What are the guidelines for treating pulmonary tuberculosis (TB) with first-line and second-line medications?

Guidelines for Treating Pulmonary Tuberculosis with First-line and Second-line Medications

For drug-susceptible pulmonary tuberculosis, the standard first-line treatment regimen is a 6-month course consisting of isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months (intensive phase), followed by isoniazid and rifampin for 4 months (continuation phase). 1, 2

First-line Treatment for Drug-Susceptible TB

Initial Phase (First 2 Months)

• Four-drug regimen including: 1
  • Isoniazid (INH): 5 mg/kg daily (max 300 mg) 2
  • Rifampin (RIF): 10 mg/kg daily (max 600 mg) 1
  • Pyrazinamide (PZA): 15-30 mg/kg daily (max 2 g) 3
  • Ethambutol (EMB): 15-25 mg/kg daily 1

Continuation Phase (Next 4 Months)

• Two-drug regimen including: 1
  • Isoniazid (INH): 5 mg/kg daily (max 300 mg)
  • Rifampin (RIF): 10 mg/kg daily (max 600 mg)

Administration Options

• Daily dosing is strongly recommended 1
• Alternative dosing schedules include: 1
  • 5 days per week under directly observed therapy (DOT)
  • Twice weekly under DOT (not recommended for HIV-infected patients or those with smear-positive/cavitary disease) 1
  • Three times weekly under DOT 1

Special Considerations

• Ethambutol may be discontinued if susceptibility to isoniazid and rifampin is confirmed 1
• For patients with cavitary disease and positive cultures after 2 months of treatment, the continuation phase should be extended to 7 months (total 9 months of therapy) 1
• For culture-negative, smear-negative pulmonary TB, a 4-month regimen may be adequate (2 months of HRZE followed by 2 months of HR) 1

Treatment of Drug-Resistant TB

Isoniazid-Resistant TB

• Add a later-generation fluoroquinolone (levofloxacin or moxifloxacin) to a 6-month regimen of daily rifampin, ethambutol, and pyrazinamide 1
• Pyrazinamide may be discontinued after 2 months in cases of noncavitary disease or if toxicity develops 1

Multidrug-Resistant TB (MDR-TB)

• MDR-TB is defined as resistance to at least isoniazid and rifampin 1
• Treatment should be individualized based on drug susceptibility testing 1
• WHO recommends building a regimen using the following drug classification: 1

Group A (include all three drugs if possible):

• Levofloxacin or moxifloxacin
• Bedaquiline
• Linezolid

Group B (add one or both):

• Clofazimine
• Cycloserine or terizidone

Group C (add when drugs from Groups A and B cannot be used):

• Ethambutol
• Delamanid
• Pyrazinamide
• Imipenem-cilastatin or meropenem (with amoxicillin-clavulanate)
• Amikacin or streptomycin
• Ethionamide or prothionamide
• p-aminosalicylic acid

Treatment Duration for MDR-TB

• Standard duration for individualized longer regimens is 18 months 1
• Shorter all-oral bedaquiline-containing regimen (9-12 months) may be used for eligible patients without extensive disease, prior exposure to second-line drugs, or fluoroquinolone resistance 1

Not Recommended for MDR-TB Regimens

• Amoxicillin-clavulanate (except when used with carbapenems) 1
• Macrolides (azithromycin and clarithromycin) 1
• Kanamycin and capreomycin 1

Special Populations

HIV Co-infection

• Same drug regimen as HIV-negative patients, but may require longer treatment duration 1, 2
• Close monitoring of treatment response is essential 1
• Therapeutic drug monitoring may be necessary due to potential malabsorption issues 1

Pregnancy

• Streptomycin should be avoided (risk of congenital deafness) 2
• Pyrazinamide is generally not recommended due to insufficient teratogenicity data 2
• Initial regimen should consist of isoniazid and rifampin, with ethambutol added if primary isoniazid resistance is likely 2

Children

• Similar regimen as adults with appropriate dose adjustments 2
• Ethambutol should be used with caution in children whose visual acuity cannot be monitored 2

Monitoring and Follow-up

• Bacteriological monitoring with sputum smears and cultures is essential 1
• Persistent positive smears or cultures at or after 3 months should prompt reevaluation 1
• Drug susceptibility testing should be performed on initial isolates from all patients 2
• Never add a single drug to a failing regimen to prevent development of additional resistance 1

Common Pitfalls and Caveats

• Inadequate initial regimen (fewer than 4 drugs) when drug resistance is possible 1
• Poor adherence leading to treatment failure and drug resistance 2
• Failure to adjust treatment based on drug susceptibility results 1
• Adding a single drug to a failing regimen (always add at least 2 new drugs) 1
• Inadequate treatment duration, especially for cavitary disease 1
• Overlooking potential drug interactions, particularly with antiretrovirals in HIV co-infected patients 1