What are the fluoroquinolone (FQ)-based regimens for the treatment of multidrug-resistant tuberculosis (MDR-TB)?

Fluoroquinolone-Based Regimens for Drug-Resistant Tuberculosis

For multidrug-resistant tuberculosis (MDR-TB), fluoroquinolones—specifically later-generation agents like levofloxacin or moxifloxacin—are essential core components of treatment regimens and should be included in virtually all MDR-TB treatment plans unless documented resistance exists. 1

Core Role of Fluoroquinolones in MDR-TB Treatment

Standard MDR-TB Regimens

Fluoroquinolones form the backbone of MDR-TB therapy and are classified as Group A priority drugs alongside bedaquiline and linezolid. 1

• Later-generation fluoroquinolones (levofloxacin or moxifloxacin) are strongly preferred over older agents like ciprofloxacin or ofloxacin due to superior bactericidal activity and lower relapse rates 2, 3
• Levofloxacin is generally preferred over moxifloxacin because it causes fewer adverse events and less QTc prolongation 1
• Most MDR-TB regimens combine a fluoroquinolone with an aminoglycoside (streptomycin, kanamycin, amikacin) or capreomycin 1

Shorter All-Oral BPaLM Regimen (6 Months)

For eligible MDR/RR-TB patients, the 6-month BPaLM regimen (bedaquiline, pretomanid, linezolid, moxifloxacin) represents the preferred treatment option. 4

Eligibility criteria include: 1, 4

• No previous exposure to second-line TB drugs for >1 month
• No fluoroquinolone resistance on drug susceptibility testing
• Absence of extensive pulmonary disease (cavities) or severe extrapulmonary TB (spinal/CNS/miliary)
• Not pregnant
• Age >6 years

Regimen composition: 4

• Bedaquiline (daily for 2 weeks, then thrice weekly for 22 weeks)
• Pretomanid (daily)
• Linezolid (daily)
• Moxifloxacin (daily)

Longer Individualized Regimens (15-24 Months)

When the shorter regimen is contraindicated, construct a longer regimen using at least 5 effective drugs, prioritizing Group A agents (fluoroquinolone, bedaquiline, linezolid). 1, 4

Building the regimen systematically: 1

• Group A (use all three if possible): Levofloxacin OR moxifloxacin + bedaquiline + linezolid
• Group B (add to reach 5 drugs): Clofazimine + cycloserine OR terizidone
• Group C (if needed): Ethambutol, delamanid, pyrazinamide, carbapenems (imipenem-cilastatin or meropenem with amoxicillin/clavulanate), amikacin, ethionamide/prothionamide, or p-aminosalicylic acid

Treatment duration: 1

• 24 months after culture conversion for HIV-positive patients with MDR-TB
• 20-24 months total duration for most MDR-TB cases 5
• Post-treatment monitoring every 4 months for 24 months to detect relapse 1

Isoniazid-Resistant, Rifampin-Susceptible TB

Add a later-generation fluoroquinolone (levofloxacin or moxifloxacin) to a 6-month regimen of daily rifampin, ethambutol, and pyrazinamide. 1, 6, 5

Alternative approach for selected situations (noncavitary, lower-burden disease, or pyrazinamide toxicity): 1

• Fluoroquinolone + rifampin + ethambutol for 6 months
• Pyrazinamide only for the first 2 months

Critical Caveats and Pitfalls

Avoid Older Fluoroquinolones

Never use ciprofloxacin or older fluoroquinolones for TB treatment—they result in higher relapse rates, longer time to sputum culture conversion, and treatment failure. 2, 3

Cross-Resistance Considerations

• Cross-resistance between ofloxacin and moxifloxacin is incomplete (approximately 81% in European data, as low as 7% in some settings) 1
• Always obtain drug susceptibility testing for fluoroquinolones before initiating treatment 1, 7

Resistance Development

Fluoroquinolone resistance is rising globally and defines extensively drug-resistant TB (XDR-TB). 7, 8

• Inappropriate use of fluoroquinolones for other infections in TB patients can select for resistance 7
• Always use directly observed therapy (DOT) for MDR-TB to prevent resistance development 1, 6

Adverse Event Monitoring

Implement active drug safety monitoring (aDSM) for all MDR-TB patients, particularly monitoring for: 1

• QTc prolongation (especially with moxifloxacin + bedaquiline + clofazimine combinations)
• Tendon rupture and arthropathy
• Peripheral neuropathy (when combined with linezolid)
• Hepatotoxicity

Special Populations

For HIV co-infected patients: 6, 4

• Extend treatment to at least 9 months and for at least 6 months beyond documented culture conversion
• Carefully manage drug interactions between antiretrovirals and fluoroquinolones

For pregnant women: 1

• Fluoroquinolones can be used when benefits outweigh risks in MDR-TB
• Avoid aminoglycosides entirely (contraindicated due to fetal toxicity)

Treatment Monitoring

Monthly sputum cultures are mandatory to monitor treatment response. 4

All MDR-TB cases should be discussed at a TB consilium (local, regional, or national expert panel) for treatment optimization. 1