Does the new guideline suggest moxifloxacin (Moxifloxacin) as an alternative to ethambutol (Ethambutol) in treating pulmonary tuberculosis?

Moxifloxacin as an Alternative to Ethambutol in Tuberculosis Treatment

The 2019 ATS/CDC/ERS/IDSA guidelines suggest using moxifloxacin instead of ethambutol only in specific situations, particularly for isoniazid-resistant TB, but do not recommend wholesale replacement of ethambutol with moxifloxacin in standard TB treatment regimens. 1

Current Guideline Recommendations

Role of Ethambutol

• Ethambutol remains part of standard first-line treatment regimens for drug-susceptible TB 2
• Guidelines suggest including ethambutol in MDR-TB regimens only when more effective drugs cannot be assembled to achieve a total of five effective drugs in the regimen (conditional recommendation) 1
• Ethambutol's primary value lies in preventing emergence of resistance, which is a substantial concern among patients with MDR-TB 1

Role of Fluoroquinolones (Moxifloxacin)

• The 2019 guidelines strongly recommend including a later-generation fluoroquinolone (levofloxacin or moxifloxacin) in MDR-TB treatment regimens 1
• For isoniazid-resistant TB specifically, guidelines suggest adding a later-generation fluoroquinolone to a 6-month regimen of daily rifampin, ethambutol, and pyrazinamide (conditional recommendation) 1
• In the WHO MDR-TB drug classification, fluoroquinolones (levofloxacin/moxifloxacin) are in Group A (highest priority drugs), while ethambutol is in Group C (lower priority) 1

Specific Scenarios Where Moxifloxacin May Replace Ethambutol

Isoniazid-Resistant TB

• For patients with isoniazid-resistant TB, guidelines specifically suggest adding a later-generation fluoroquinolone to rifampin, ethambutol, and pyrazinamide for 6 months 1
• In this scenario, moxifloxacin is added to, not substituted for, ethambutol 1

Ocular Complications

• Moxifloxacin can be considered as an alternative to ethambutol in patients at high risk for or experiencing ethambutol-related ocular toxicity 3
• Ethambutol is associated with optic neuropathy (including optic neuritis and retrobulbar neuritis) that manifests as decreased visual acuity, scotomata, color blindness, or visual defects 1

MDR-TB Treatment

• In the shorter all-oral bedaquiline-containing regimen for MDR/RR-TB, both moxifloxacin and ethambutol are included, not as alternatives but as complementary drugs 1
• Levofloxacin is generally preferred over moxifloxacin for fewer adverse events and less QTc prolongation 1

Evidence on Moxifloxacin vs. Ethambutol

Efficacy

• A phase II trial showed that moxifloxacin substitution for ethambutol resulted in higher culture conversion rates at 8 weeks (80% vs. 63%, p=0.03) 4
• However, shortened 4-month regimens containing moxifloxacin that replaced ethambutol or isoniazid increased relapse rates substantially compared to standard 6-month regimens 2, 5

Safety Considerations

• Moxifloxacin is generally well-tolerated, with nausea being the most significant adverse effect reported 6
• Ethambutol is associated with serious adverse events in approximately 0.5% of patients, primarily ocular toxicity 1
• When ethambutol is used, patients should be monitored monthly for signs of ocular toxicity 1

Clinical Decision-Making Algorithm

1. For drug-susceptible pulmonary TB:

   • Use standard regimen with ethambutol (with isoniazid, rifampin, pyrazinamide) 2
   • Consider moxifloxacin substitution only if patient develops or is at high risk for ethambutol-related ocular toxicity 3

2. For isoniazid-resistant TB:

   • Add a later-generation fluoroquinolone (moxifloxacin or levofloxacin) to rifampin, ethambutol, and pyrazinamide 1
   • Maintain daily treatment rather than intermittent dosing 1

3. For MDR/RR-TB:

   • Follow WHO classification - prioritize Group A drugs (including moxifloxacin/levofloxacin) over Group C drugs (including ethambutol) 1
   • Include ethambutol only when more effective drugs cannot be assembled to achieve a total of five effective drugs 1

Important Caveats

• Drug susceptibility testing should guide therapy whenever possible 1
• The cross-resistance between fluoroquinolones is not complete - 81% of M. tuberculosis isolates resistant to ofloxacin were also resistant to moxifloxacin in European data 1
• When ethambutol is used, some experts recommend higher dosing (25 mg/kg) for increased efficacy, though this carries slightly greater risk of ocular toxicity 1
• All patients receiving ethambutol should be monitored for visual impairment; if detected, ethambutol should be discontinued 1