Treatment of Tuberculosis - Centers for Disease Control ...

1 Morbidity and Mortality Weekly ReportRecommendations and ReportsJune 20, 2003 / Vol. 52 / No. RR-11 INSIDE: Continuing Education Examinationdepartment of health and human servicesCenters for Disease Control and PreventionTreatment of TuberculosisAmerican Thoracic Society, CDC, and InfectiousDiseases Society of AmericaMMWRSUGGESTED CITATIONC enters for Disease Control and of Tuberculosis , American ThoracicSociety, CDC, and Infectious Diseases Society ofAmerica. MMWR 2003;52(No. RR-11):[inclusivepage numbers].The MMWR series of publications is published by theEpidemiology Program Office, Centers for DiseaseControl and prevention (CDC), Department ofHealth and Human Services, Atlanta, GA for Disease Control and PreventionJulie L. Gerberding, , W.

2 Fleming, Director for Public Health ScienceDixie E. Snider, Jr., , Director for ScienceEpidemiology Program OfficeStephen B. Thacker, , of Scientific and Health CommunicationsJohn W. Ward, , MMWR SeriesSuzanne M. Hewitt, Editor, MMWR SeriesC. Kay Smith-Akin, Technical Writer/EditorLynne McIntyre, EditorBeverly J. HollandLead Visual Information SpecialistMalbea A. HeilmanVisual Information SpecialistQuang M. DoanErica R. ShaverInformation Technology SpecialistsThe following drugs, which are suggested for use in selected cases,are not approved by the Food and Drug Administration for treatmentof Tuberculosis : rifabutin, amikacin, kanamycin, moxifloxacin,gatifloxacin, and Iseman, , has indicated that he has a financialrelationship with Ortho-McNeil, which manufactures Levaquin.

3 The remaining preparers have signed a conflict of interest disclosureform that verifies no conflict of 1 What s New In This Document .. 11. Introduction and Background .. 132. Organization and Supervision of Treatment .. 153. Drugs in Current Use .. 194. Principles of Antituberculosis Chemotherapy .. 325. Recommended Treatment Regimens .. 366. Practical Aspects of Treatment .. 427. Drug Interactions .. 458. Treatment in Special Situations .. 509. Management of Relapse, Treatment Failure,and Drug Resistance .. 6610. Treatment Of Tuberculosis in Low-Income Countries:Recommendations and Guidelines of the WHOand the IUATLD .. 7211. Research Agenda for Tuberculosis Treatment .. 74 Vol. 52 / RR-11 Recommendations and Reports1 This Official Joint Statement of the American Thoracic Society, CDC,and the Infectious Diseases Society of America was approved by theATS Board of Directors, by CDC, and by the Council of the IDSA inOctober 2002.

4 This report appeared in the American Journal ofRespiratory and Critical Care Medicine (2003;167:603 62) and is beingreprinted as a courtesy to the American Thoracic Society, the InfectiousDiseases Society of America, and the MMWR of TuberculosisAmerican Thoracic Society, CDC, and Infectious Diseases Society of AmericaPurposeThe recommendations in this document are intended toguide the Treatment of Tuberculosis in settings where myco-bacterial cultures, drug susceptibility testing, radiographic fa-cilities, and second-line drugs are routinely available. In areaswhere these resources are not available, the recommendationsprovided by the World Health Organization, the InternationalUnion against Tuberculosis , or national Tuberculosis controlprograms should be s New In This Document The responsibility for successful Treatment is clearlyassigned to the public health program or private provider,not to the patient.

5 It is strongly recommended that the initial Treatment strat-egy utilize patient-centered case management with anadherence plan that emphasizes direct observation oftherapy. Recommended Treatment regimens are rated according tothe strength of the evidence supporting their use. Wherepossible, other interventions are also rated. Emphasis is placed on the importance of obtainingsputum cultures at the time of completion of the initialphase of Treatment in order to identify patients at increasedrisk of relapse. Extended Treatment is recommended for patients withdrug-susceptible pulmonary Tuberculosis who have cavi-tation noted on the initial chest film and who have posi-tive sputum cultures at the time 2 months of Treatment iscompleted. The roles of rifabutin, rifapentine, and the fluoroquino-lones are discussed and a regimen with rifapentine in aonce-a-week continuation phase for selected patients isdescribed.

