Version May 2024
| |
| Step 1: Choose one later-generation fluoroquinolone | Levofloxacin |
| Moxifloxacin | |
| Step 2: Choose both of these prioritized drugs | Bedaquiline |
| Linezolid | |
| Step 3: Choose both of these prioritized drugs | Clofazimine |
| Cycloserine/terizidone | |
| Step 4: If needed, use the following drugs¶ | Pyrazinamide |
| DelamanidΔ | |
| Ethambutol | |
| Ethionamide or prothionamide◊ | |
| Imipenem-cilastatin or meropenem§ plus Clavulanic acid (available only when combined with amoxicillin, as amoxicillin-clavulanic acid) | |
| p-Aminosalicylic acid¥ | |
| High-dose isoniazid‡ | |
| Step 5: If a regimen cannot be assembled with five effective oral drugs, and the isolate is susceptible, use one of these injectable agents* | Amikacin |
| Streptomycin | |
| These drugs are no longer recommended for inclusion in MDR-TB regimens: | Capreomycin and kanamycin |
| Amoxicillin-clavulanate (when used without a carbapenem) | |
| Azithromycin and clarithromycin | |
TB: tuberculosis; MDR: multidrug-resistant; DST: drug susceptibility testing; PS: propensity score; IPDMA: individual patient data meta-analyses; INH: isoniazid.
* Amikacin and streptomycin should be used only when the patient's isolate is susceptible to these drugs. Because of their toxicity, these drugs should be reserved for when more-effective or less-toxic therapies cannot be assembled to achieve a total of five effective drugs.
¶ Patient preferences in terms of the harms and benefits associated with injectables (the use of which is no longer obligatory), the capacity to appropriately monitor for significant adverse effects, consideration of drug–drug interactions, and patient comorbidities should be considered in selecting Step 4 agents over injectables. Ethambutol and pyrazinamide had mixed/marginal performance on outcomes assessed in our PS-matched IPDMA; however, some experts may prefer these drugs over injectable agents to build a regimen of at least five effective oral drugs. Use pyrazinamide and ethambutol only when the isolate is documented as susceptible.
Δ Data on dosing and safety of delamanid are available in children >3 years of age.
◊ Mutations in the inhA region of the Mycobacterium tuberculosis genome can confer resistance to ethionamide/prothionamide as well as to INH. In this situation, ethionamide/prothionamide may not be a good choice unless the isolate is shown to be susceptible with in vitro testing.
§ Divided daily intravenous dosing limits feasibility. Optimal duration of use not defined.
¥ Fair/poor tolerability and low performance. Adverse effects reported to be less common in children.
‡ Data not reviewed in our PS-matched IPDMA, but high-dose isoniazid can be considered despite low-level isoniazid resistance but not with high-level INH resistance.Adapted with permission of the American Thoracic Society. Copyright © 2019 American Thoracic Society. From: Nahid P, Mase SR, Migliori GB, et al. Treatment of drug-resistant tuberculosis: an official ATS/CDC/ERS/IDSA clinical practice guideline. Am J Respir Crit Care Med 2019; 200:e93. The American Journal of Respiratory and Critical Care Medicine is an official journal of the American Thoracic Society.
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