What is the treatment for pulmonary tuberculosis in a patient with potential drug-resistant strains or underlying medical conditions, such as HIV/AIDS?

Treatment of Pulmonary Tuberculosis

For drug-susceptible pulmonary tuberculosis, treat with a 6-month daily regimen consisting of isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB) for 2 months, followed by INH and RIF for 4 months. 1

Standard Treatment Regimen for Drug-Susceptible Disease

Intensive Phase (First 2 Months)

• Four-drug combination: INH, RIF, PZA, and EMB given daily 1, 2, 3
• Dosing:
  • INH: 5 mg/kg up to 300 mg daily 4
  • RIF: 10 mg/kg up to 600 mg daily 5, 3
  • PZA: 15-30 mg/kg daily (weight-based dosing: 1000-2000 mg for adults 40-90 kg) 1, 5, 2
  • EMB: 15-20 mg/kg daily (weight-based dosing: 800-1600 mg for adults 40-90 kg) 1, 5

Continuation Phase (Next 4 Months)

• Two-drug combination: INH and RIF given daily 1
• Same dosing as intensive phase for INH and RIF 4, 3

Critical Implementation Points

• Daily therapy is strongly recommended over intermittent dosing for optimal treatment efficacy 5
• Directly observed therapy (DOT) should be used for all patients to ensure adherence and prevent resistance 1, 4, 6
• Include EMB in the initial regimen until drug susceptibility results are available, unless primary INH resistance is documented to be less than 4% in the community 1, 6

Special Populations and Modifications

HIV-Infected Patients

For HIV-infected patients receiving antiretroviral therapy (ART), use the standard 6-month daily regimen (2 months INH/RIF/PZA/EMB, then 4 months INH/RIF). 1

For HIV-infected patients NOT receiving ART, extend the continuation phase to 7 months (total 9 months of therapy). 1

Key HIV-Specific Considerations:

• Never use intermittent (twice-weekly or thrice-weekly) regimens in HIV-infected patients due to high relapse rates (up to 16.7%) and emergence of rifamycin resistance 1
• All relapses in one study occurred in patients with CD4 counts <100 cells/μL 1
• ART should be initiated in conjunction with daily anti-tuberculosis medications to reduce mortality and AIDS-defining illnesses 1
• Monitor for drug interactions between rifamycins and protease inhibitors/NNRTIs; consider rifabutin as alternative to rifampin when using certain antiretrovirals 1
• Rifampin's CYP450 induction continues for 2 weeks after discontinuation, requiring careful timing when starting protease inhibitors or NNRTIs 1

Drug-Resistant Tuberculosis

Isoniazid-Resistant TB:

Add a later-generation fluoroquinolone (levofloxacin or moxifloxacin) to a 6-month regimen of daily RIF, EMB, and PZA. 7, 5

Multidrug-Resistant TB (MDR-TB: resistant to at least INH and RIF):

For MDR/RR-TB, use the 6-month BPaLM regimen consisting of bedaquiline, pretomanid, linezolid, and moxifloxacin. 8

• This regimen is indicated when there is no documented resistance to fluoroquinolones or bedaquiline 8
• Fluoroquinolones (levofloxacin/moxifloxacin) are Group A highest priority drugs and should be included in all MDR-TB regimens 7, 8
• Include at least 5 effective drugs during the intensive phase 5
• Ethambutol should only be included when more effective drugs cannot be assembled to achieve five effective drugs 7
• Treatment duration for MDR-TB is typically 20-24 months when using longer individualized regimens 5

Pregnancy:

• Avoid pyrazinamide due to insufficient teratogenicity data 5, 4
• Never use streptomycin as it causes congenital deafness 4, 6
• Use INH, RIF, and EMB as the initial regimen 5, 4

Extrapulmonary TB:

• Use the same 6-month regimen for most extrapulmonary sites 6
• Extend treatment to 9-12 months for:
  • Tuberculous meningitis 1, 9
  • Bone, joint, and spinal tuberculosis 1, 9
  • Miliary tuberculosis in children 6

Monitoring and Follow-Up

Treatment Response Monitoring:

• Obtain sputum cultures monthly until negative to monitor treatment response 8, 4
• Patients should demonstrate sputum conversion within 3 months 1
• Perform drug susceptibility testing on all initial isolates 4, 3, 9

Toxicity Monitoring:

• Teach patients to recognize and immediately report symptoms of hepatotoxicity: loss of appetite, nausea, vomiting, jaundice, malaise, unexplained fever >3 days, or abdominal tenderness 1, 5
• Monitor monthly for ethambutol ocular toxicity (visual impairment); discontinue immediately if detected 7, 5
• Regular liver function monitoring is essential, especially with pyrazinamide 5
• Consider pyridoxine 50 mg daily with INH for patients with diabetes, uremia, alcoholism, malnutrition, or pregnancy 1

Common Pitfalls and Caveats

Resistance Development:

• The primary cause of drug-resistant TB is patient non-adherence 4
• Intermittent regimens in HIV-infected patients lead to unacceptably high relapse rates and resistance emergence 1
• Lower plasma drug concentrations are key risk factors for acquiring rifamycin resistance 1

Treatment Failure:

• If cultures remain positive after 3 months, evaluate for non-adherence and drug-resistant organisms 1
• Therapeutic drug monitoring may be necessary if poor response is suspected due to under-dosing or malabsorption 5
• In HIV-infected patients with advanced disease, screen antimycobacterial drug levels to prevent emergence of MDR-TB 4

Reinfection vs. Relapse:

• In high-transmission settings (high TB prevalence areas, prisons, hospitals with inadequate infection control), recurrence may be due to reinfection rather than relapse 1
• In areas where reinfection is likely, secondary preventive therapy with INH may be justified after treatment completion 1