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Drugs for Tuberculosis

organism is susceptible (e.g., pyrazinamide plus either ethambutol or a fluoroquinolone for 9-12 months) have been used, but are poorly tolerated, can be hepa- totoxic and are of uncertain efficacy. 18,19

Duration of Continuation Therapy1

Sputum culture


taken at 2 mos


Cavity on Chest



Extensively drug-resistant TB (XDRTB), now defined as isolates with resistance not only to isoniazid and rifampin but also to any fluoroquinolone and either capreomycin, kanamycin or amikacin (see table on page 18), is an increasing problem worldwide; there are no data-based recommendations for treatment of latent TB following exposure to XDRTB.20-22

Medical Letter consultants recommend that treatment of patients with drug-resistant latent TB be provided by or in collaboration with a clinician experienced in treatment of these infections. Whatever treatment is chosen, such patients should be observed for up to 2 years following exposure.





Negative Positive



Yes Yes

4 4 4

7 4 7

INH = Isoniazid; RIF = rifampin; RPT = rifapentine

  • 1.

    For treatment of drug-susceptible disease after two months of initial therapy.

  • 2.

    Always 7 months for patients who could not take pyrazinamide as part of the initial regimen. Can be shortened to 2 months in non-HIV patients with culture-negative pulmonary TB.

  • 3.

    RPT is a treatment option only for non-pregnant, HIV-negative adults without cavitary or extrapulmonary disease who are smear-negative at 2 months.

  • 4.

    If the culture is positive and the patient is taking INH/RPT, some Medical Letter consultants would switch to INH/RIF.


risk factors, and for those who could not take pyrazi- namide as part of the initial regimen, the continuation phase is extended to 7 months.

All initial isolates of M. tuberculosis should be tested for antimicrobial susceptibility, but results generally do not become available for at least 2-4 weeks. Standard treatment of active TB includes a 2-month initial phase and a continuation phase of either 4 or 7 months, depending on the presence or absence of cav- itary disease at the time of diagnosis and the results of sputum cultures taken at 2 months (see table). Patients should be monitored monthly to assess for adverse reactions, adherence and response to treatment. Medical Letter consultants recommend that patients on self-administered therapy receive no more than a 1- month supply of medication at each visit. 23

Initial Therapy – Until susceptibility results are avail- able, empiric initial treatment should consist of a 4- drug regimen of isoniazid, rifampin, pyrazinamide and ethambutol.24 Patients in areas with low rates of drug- resistant TB who cannot take pyrazinamide, such as those who have severe liver disease or gout, should receive empiric initial therapy with isoniazid, rifampin and ethambutol.

When TB disease proves to be caused by a fully sus- ceptible strain, the initial phase of treatment should consist of isoniazid, rifampin and pyrazinamide for 2 months.

Continuation Therapy – Two factors increase the risk of treatment failure and relapse: cavitary disease at presentation and a positive sputum culture taken at 2 months. For patients with one or no risk factors, the continuation phase of treatment should be with isoni- azid and rifampin for 4 months. For patients with both

For selected patients with neither cavitary disease nor a positive smear after 2 months of therapy, the long-act- ing rifamycin rifapentine, given once-weekly by DOT is an additional option for continuation therapy. Rifapentine should not be used if the patient has extra- pulmonary TB or co-infection with HIV, is younger than 12 years of age or pregnant, or if drug susceptibil- ity is unknown. If the culture taken at 2 months proves to be positive and rifapentine is being used, some Medical Letter consultants would switch to rifampin. 24

If sputum cultures remain positive after 4 months of treatment, nonadherence to treatment or infection with drug-resistant TB must be considered. Only after these are excluded should other causes (e.g., malabsorption) be considered as possible explanations of poor response. Treatment duration should be prolonged in such patients.

TB osteomyelitis is usually treated for 6-9 months. Tuberculous meningitis is usually treated for a total of 9-12 months. Addition of a corticosteroid for 1-2 months is recommended for tuberculous pericarditis or meningitis. 25

Culture-Negative TB – Patients with pulmonary dis- ease who have no positive cultures for M. tuberculosis before treatment and after 2 months of therapy have “culture-negative TB”; in these patients, the continua- tion phase with isoniazid and rifampin can generally be shortened to 2 months. Exceptions are patients with extrapulmonary TB or those co-infected with HIV, who should be treated for 6 months or longer.

Treatment Guidelines from The Medical Letter 17

Vol. 5

(Issue 55)

March 2007

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