Drug-resistant tuberculosis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2]

Overview

Drug-resistant tuberculosis is caused by M. tuberculosis organisms that are resistant to at least one first-line anti-TB drug. Multidrug-resistant TB (MDR TB) is resistant to more than one anti-TB drug and at least isoniazid (INH) and rifampin (RIF). Treatment should be started with an empirical treatment of at least 4 drugs based on expert advice as soon as drug-resistant TB disease is suspected.

Multiple Drug-Resistant (MDR) Tuberculosis Adapted from WHO 2013 Treatment of tuberculosis: guidelines – 4th ed.

• MDR-TB is defined as resistance to isoniazid and rifampicin, with or without resistance to other first-line drugs.
• Medical treatment for MDR-TB consists of at least 4 drugs that have shown effectiveness against MDR. Within these 4 drugs must be included at least one drug from each group.
• Treatment duration will depend on the culture results. The duration of therapy should be > 18 months after culture is negative.
• Chronic cases with severe pulmonary disease may require more than 24 months of therapy.
• Drugs in each group must be used, in order of preference, as shown below.

MDR Tuberculosis   ▸  Adults   ▸  Children

MDR-TB Adults Standard Regimen Group 1: First-line oral drugs ▸ Pyrazinamide 20–30 mg/kg OR ▸ Ethambutol 15–25 mg/kg OR ▸ Rifabutin 5 mg/kg PLUS Group 2: Injectable drugs ▸ Capreomycin 15 mg/kg OR ▸ Kanamycin 15 mg/kg OR ▸ Amikacin 7.5-10 mg/kg OR ▸ Streptomycin 12–18 mg/kg PLUS Group 3: Fluoroquinolones ▸ Levofloxacin 500-1000 mg OR ▸ Moxifloxacin 400 mg OR ▸ Ofloxacin 400 mg PLUS Group 4:Oral bacteriostatic second-line drugs ▸ Ethionamide 15-20 mg/kg OR ▸ Protionamide OR ▸ Cycloserine 10-15 mg/kg OR ▸ Terizidone OR ▸ Para-aminosalicylic acid 8-12 g/d divided q8-12h Table adapted from WHO 2013 Treatment of tuberculosis: guidelines – 4th ed. MDR-TB Children Standard Regimen Group 1: First-line oral drugs ▸ Pyrazinamide OR ▸ Ethambutol OR ▸ Rifabutin PLUS Group 2: Injectable drugs ▸ Capreomycin OR ▸ Kanamycin OR ▸ Amikacin OR ▸ Streptomycin PLUS Group 3: Fluoroquinolones ▸ Levofloxacin OR ▸ Moxifloxacin OR ▸ Ofloxacin PLUS Group 4:Oral bacteriostatic second-line drugs ▸ Ethionamide OR ▸ Protionamide OR ▸ Cycloserine OR ▸ Terizidone OR ▸ Para-aminosalicylic acid Table adapted from WHO 2013 Treatment of tuberculosis: guidelines – 4th ed.

Further information: [[:Multi-drug-resistant tuberculosis]]

Extensively Drug-Resistant XDR Tuberculosis

• XDR-TB is defined as resistance to at least isoniazid and rifampicin, and to any fluoroquinolone, and to any of the three second-line injectables (amikacin, capreomycin, and kanamycin).
• Additional drugs are needed for XDR treatment regimen, these drugs are known to have some action against tuberculosis but are not routinely recommended for treatment of MDR-TB.
• These include clofazimine, linezolid, amoxicillin/clavulanate, thioacetazone, imipenem/cilastatin, clarithromycin and high-dose isoniazid.

XDR Tuberculosis   ▸  Adults   ▸  Children

XDR-TB Adults Standard Regimen Group 1: First-line oral drugs ▸ Pyrazinamide 20–30 mg/kg OR ▸ Ethambutol 15–25 mg/kg OR ▸ Rifabutin 5 mg/kg PLUS Group 4:Oral bacteriostatic second-line drugs ▸ Ethionamide 15-20 mg/kg OR ▸ Protionamide OR ▸ Cycloserine 10-15 mg/kg OR ▸ Terizidone OR ▸ Para-aminosalicylic acid 8-12 g/d divided q8-12h PLUS Group 5 (use at least 2 drugs) ▸ Clofazimine OR ▸ Amoxicillin/clavulanate OR ▸ Linezolid OR ▸ imipenem OR ▸ Clarithromycin OR ▸ Thioacetazone Table adapted from WHO 2013 Treatment of tuberculosis: guidelines – 4th ed. XDR-TB Children Preferred Regimen ▸