6 Practical aspects of therapy, including drug administra-tion, use of fixed-dose combination preparations, moni-toring and management of adverse effects, and druginteractions are discussed. Treatment completion is defined by number of dosesingested, as well as the duration of Treatment administra-tion. Special Treatment situations, including human immuno-deficiency virus infection, Tuberculosis in children,extrapulmonary Tuberculosis , culture-negative tuberculo-sis, pregnancy and breastfeeding, hepatic Disease andrenal Disease are discussed in detail. The management of Tuberculosis caused by drug-resistantorganisms is updated. These recommendations are compared with those of theWHO and the IUATLD and the DOTS strategy isdescribed.

7 The current status of research to improve Treatment for Successful TreatmentThe overall goals for Treatment of Tuberculosis are 1) to curethe individual patient, and 2) to minimize the transmission ofMycobacterium Tuberculosis to other persons. Thus, successfultreatment of Tuberculosis has benefits both for the individualpatient and the community in which the patient resides. Forthis reason the prescribing physician, be he/she in the publicor private sector, is carrying out a public health function withresponsibility not only for prescribing an appropriate regimenbut also for successful completion of therapy. Prescribing phy-sician responsibility for Treatment completion is a fundamen-tal principle in Tuberculosis Control . However, given a clearunderstanding of roles and responsibilities, oversight of treat-ment may be shared between a public health program and aprivate and Supervision of TreatmentTreatment of patients with Tuberculosis is most successfulwithin a comprehensive framework that addresses both clini-cal and social issues of relevance to the patient.

8 It is essentialthat Treatment be tailored and supervision be based on eachpatient s clinical and social circumstances (patient-centeredcare). Patients may be managed in the private sector, by publichealth departments, or jointly, but in all cases the healthdepartment is ultimately responsible for ensuring that adequate,appropriate diagnostic and Treatment services are available, andfor monitoring the results of 20, 2003It is strongly recommended that patient-centered care bethe initial management strategy, regardless of the source ofsupervision. This strategy should always include an adherenceplan that emphasizes directly observed therapy (DOT), inwhich patients are observed to ingest each dose of antituber-culosis medications, to maximize the likelihood of comple-tion of therapy.

9 Programs utilizing DOT as the central elementin a comprehensive, patient-centered approach to case man-agement (enhanced DOT) have higher rates of treatmentcompletion than less intensive strategies. Each patient s man-agement plan should be individualized to incorporate mea-sures that facilitate adherence to the drug regimen. Suchmeasures may include, for example, social service support, treat-ment incentives and enablers, housing assistance, referral fortreatment of substance abuse, and coordination of tuberculo-sis services with those of other Treatment RegimensThe recommended Treatment regimens are, in large part,based on evidence from clinical trials and are rated on thebasis of a system developed by the United States Public HealthService (USPHS) and the Infectious Diseases Society ofAmerica (IDSA).

10 The rating system includes a letter (A, B, C,D, or E) that indicates the strength of the recommendationand a roman numeral (I, II, or III) that indicates the quality ofevidence supporting the recommendation (Table 1).There are four recommended regimens for treating patientswith Tuberculosis caused by drug-susceptible these regimens are broadly applicable, there are modi-fications that should be made under specified circumstances,described subsequently. Each regimen has an initial phase of 2months followed by a choice of several options for the con-tinuation phase of either 4 or 7 months. The recommendedregimens together with the number of doses specified by theregimen are described in Table 2. The initial phases aredenoted by a number (1, 2, 3, or 4) and the continuationphases that relate to the initial phase are denoted by the num-ber plus a letter designation (a, b, or c).