What is the treatment protocol for the Tulane extended regimen?

Tulane Extended Regimen for Drug-Resistant Tuberculosis

The Tulane extended regimen for drug-resistant tuberculosis consists of a 4-6 month intensive phase with bedaquiline (6 months), fluoroquinolone, clofazimine, pyrazinamide, ethambutol, high-dose isoniazid, and either ethionamide or linezolid (2 months), followed by a 5-month continuation phase with fluoroquinolone, clofazimine, pyrazinamide, and ethambutol. 1

Regimen Variations

There are two main variations of the Tulane extended regimen:

1. Ethionamide variation:

   • Intensive phase (4-6 months): Bedaquiline (6 months) + Fluoroquinolone + Clofazimine + Pyrazinamide + Ethambutol + High-dose isoniazid + Ethionamide
   • Continuation phase (5 months): Fluoroquinolone + Clofazimine + Pyrazinamide + Ethambutol

2. Linezolid variation:

   • Intensive phase (4-6 months): Bedaquiline (6 months) + Linezolid (2 months) + Fluoroquinolone + Clofazimine + Pyrazinamide + Ethambutol + High-dose isoniazid
   • Continuation phase (5 months): Fluoroquinolone + Clofazimine + Pyrazinamide + Ethambutol

Duration Considerations

• Standard duration: 9 months total (4 months intensive + 5 months continuation)
• Extended duration: 11 months total (6 months intensive + 5 months continuation)
• Extension criteria: The intensive phase may be extended to 6 months if bacteriological conversion is not seen at the end of the fourth month of treatment 1

Special Population Considerations

• Children: The 9-month all-oral regimen can be used in children of all ages, including those below 6 years of age 1
• Pregnant/lactating women: The linezolid variation is recommended instead of the ethionamide variation due to contraindication of ethionamide in pregnancy 1

Fluoroquinolone Selection

• Both levofloxacin and moxifloxacin have shown similar efficacy for treating drug-resistant TB
• Levofloxacin is often preferred due to moxifloxacin's higher potential for cardiotoxicity
• However, levofloxacin has been associated with musculoskeletal disorders in pediatric populations 1

Indications and Contraindications

Indications

• Preferred treatment option for patients with drug-resistant TB without previous exposure to second-line treatment (including bedaquiline)

Contraindications

• Extensive pulmonary disease
• Severe extrapulmonary TB
• CNS TB
• Military TB
• Osteoarticular TB
• These conditions require longer treatment regimens 1

Decision Algorithm

1. Assess eligibility: Confirm drug-resistant TB without previous exposure to second-line drugs
2. Evaluate extent of disease: Rule out extensive pulmonary disease, severe extrapulmonary TB, CNS, military, or osteoarticular TB
3. Select variation based on patient characteristics:
   • For pregnant/lactating women: Choose linezolid variation
   • For non-pregnant adults: Either variation is appropriate
4. Monitor response: Evaluate bacteriological conversion at month 4
5. Adjust duration: If no conversion by month 4, extend intensive phase to 6 months

Monitoring

• Regular sputum cultures to assess bacteriological conversion
• Monitor for adverse effects of individual drugs, particularly:
  • QT prolongation with bedaquiline and fluoroquinolones
  • Peripheral neuropathy with linezolid
  • Optic neuritis with ethambutol
  • Hepatotoxicity with pyrazinamide and ethionamide

The Tulane extended regimen represents an important advancement in the treatment of drug-resistant tuberculosis, offering a shorter 9-11 month treatment course compared to the traditional 18-20 month regimens while maintaining efficacy for appropriate patients.