Treatment of Multidrug-Resistant Tuberculosis (MDR-TB)
The optimal treatment for MDR-TB requires a regimen of at least five effective drugs in the intensive phase, with bedaquiline and a later-generation fluoroquinolone (levofloxacin or moxifloxacin) as core components, followed by at least four drugs in the continuation phase, with a total treatment duration of 15-21 months after culture conversion. 1, 2
Core Components of MDR-TB Treatment
- A regimen should include at least five effective drugs during the intensive phase and four drugs during the continuation phase to which the patient's M. tuberculosis isolate has documented or high likelihood of susceptibility 3, 1
- The following drugs should form the backbone of MDR-TB treatment:
- Bedaquiline (strongly recommended as a core component) 1, 2
- Later-generation fluoroquinolone (levofloxacin or moxifloxacin) if susceptibility is confirmed 1, 2
- Linezolid (conditionally recommended as an effective component) 1, 2
- Clofazimine (conditionally recommended as an effective component) 1, 2
- Cycloserine or terizidone (conditionally recommended) 1, 2
Treatment Duration
- The intensive phase should last 5-7 months after culture conversion 1, 2
- The total treatment duration should be 15-21 months after culture conversion 1, 2
- For pre-XDR and XDR-TB, treatment should be extended to 15-24 months after culture conversion 1, 2
Drugs NOT Recommended for MDR-TB Treatment
- Kanamycin or capreomycin (injectable agents) should not be used 3, 2
- Macrolides (azithromycin and clarithromycin) should not be included 3, 2
- Amoxicillin-clavulanate alone should not be used (only use with carbapenems) 3, 2
- Ethionamide/prothionamide should not be used if more effective drugs are available 3, 2
- p-aminosalicylic acid should not be used if more effective drugs are available 3, 2
Additional Treatment Options
- Delamanid may be included in the treatment of patients with MDR/RR-TB aged >3 years on longer regimens 3
- Injectable agents (amikacin or streptomycin) may be included when susceptibility is confirmed 3, 2
- Carbapenems (always to be used with amoxicillin-clavulanic acid) may be included when needed 3, 2
- Pyrazinamide may be included if susceptibility is confirmed 2
Special Considerations
- Consultation should be requested with a TB expert when there is suspicion of or confirmation of drug-resistant TB 3
- Molecular drug susceptibility tests (DSTs) should be obtained for rapid detection of resistance mutations 3
- A 9-12 month shorter regimen may be considered for select patients who meet specific criteria, though the guideline committee cannot make a definitive recommendation for or against this standardized shorter-course regimen 3, 2
- Surgical resection may improve outcomes in selected cases, particularly for XDR-TB 4
- Using at least four effective drugs and maintaining a body mass index ≥18.5 are independent predictors of favorable outcomes 4
Common Pitfalls to Avoid
- Using fewer than five effective drugs in the intensive phase leads to poorer outcomes 1, 2
- Insufficient treatment duration (less than 15 months after culture conversion) is associated with higher relapse rates 1, 2
- Poor adherence to therapy is strongly associated with treatment failure 5
- Using older fluoroquinolones, especially ciprofloxacin, results in higher relapse rates and longer time to sputum-culture conversion 6
- Resistance to fluoroquinolones significantly reduces the likelihood of treatment success 5
Monitoring Treatment Response
- Monthly sputum culture for acid-fast bacilli in the initial months of treatment helps predict clinical outcomes 5
- Negative sputum cultures after 2-3 months of therapy are highly predictive of cure 5
- Therapeutic drug monitoring should be considered in patients who adhere to therapy but fail to respond appropriately, especially those with HIV co-infection who may have malabsorption syndrome 7