What is the treatment for tuberculosis?

Treatment of Tuberculosis

Drug-Susceptible Pulmonary Tuberculosis

The standard treatment for drug-susceptible tuberculosis is a 6-month regimen: 2 months of isoniazid, rifampin, pyrazinamide, and ethambutol (2HRZE), followed by 4 months of isoniazid and rifampin (4HR). 1, 2

Initial Intensive Phase (First 2 Months)

• Administer four drugs daily: isoniazid (H), rifampin (R), pyrazinamide (Z), and ethambutol (E) 1
• Daily dosing is strongly recommended over intermittent dosing during this phase 1
• Fixed-dose combinations provide more convenient administration and may improve adherence 1
• Ethambutol can only be omitted if primary isoniazid resistance is documented to be less than 4% in the community AND the patient has no previous TB treatment, is not from a high-prevalence drug-resistance country, and has no known exposure to drug-resistant cases 1

Continuation Phase (Months 3-6)

• Continue isoniazid and rifampin for 4 additional months 1, 2
• The continuation phase should only begin after confirming susceptibility to isoniazid and rifampin 3
• After initial 2 weeks of daily therapy, can transition to thrice-weekly or twice-weekly directly observed therapy (DOT) in selected low-risk patients 1

Treatment Monitoring

• Baseline evaluation must include sputum smear and culture, drug susceptibility testing, chest radiograph, HIV testing, and hepatitis B/C screening for patients with risk factors 1
• Obtain monthly sputum cultures until 2 consecutive specimens are negative 1
• Repeat drug susceptibility testing if patient remains culture-positive after 3 months of treatment 1
• Conduct monthly assessments of weight, adherence, symptom improvement, and adverse effects 1
• Patients not responding after 3 months require reevaluation 3

Directly Observed Therapy

• DOT is the central element of successful TB management and should be implemented whenever possible 3
• Patient-centered approaches should be individualized based on clinical and social history, using measures such as video-observed treatment, treatment supporters, and financial/social support 3

Special Populations and Situations

HIV Co-infection

• The same 6-month regimen applies 1
• Critically important to assess clinical and bacteriologic response 1
• Consider extending treatment to at least 9 months and for at least 6 months beyond documented culture conversion 1

Pregnant Women

• Initial regimen should include isoniazid, rifampin, and ethambutol 1
• Pyrazinamide should not be routinely recommended due to inadequate teratogenicity data 1

Treatment Interruptions

• During intensive phase: if interrupted for less than 14 days, continue to complete planned total doses; if interrupted for 14 days or more, restart from the beginning 1
• During continuation phase: decision to restart or continue depends on duration of interruption and patient adherence 1

Drug-Resistant Tuberculosis

Isoniazid-Resistant TB

• Add a later-generation fluoroquinolone (levofloxacin, moxifloxacin, or gatifloxacin) to a 6-month regimen of rifampin, ethambutol, and pyrazinamide 4, 1
• In selected situations (noncavitary and lower burden disease or toxicity from pyrazinamide), the duration of pyrazinamide can be shortened to 2 months 4

Multidrug-Resistant TB (MDR-TB)

Consultation with a TB expert is mandatory, and treatment must be individualized based on drug susceptibility testing 1

Building an MDR-TB Regimen

• Construct a regimen with at least 5 effective drugs 4
• Include bedaquiline in the regimen 4
• Include linezolid in the regimen 4
• Include levofloxacin or moxifloxacin in the regimen 4
• Include clofazimine in the regimen 4
• Include cycloserine or terizidone if needed to compose an effective regimen 4
• Do NOT include kanamycin or capreomycin 4
• Include amikacin or streptomycin when susceptibility to these drugs is confirmed 4
• Include a carbapenem (always to be used with amoxicillin-clavulanic acid) 4
• Do NOT routinely include p-aminosalicylic acid if more effective drugs are available 4

Surgical Management

• Elective partial lung resection (lobectomy or wedge resection) should be considered for adults with MDR-TB receiving antimicrobial therapy when clinical judgement, supported by bacteriological and radiographic data, suggests strong risk of treatment failure or relapse with medical therapy alone 4

Contacts to MDR-TB Patients

• Offer treatment for latent TB infection (LTBI) for contacts to patients with MDR-TB versus observation alone 4
• Use 6 to 12 months of treatment with a later-generation fluoroquinolone alone or with a second drug, based on drug susceptibility of the source-case isolate 4
• Pyrazinamide should not be routinely used as the second drug due to increased toxicity, adverse events, and discontinuations 4

Extrapulmonary Tuberculosis

Peritoneal Tuberculosis

• Peritoneal tuberculosis should be treated with the standard 6-month regimen used for pulmonary tuberculosis: 2HRZE followed by 4HR 3
• Corticosteroids are not routinely indicated for peritoneal tuberculosis 3

Common Pitfalls

• Avoid intermittent therapy with rifampin; doses greater than 600 mg given once or twice weekly result in higher incidence of adverse reactions including flu syndrome, hematopoietic reactions, and renal failure 5
• Patients should be cautioned against intentional or accidental interruption of the daily dosage regimen since rare renal hypersensitivity reactions have been reported when therapy was resumed 5
• Rifampin produces discoloration (yellow, orange, red, brown) of teeth, urine, sweat, sputum, and tears; soft contact lenses may be permanently stained 5
• Rifampin is a potent inducer of drug metabolizing enzymes and might decrease or increase concomitant drug exposure; patients should not take any other medication without medical advice 5