What is the recommended workup and treatment for a patient with suspected active pulmonary tuberculosis (historically called consumption)?

Management of Suspected Active Pulmonary Tuberculosis

Start standard four-drug therapy immediately with isoniazid, rifampin, pyrazinamide, and ethambutol as soon as active pulmonary tuberculosis is suspected—do not wait for culture confirmation. 1, 2, 3

Immediate Diagnostic Workup

Sputum Collection and Testing

• Collect three sputum specimens (8-24 hours apart, with at least one early morning sample) for AFB smear, culture, and drug susceptibility testing before initiating therapy 3
• Use sputum induction with hypertonic saline if the patient cannot produce adequate specimens 3
• In children unable to produce sputum, obtain specimens via early morning gastric aspiration, bronchoalveolar lavage, or biopsy 1

Additional Baseline Assessment

• Obtain chest radiograph to assess for cavitation, which affects treatment duration 3
• Perform baseline liver function tests (AST, ALT, bilirubin) due to hepatotoxicity risk from isoniazid, rifampin, and pyrazinamide 2
• Offer HIV counseling and testing to all patients, as HIV status determines treatment duration and monitoring intensity 1
• Check baseline visual acuity and color discrimination if ethambutol will be used 4

Standard Treatment Regimen

Initial Intensive Phase (2 months)

• Isoniazid: 5 mg/kg daily (maximum 300 mg) 3, 5
• Rifampin: 10 mg/kg daily (maximum 600 mg) 3
• Pyrazinamide: 25-35 mg/kg daily 3, 4
• Ethambutol: 15-20 mg/kg daily 1, 3

The four-drug regimen protects against unrecognized drug resistance while awaiting susceptibility results. 4 Ethambutol can be omitted only if primary isoniazid resistance is documented to be less than 4% in the community AND the patient has no prior TB treatment, no exposure to drug-resistant cases, and is not from a high-prevalence country. 5

Continuation Phase (4 months)

• Isoniazid: 5 mg/kg daily (maximum 300 mg) 3
• Rifampin: 10 mg/kg daily (maximum 600 mg) 3

This yields a total treatment duration of 6 months for drug-susceptible TB. 1, 2, 3

Treatment Duration Modifications

Extend to 9 Months Total If:

• Cavitation present on initial chest radiograph AND positive sputum culture at 2 months of treatment 3
• HIV-positive patients (minimum 9 months and at least 6 months beyond documented culture conversion with three negative cultures) 3
• Tuberculous meningitis or disseminated tuberculosis (9-12 months recommended) 1

Shorten to 4 Months Total If:

• Culture-negative pulmonary TB with clinical or radiographic improvement at 2 months in HIV-negative patients 1, 3

Directly Observed Therapy

Implement directly observed therapy (DOT) for all patients—this is the single most important factor determining treatment success. 4 A healthcare worker must observe the patient swallow each dose to ensure compliance and prevent emergence of drug resistance. 2, 3 Intermittent therapy (twice or thrice weekly) may be used but ONLY with directly observed administration. 3

Monitoring During Treatment

Clinical and Bacteriologic Monitoring

• Assess patients at least twice monthly for symptoms and by smear until asymptomatic and smear-negative 3
• Obtain monthly sputum cultures until two consecutive specimens are negative 2, 3
• Approximately 80% of patients should have negative cultures at 2 months 4
• Monitor visual acuity monthly in patients receiving ethambutol 4

Laboratory Monitoring

• Evaluate patients monthly for drug toxicity, questioning specifically about symptoms even if no problems are apparent 3
• Monitor liver function tests weekly for the first 2 weeks if hepatotoxicity risk factors are present (pre-existing liver disease, alcohol use, HIV infection, pregnancy) 3

Special Populations

HIV-Infected Patients

• Start antiretroviral therapy within the first 8 weeks of TB treatment 4
• Use rifampin-based regimens with caution if patient is on protease inhibitors or non-nucleoside reverse transcriptase inhibitors due to drug interactions 1
• Treat for minimum 9 months total 1, 3
• Be alert for immune reconstitution inflammatory syndrome (paradoxical worsening after starting treatment) 6

Pregnant Women

• Use standard four-drug regimen (isoniazid, rifampin, pyrazinamide, ethambutol) 1
• Avoid streptomycin due to fetal ototoxicity 6
• Add prophylactic pyridoxine 10-25 mg daily to prevent peripheral neuropathy 6

Children

• Use same regimens as adults with appropriately adjusted doses 1, 5
• Ethambutol can be used safely at 15-20 mg/kg daily even in children too young for routine eye testing when drug resistance is suspected 1
• Extend treatment to 9-12 months for disseminated tuberculosis and tuberculous meningitis 1
• Rely on drug susceptibility tests from the presumed source case to guide therapy when isolating M. tuberculosis from the child is difficult 1

Renal Insufficiency

• Administer all drugs after hemodialysis to facilitate DOT and avoid premature drug removal 1, 4
• Adjust ethambutol dosing for creatinine clearance to prevent optic toxicity 4

Liver Disease

• If baseline AST is more than 3 times normal, consider alternative regimens such as rifampin, ethambutol, and pyrazinamide for 6 months (avoiding isoniazid) OR isoniazid and rifampin for 9 months (avoiding pyrazinamide) 1
• Monitor liver function tests twice weekly during the first 2 weeks 4

Treatment Failure and Drug Resistance

Positive Cultures After 2 Months

• Evaluate for nonadherence (most common cause), extensive cavitary disease, drug resistance, or malabsorption 4
• If cultures remain positive after 4 months of appropriate therapy, this indicates treatment failure 4
• Add at least two new drugs to which susceptibility can be inferred 4

Multidrug-Resistant TB (MDR-TB)

• Refer to specialized units with facilities for quality-controlled drug susceptibility testing 6
• Use shorter all-oral bedaquiline-containing regimens of 9-12 months for eligible MDR/rifampin-resistant TB patients 4
• Treatment must be individualized based on susceptibility testing 5

Critical Pitfalls to Avoid

• Never initiate single-drug therapy or add a single drug to a failing regimen—this rapidly leads to drug resistance 2, 3
• Do not delay treatment while awaiting culture results if clinical suspicion is high—this leads to disease progression and continued transmission 3
• Do not use fluoroquinolones for empiric pneumonia coverage in patients with suspected TB, as this rapidly creates TB drug resistance 4
• Do not discontinue therapy without consulting a TB specialist if drug-induced adverse effects are suspected 2
• Avoid hepatotoxic medications including acetaminophen and alcohol during treatment 4
• Do not use fixed-dose combinations in patients weighing >90 kg, as pyrazinamide dosing may be insufficient 4

Isolation and Infection Control

• Place patients in respiratory isolation (preferably negative pressure room) immediately upon suspicion of active TB 1
• Continue isolation until patient is on appropriate treatment, clinically improving, and has three consecutive negative AFB smears on different days 1
• Infectiousness declines rapidly (within days) after initiation of effective treatment 1