American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: Treatment of Tuberculosis

American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: Treatment of Tuberculosis Official Joint Statement of the ATS, CDC, and IDSA; Am J Respir Crit Care Med 2003;167:603 The updated official recommendation for the management of tuberculosis is summarized in the table below: Treatment of Drug Susceptible TB ( Tables 1 and 3) Priorities for DOT (Table 2)Table 1: Treatment Drug-Susceptible TBTable 2: Directly Observed TherapyTable 3: Doses of Antituberculosis Drugs Pulmonary TB with positive smear Treatment failure Drug resistance Relapse HIV infection Prior treatment Current or prior drug abuse Psychiatric illness Memory impairment Prior nonadherence Components of patient-centered treatment Transportation vouchers Child care Convenient hours and locations Address language barriers Reminder systems and follow-up of missed appointments Social service assistance Outreach workers Integration of TB care with other care Incentives: food stamps, meals, restaurant coupons, housing assistance, clothing etc., books, stipends, patient contract (Chest 1997;111:1168; Am J Public Health 1998;88:1052; Lancet 2000;355:1345) Treatment Interruptions Initial phase Duration of interruption <14 days: Continue therapy; if not completed in 3 months, restart Duration 14 days: restart Continuation phase 80% doses: no additional therapy <80% doses: Duration of interruption <3 months: Continue; if not completed in 6 months, restart Duration of interruption 3 months: Restart 4 drug initial phase Dose: Second-Line Drugs Rifabutin: 300 mg (half the standard rifampin dose) Cycloserine: 10-15 mg/kg/d, usually 500-750 mg bid Ethionamide: 15-20 mg/kg/d, usually 500-750 mg qd Streptomycin: 15 mg/kg/d, usually 1 g qd. Age >50 years: 10 mg/kg/d, usually 750 mg qd. Streptomycin is given intramuscularly or intravenously 5-7 days/wk × 2-4 months then twice to thrice a week after culture conversion. Amikacin/kanamycin/capreomycin: same as streptomycin PAS: 8-12 g/d in 2-3 doses Levofloxacin: 500-1000 mg/d Gatifloxacin/moxifloxacin: 400 mg/d Duration of Therapy With Drug-Sensitive Strains Initial 8-week course: identical for all patients Continuation phase: Cavitation or positive culture at 2 months TABLETableNo cavitation, negative culture at 2 months, negative HIV, and no extrapulmonary TB: RIF/INH or RPT/INH × 4 months HIV or extrapulmonary TB: INH/RIF (only) Rationale: risk for relapse with cavitation and/or positive sputum at 2 months using standard initial 4 drug initial phase and INH/RIF twice a week × 16 weeks USPH study 22 (Lancet 2002;360:528). TABLETable Drug Information: Formulations, Adverse Reactions, and Recommendations for Monitoring for First-Line Drugs INH Formulation: 50-, 100-, and 300-mg tablets, also syrup and IV formulations Liver: ALT in 10-20%, clinical hepatitis in 0.6%, INH/RIF in 2.7%. Risk with EtOH, prior liver disease, and postpartum fatal hepatitis in 0.02%. Peripheral neuropathy: dose related, frequency 0.2%, risk with other causes peripheral neuropathy (diabetes, HIV, drugs, EtOH, pregnancy). Prevented with pyridoxine 25 mg/d. Rare: CNS toxicity, LE syndrome, hypersensitivity reactions, monoamine poisoning, flushing with exposure to wine, cheese, etc. Pregnancy: safe Drug interaction: levels of phenytoin and carbamazepine (but by RIF) Monitoring: usually none. Monitor LFTs monthly if preexisting liver disease or with development of abnormal LFTs that does not require D/C therapy. RIF Forms: 150-mg capsules Cutaneous reactions: pruritis ± rash in 6%, drug usually continued Flu syndrome: 0.4%-0.7% taking RIF twice a week Liver: cholestatic hepatitis; hepatotoxicity in 2.7% given INH/RIF Orange discoloration body fluids: Warn patients, clothing and contact lens may be stained Pregnancy: safe Interactions: Extensive, reduce the following to ineffective levels: oral contraceptives, methadone, warfarin, protease inhibitors (see http://www.cdc.gove/nchstp/tb/) Monitoring: none PZA Formulation: 500-mg tablets Liver: dose-related hepatotoxicity; 1% at 25 mg/kg Nongouty polyarthralgias: Up to 40%, rarely serious enough to D/C; Rx with ASA, NSAIDs Hyperuracemia: expected and not consequential; acute gout is rare. GI intolerance: usually mild Pregnancy: little information; use when benefit justifies