Is moxifloxacin (a fluoroquinolone antibiotic) added to the standard treatment regimen for an adult patient with newly diagnosed drug-sensitive pulmonary tuberculosis?

Moxifloxacin in New Drug-Susceptible Tuberculosis Regimens

Yes, moxifloxacin is now added to a novel 4-month treatment regimen for newly diagnosed drug-susceptible pulmonary tuberculosis in patients aged ≥12 years, as an alternative to the standard 6-month regimen. 1

The New 4-Month Rifapentine-Moxifloxacin Regimen

The CDC recommends a 4-month daily regimen consisting of rifapentine (RPT), moxifloxacin (MOX), isoniazid (INH), and pyrazinamide (PZA) based on a large randomized controlled trial (Study 31/A5349) that demonstrated noninferiority to the standard 6-month regimen. 1 This regimen consists of:

• Intensive phase (8 weeks): Daily RPT, MOX, INH, and PZA 1
• Continuation phase (9 weeks): Daily RPT, INH, and MOX 1
• Total duration: 119 doses completed within 5 months 1

The trial enrolled 2,516 participants across 13 countries and showed that the rifapentine-moxifloxacin regimen had comparable efficacy (15.5% vs. 14.6% unfavorable outcomes) with no difference in serious adverse events compared to standard therapy. 2

Who Qualifies for This Regimen

Eligible patients include: 3

• Adults and adolescents aged ≥12 years with body weight ≥40 kg 3
• Drug-susceptible pulmonary tuberculosis (confirmed susceptibility to isoniazid, rifamycins, fluoroquinolones, and pyrazinamide) 3
• HIV-positive patients with CD4 counts ≥100 cells/μL on efavirenz-based antiretroviral therapy 3
• Patients with cavitary disease on chest radiograph (treatment duration is independent of cavitation status) 3
• Culture-negative but clinically suspected paucibacillary pulmonary TB 1, 3

Absolute Exclusions for the 4-Month Moxifloxacin Regimen

Do not use this regimen in: 3

• Patients aged <12 years or body weight <40 kg 3
• Known or suspected drug-resistant TB (resistance to isoniazid, rifamycins, fluoroquinolones, or pyrazinamide) 3
• Patients who received >5 doses of isoniazid, rifampin, rifabutin, rifapentine, pyrazinamide, or any fluoroquinolone in the preceding 30 days 3
• Prior TB treatment with >14 consecutive days of multidrug TB treatment in the preceding 6 months 3
• HIV-positive patients with CD4 counts <100 cells/μL 3
• HIV-positive patients on antiretroviral therapy other than efavirenz-based regimens (unless no drug-drug interactions exist) 3

Situations Requiring Clinical Consultation Before Starting

Consult TB experts for: 3

• ALT or AST >3 times the upper limit of normal 3
• Total bilirubin >2.5 times the upper limit of normal 3
• Preexisting advanced liver disease 3
• Serum creatinine >2 times the upper limit of normal 3
• Renal insufficiency or end-stage renal disease 3
• Plasma potassium level <3.5 mEq/L 3

Critical Monitoring Requirements

Baseline testing must include: 1

• Rapid molecular drug-susceptibility testing for isoniazid, pyrazinamide, rifampin, and fluoroquinolones 1
• Sputum for acid-fast bacilli smear and culture 1
• Chest radiograph 1
• Liver function tests (ALT, AST, bilirubin, alkaline phosphatase) 1
• Platelet count, creatinine, potassium, calcium, and magnesium 1
• HIV testing with CD4 count and viral load if positive 1

Monthly monitoring includes: 1

• Sputum for AFB smear and culture until two consecutive specimens are negative 1
• Weight assessment 1
• Symptom review and adverse event monitoring 1

Important Clinical Pitfalls

Common mistake: Using moxifloxacin-containing 4-month regimens that replace ethambutol OR isoniazid in standard regimens without rifapentine. These regimens have been shown to increase relapse rates substantially (RR 3.56,95% CI 2.37-5.37) and should not be used. 4 The key distinction is that the CDC-recommended regimen uses high-dose rifapentine (not rifampin) combined with moxifloxacin. 1

Thrice-weekly dosing: Do not use thrice-weekly moxifloxacin regimens, as these have demonstrated inferior outcomes with TB recurrence rates of 15% compared to 6% with standard therapy. 5 The CDC-recommended regimen requires daily dosing. 1

Treatment completion criteria: The regimen is considered complete based on total doses taken (119 doses), not calendar time. Intensive phase doses (56) must be completed within 70 days, and continuation phase doses (63) within 84 days of intensive phase completion. 1

Alternative Context: Drug-Resistant TB

For multidrug-resistant or rifampin-resistant TB, moxifloxacin or levofloxacin should be included in longer regimens (18-20 months) as Group A core agents with strong recommendation. 1 However, this is a completely different clinical scenario from newly diagnosed drug-susceptible TB. 1