What are the 2025 CDC guidelines for treating tuberculosis (TB) with ethambutol and moxifloxacin?

2025 CDC Guidelines for TB Treatment Using Ethambutol and Moxifloxacin

For drug-resistant tuberculosis treatment, the 2025 CDC guidelines recommend including ethambutol only when other more effective drugs cannot be assembled to achieve a total of five drugs in the regimen, while moxifloxacin (or levofloxacin) is strongly recommended as a core component of all drug-resistant TB regimens. 1

Core Principles of Drug-Resistant TB Treatment

Drug Selection Algorithm

1. First-line drugs (Group A - must include):

   • Moxifloxacin or levofloxacin (later-generation fluoroquinolones)
   • Bedaquiline
   • Linezolid 1, 2

2. Second-line drugs (Group B - add at least one):

   • Clofazimine
   • Cycloserine/terizidone 1, 2

3. Third-line drugs (Group C - add only if needed):

   • Ethambutol (only if more effective drugs cannot be assembled)
   • Pyrazinamide (if susceptibility confirmed)
   • Delamanid
   • Carbapenems with amoxicillin-clavulanate
   • Amikacin or streptomycin (if susceptibility confirmed) 1, 2

Treatment Duration

• Intensive phase: 5-7 months after culture conversion
• Continuation phase: until total treatment reaches 15-21 months after culture conversion
• For pre-XDR and XDR-TB: 15-24 months after culture conversion 1

Specific Roles of Ethambutol and Moxifloxacin

Ethambutol

• Role: Relegated to Group C (third-line) drugs in drug-resistant TB treatment
• Indication: Should only be included when other more effective drugs cannot be assembled to achieve a total of five drugs in the regimen 1, 2
• Dosing: Standard weight-based dosing (15-20 mg/kg daily)
• Monitoring: Regular visual acuity and color discrimination testing required due to risk of optic neuritis 1

Moxifloxacin

• Role: Group A (first-line) drug for drug-resistant TB treatment
• Indication: Strongly recommended for inclusion in all drug-resistant TB regimens 1, 2
• Preference: Levofloxacin may be preferred over moxifloxacin in some cases due to fewer adverse events and less QTc prolongation 2
• Special use: For isoniazid-resistant TB, adding moxifloxacin to a 6-month regimen of daily rifampin, ethambutol, and pyrazinamide is recommended 2

Special Treatment Scenarios

Isoniazid-Resistant TB

1. Recommended regimen: Add a later-generation fluoroquinolone (moxifloxacin or levofloxacin) to a 6-month regimen of daily rifampin, ethambutol, and pyrazinamide 2
2. Pyrazinamide duration: Can be shortened to 2 months in selected situations:
   • Non-cavitary disease
   • Lower burden disease
   • Toxicity from pyrazinamide 2

Shorter Regimens

For eligible patients (no extensive pulmonary disease, no severe extrapulmonary TB, no fluoroquinolone resistance), a 6-month all-oral bedaquiline-containing regimen may be considered with:

• 4-6 month intensive phase including moxifloxacin/levofloxacin, clofazimine, pyrazinamide, ethambutol, and other drugs
• 5-month continuation phase with moxifloxacin/levofloxacin, clofazimine, pyrazinamide, and ethambutol 2

Monitoring and Safety Considerations

Moxifloxacin Safety

• QTc prolongation risk, especially when combined with bedaquiline
• Regular ECG monitoring recommended
• Levofloxacin may be preferred over moxifloxacin for fewer adverse events and less QTc prolongation 2

Ethambutol Safety

• Regular monitoring for optic neuritis required
• Monthly visual acuity and color discrimination testing
• Dose adjustment required in renal impairment 1

Common Pitfalls to Avoid

1. Inadequate number of effective drugs: Always aim for at least 5 effective drugs in the intensive phase for drug-resistant TB 1

2. Adding a single drug to a failing regimen: Always add at least two drugs to which the organism is likely susceptible 1

3. Overlooking drug interactions: Monitor for QTc prolongation when combining moxifloxacin with bedaquiline 2

4. Inadequate drug susceptibility testing: Treatment should be guided by susceptibility results whenever possible 1

5. Poor adherence monitoring: Directly observed therapy is strongly recommended for all drug-resistant TB regimens 1

The 2025 CDC guidelines emphasize a more targeted approach to TB treatment, with moxifloxacin playing a central role while ethambutol is reserved for cases where more effective alternatives are not available.