What class of therapy should be started for a patient with suspected tuberculosis (TB) and a positive Purified Protein Derivative (PPD) test?

Antituberculosis Therapy (Four-Drug Regimen)

This patient should be started immediately on a four-drug antituberculosis regimen consisting of isoniazid, rifampin, pyrazinamide, and ethambutol (or streptomycin) for the initial 2-month intensive phase, followed by isoniazid and rifampin for 4 months. 1

Clinical Presentation Supports Active TB Diagnosis

This elderly patient presents with classic features of active pulmonary tuberculosis:

• Prolonged respiratory symptoms (4 weeks of cough with hemoptysis and pleuritic chest pain) 1
• Positive PPD test (11 mm induration, which exceeds the 5 mm threshold for active TB consideration) 1
• Radiographic findings consistent with TB (mediastinal lymphadenopathy, lower lobe lesions, and pleural effusions) 1

The combination of clinical symptoms, positive tuberculin skin test, and characteristic chest X-ray findings provides strong evidence to initiate empiric treatment immediately, even before culture results are available. 1

Standard Four-Drug Initial Regimen

Initial Intensive Phase (First 2 Months)

The four-drug regimen is mandatory in this case because:

• Most areas in the United States have isoniazid resistance rates >4%, making four-drug therapy the standard 1
• The patient's drug susceptibility pattern is unknown at presentation 1
• Using four drugs ensures at least two effective agents are present, preventing selection of resistant organisms 1

Specific drug combination:

• Isoniazid (INH)
• Rifampin (RIF)
• Pyrazinamide (PZA)
• Ethambutol (EMB) or Streptomycin (SM) 1, 2, 3

The fourth drug (ethambutol or streptomycin) can be discontinued once drug susceptibility testing confirms the organism is susceptible to isoniazid, rifampin, and pyrazinamide. 1

Continuation Phase (Months 3-6)

Standard duration is 4 additional months with isoniazid and rifampin only, for a total treatment duration of 6 months. 1

However, extend the continuation phase to 7 months (total 9 months) if:

• Cavitary disease is present on initial chest radiograph AND sputum culture remains positive after 2 months of treatment 1
• The initial phase did not include pyrazinamide 1

Administration Schedule Options

Daily therapy is preferred initially, but directly observed therapy (DOT) with intermittent dosing is acceptable:

• Daily for 2 months, then daily or twice weekly for 4 months 1
• Daily for 2 weeks, then twice weekly for 6 weeks, followed by twice weekly for 4 months 1
• Three times weekly throughout (only with DOT) 1

Critical Monitoring Requirements

Baseline Assessment

• Obtain sputum for acid-fast bacilli smear and mycobacterial culture with drug susceptibility testing before starting treatment 1
• Baseline liver function tests, renal function, and complete blood count 1
• Visual acuity and color discrimination testing (baseline for ethambutol monitoring) 1

During Treatment

• Sputum monitoring: Repeat smear and culture after 2 months of treatment 1
• Monthly clinical evaluations to assess adherence and identify adverse effects 1
• Liver function monitoring: Check transaminases twice weekly during the first 2 weeks, then every 2 weeks during the first 2 months, then monthly 4
• Visual monitoring: Monthly questioning about visual disturbances and testing of visual acuity/color discrimination for patients on ethambutol 1

Important Caveats and Pitfalls

Hepatotoxicity Risk

Stop all hepatotoxic drugs immediately if transaminases rise >3 times the upper limit of normal. 4

• Two patterns of liver injury can occur: early (within 15 days, likely rifampin-enhanced isoniazid toxicity) with good prognosis, or late (>1 month, possibly pyrazinamide-related) with poor prognosis 4
• After transaminases normalize, isoniazid can be reintroduced at low doses without rifampin, but do not reintroduce pyrazinamide due to risk of severe recurrent hepatitis 4

Drug Resistance Considerations

If cultures remain positive after 3 months or clinical deterioration occurs, repeat drug susceptibility testing immediately and consider multidrug-resistant TB. 1

Respiratory Isolation

Place the patient in respiratory isolation immediately until she meets criteria for being noninfectious: receiving effective therapy, clinically improving, and has three consecutive negative sputum smears collected on different days. 1

Special Population Considerations

If this patient has HIV co-infection (should be tested), treatment duration should be extended to at least 9 months and 6 months after sputum conversion. 1 Additionally, avoid once-weekly continuation regimens in HIV-infected patients due to high failure rates with rifamycin resistance. 1