an unquantified risk. Monitoring: uric acid levels are unnecessary but may be surrogate for compliance. LFTs when baseline liver disease and when given with RIF for latent TB. EMB Formulations: 100- and 400-mg tablets Ocular: decreased acuity or decreased red-green discrimination. Risk is dose related and minimal at 15 mg/kg; risk increases with daily administration and renal failure. Pregnancy: safe Monitoring: baseline visual acuity and Ishihara test of color discrimination. Inquire about vision changes at each monthly visit and warn to contact clinic immediately if change in vision. Monthly test of acuity and color discrimination with doses <15-20 mg/kg, duration >2 months or renal failure. Modifications of Standard Regimen in Special Populations HIV Infection: Recommendations are identical for general population except: CD4 < 100/mm3: Continuation phase should be daily or thrice a week Once weekly, rifapentine regimen should not be used. Positive cultures at 2 months:Strongly consider 7-month continuation phase (total 9 months) In absence of prior HIV therapy and CD4 < 350/mm3: delay antiretroviral drugs for 4-8 weeks. RIF may be used with 2 NRTIs + EFV, RTV ISQV (Invirase or Fortovase) or AZT/3TC/ABC. Rifabutin combined with other PIs and NNRTI requires dose adjustment of both. See http://www.cdc.gov/nchstp/tb/www.medscape.com/updates/quickguide. When starting NNRTI or PI in patient receiving RIF, substitute rifabutin 2 weeks prior to NNRTI or PI to give a 2-week washout period for RIF Paradoxical reaction: frequency in 7%-36%; clinical features: high fever, increased adenopathy, CNS lesions, pulmonary infiltrates, and pleural effusions. Treatment is symptomatic; if severe, give prednisone 1 mg/kg and reduce dose at 1-2 weeks. Extrapulmonary TB Standard 4 drug initial phase followed by INH/RIF for 4-7 months except for CNS TB, which is treated 9-12 months. TABLETableCulture negative suspected active TB Low probability: No initial treatment Culture negative at 2 months and x-ray unchanged RIF ± INH × 4 months INH × 9 months RIF/PZA × 2 months High probability INH/RIF/EMB/PZA × 2 months Culture negative at 2 months and x-ray improved: INH/RIF × 2 months Culture negative and x-ray unchanged: D/C therapy Pregnancy and breast feeding Regimen: INH/RIF/EMB × 9 months or standard treatment with INH/RIF/EMB/PZA × 2 months then INH/RIF × 4 months. The issue is safety of PZA, which has no evidence of adverse effects in pregnancy but inadequate experience to assure safety. Streptomycin: Only anti-TB drug with documented harm to human fetuses. TABLETableTableHepatic Disease Regimen excluding INH: RIF/PZA/EMB × 6 months Regimen excluding PZA: INH/RIF/EMB × 2 months then INH/RIF × 7 months Regimen for severe liver disease: RIF/fluoroquinolone/cycloserine/aminoglycoside × 18 months or Streptomycin/EMB, fluoroquinolone/another second-line drug × 18-24 months Comment: This guideline represents marching orders for the management of tuberculosis in the US. Highlights compared with the older version are the following: There is emphasis on sputum cultures at the end of the initial (8-week) phase of treatment to determine the risk of relapse. The major new drugs included are rifabutin, rifapentine, and fluoroquinolones. The adequacy of treatment is defined by the number of doses over a specified duration. Guidelines are provided for special populations including HIV infection, extrapulmonary TB, culture-negative TB, pregnancy, hepatic failure, and renal disease. Management of drug-resistant strains is updated. There is continued emphasis on DOT and good evidence to support enhanced DOT including use of incentives. The standard regimen for pulmonary TB with drug-sensitive strains is 6 months, except for patients with both cavitation at baseline and positive cultures at 8 weeks who should be treated 9 months. Monitoring of patients receiving first-line agents without comorbidities is limited to a baseline visual acuity and test of color discrimination for EMB toxicity. Liver function tests are not suggested as routine, unless there is baseline liver disease or elevated tests during therapy that do not require discontinuation. No mention is made of limiting alcohol ingestion. Corticosteroids are recommended for tuberculosis pericarditis, CNS TB, and severe paradoxical reactions. TABLETable