommended courseof action, and only a small proportion would majority of individuals in this situation would want the suggestedcourse of action, but many would individuals should receive the intervention.

10 Adherence to thisrecommendation according to the guideline could be used as aquality criterion or performance indicator. Formal decision aids arenot likely to be needed to help individuals make decisions consistentwith their values and that different choices will be appropriate for individualpatients and that you must help each patient arrive at a managementdecision consistent with his or her values and preferences. Decisionaids may be useful in helping individuals to make decisionsconsistent with their values and recommendation can be adopted as policy in most will require substantial debate and involvement of : Grading of Recommendations Assessment, Development and Evaluation Working Group [1, 2].2 CID Nahid et al at IDSA member on August 11, 2016 from patient about tuberculosis and its treatment, including possibleadverse effects [21,22];(2) discussing expected outcomes of treat-ment, specifically the ability to cure the patient of the Disease ; (3)reviewing methods of adherence support and plans for assessingresponse to therapy; and (4) discussing infectiousness and infec-tion control measures using terminology that is appropriate tothe culture, language, age, and reading level of the patient [23].