What are the other uses and indications for Anti-Tuberculosis Treatment (ATT) drugs?

Alternative Uses and Indications for Anti-Tuberculosis Treatment (ATT) Drugs

Anti-tuberculosis drugs have several important applications beyond treating active tuberculosis, including treatment of latent TB infection, drug-resistant TB, and non-tuberculous conditions. While their primary purpose is treating active tuberculosis disease, these medications have proven valuable in various clinical scenarios.

Treatment of Drug-Resistant Tuberculosis

MDR/RR-TB Treatment

• For multidrug-resistant or rifampin-resistant TB, specialized regimens are required:
  • Fluoroquinolones (levofloxacin, moxifloxacin) are recommended as core drugs 1
  • Bedaquiline and delamanid may be included for patients >3 years of age 1
  • Linezolid is recommended as a core second-line medication 1
  • Clofazimine and cycloserine are often included in regimens 1

Isoniazid-Resistant TB

• For isoniazid-resistant TB (but rifampin-sensitive):
  • A later-generation fluoroquinolone should be added to a 6-month regimen of daily rifampin, ethambutol, and pyrazinamide 1
  • Pyrazinamide duration can be shortened to 2 months in selected situations (non-cavitary disease, lower bacterial burden, or pyrazinamide toxicity) 1

Treatment of Latent TB Infection

Contacts of MDR-TB Patients

• Treatment for latent TB infection is recommended for contacts of MDR-TB patients rather than observation alone 1
• Recommended regimen: 6-12 months of a later-generation fluoroquinolone alone or with a second drug, based on drug susceptibility of the source case 1
• Pyrazinamide should not be routinely used as the second drug due to increased toxicity and adverse events 1

Primary and Secondary Chemoprophylaxis

• Primary chemoprophylaxis: Isoniazid 5 mg/kg given to prevent infection in newborn infants of infectious mothers until mother is sputum smear negative (2-3 months) 2
• Secondary chemoprophylaxis: Isoniazid 5 mg/kg for 6 months to prevent disease in infected but asymptomatic individuals 2

Treatment of TB in Special Situations

Elevated Liver Enzymes

• For patients with elevated liver enzymes, non-hepatotoxic drugs can be used:
  • Ethambutol and streptomycin are recommended as they are not hepatotoxic 3
  • Standard dosing for ethambutol is 15-25 mg/kg/day, and for streptomycin is 15 mg/kg/day (maximum 1g/day) 3
  • When liver enzymes normalize, sequential reintroduction of first-line drugs can be attempted, starting with the least hepatotoxic 3

HIV Co-infection

• Standard short-course chemotherapy is indicated in HIV-positive patients 2
• When using protease inhibitors or NNRTIs:
  • Rifabutin can be substituted for rifampin with dose adjustments 1
  • When rifabutin is used with indinavir, nelfinavir, or amprenavir, the daily dose should be decreased from 300 mg to 150 mg 1
  • With efavirenz, the dose of rifabutin should be increased to 450 mg 1

Other Special Populations

• Pregnancy: Rifampin, isoniazid, ethambutol, and pyrazinamide can be used; streptomycin is contraindicated due to ototoxicity to the fetus 2
• Renal failure: Dosages must be adjusted according to creatinine clearance, especially for streptomycin, ethambutol, and isoniazid 2
• Post-renal transplant: Rifampin-containing regimens are avoided as rifampin increases clearance of cyclosporin 2

Non-TB Indications

Meningococcal Carriers

• Rifampin is indicated for the treatment of asymptomatic carriers of Neisseria meningitidis to eliminate meningococci from the nasopharynx 4
• Dosing:
  • Adults: 600 mg rifampin twice daily for two days
  • Pediatric patients ≥1 month: 10 mg/kg (not exceeding 600 mg per dose) every 12 hours for two days
  • Pediatric patients <1 month: 5 mg/kg every 12 hours for two days 4

Important Considerations and Precautions

Drug Interactions

• ATT drugs have significant interactions with antiretroviral medications:
  • Rifamycins induce CYP P450 metabolism, affecting levels of protease inhibitors and NNRTIs 1
  • QT interval prolongation can occur with fluoroquinolones, bedaquiline, delamanid, and clofazimine, especially when combined with certain antiretrovirals 1
  • Nephrotoxicity risk increases when aminoglycosides are combined with tenofovir 1

Overlapping Toxicities

• Mental health changes (depression, psychosis) can occur with cycloserine, isoniazid, ethionamide, and fluoroquinolones 1
• Peripheral neuropathy is associated with aminoglycosides, linezolid, isoniazid, ethionamide, and cycloserine 1
• Hepatotoxicity is common with isoniazid, pyrazinamide, and ethionamide 1
• Dysglycemia can occur with ethionamide, p-aminosalicylic acid, fluoroquinolones, and linezolid 1

Monitoring Requirements

• For streptomycin: Baseline and monthly audiogram, vestibular testing, Romberg testing, and serum creatinine measurement 1
• For cycloserine: Serum concentration measurements to determine optimum dose and avoid toxicity 1
• For hepatotoxic drugs: Liver function tests at baseline and monthly if underlying liver disease 1

By understanding these alternative uses and special considerations for ATT drugs, clinicians can optimize treatment while minimizing adverse effects in various clinical scenarios beyond standard tuberculosis treatment.