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 recurrences in one trial occurred in patients with CD4 counts <100 cells/μL 1
• ART should be initiated in conjunction with daily antituberculosis medications to reduce mortality and AIDS-defining illnesses 1
• Drug interactions between rifamycins and protease inhibitors/NNRTIs require careful management 1
• Consider rifabutin instead of rifampin when using 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):

For MDR/RR-TB, use the 6-month BPaLM regimen (bedaquiline, pretomanid, linezolid, moxifloxacin) when there is no documented resistance to fluoroquinolones or bedaquiline. 8

• Longer individualized oral regimens (15-24 months) are required when resistance to fluoroquinolones or bedaquiline exists 8
• Include at least 5 effective drugs with core agents: bedaquiline, later-generation fluoroquinolone, and linezolid 8
• Strongly recommend including a later-generation fluoroquinolone (levofloxacin or moxifloxacin) in all MDR-TB regimens 7
• Ethambutol should only be included when more effective drugs cannot be assembled to achieve five effective drugs 7

Pregnancy

• Avoid pyrazinamide during pregnancy due to insufficient teratogenicity data 5, 4
• Never use streptomycin in pregnancy as it causes congenital deafness 4
• Use INH, RIF, and EMB for initial treatment, extending duration as needed 5, 4

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:

• Instruct patients to report hepatitis symptoms immediately (loss of appetite, nausea, vomiting, jaundice, malaise, fever >3 days, abdominal tenderness) when receiving INH, RIF, or PZA 1, 5
• Monitor monthly for visual impairment when using ethambutol; discontinue 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

Avoiding Treatment Failure:

• Non-adherence is the major cause of drug-resistant tuberculosis - this is why DOT is critical 4, 10
• Intermittent regimens in HIV-infected patients lead to unacceptably high relapse rates and resistance 1
• Lower plasma drug concentrations are key risk factors for acquiring rifamycin resistance 1

Extended Treatment Indications:

• Extend continuation phase for tuberculous meningitis (12 months total), bone/joint/spinal TB (9-12 months), and patients at increased risk of relapse 1, 6
• In areas where reinfection is likely (high TB prevalence settings), consider secondary INH preventive therapy after treatment completion 1

Drug Interactions:

• Rifampin's CYP450 induction effect continues for at least 2 weeks after discontinuation - plan accordingly when starting protease inhibitors or NNRTIs 1
• Patients on methadone require increased methadone dosing when receiving rifampin 1