Tuberculosis (TB) Medication

Updated: Oct 01, 2018
  • Author: Thomas E Herchline, MD; Chief Editor: Michael Stuart Bronze, MD  more...
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Medication

Medication Summary

The treatment of tuberculosis (TB) must satisfy the following basic therapeutic principles:

  • Any regimen must use multiple drugs to which Mycobacterium tuberculosis is susceptible

  • The medications must be taken regularly

  • The therapy must continue for a period sufficient to resolve the illness

New cases are initially treated with four drugs: isoniazid, rifampin, pyrazinamide, and either ethambutol or streptomycin. After 2 months, they are then treated with a continuation phase of 4 months with isoniazid and rifampin. Patients requiring retreatment should initially receive at least 5 drugs, including isoniazid, rifampin, pyrazinamide, and at least 2 (preferably 3) new drugs to which the patient has not been exposed. [1]

In three phase III trials, shorter TB treatment regimens were not as effective as standard 6-month regimens. [88, 89, 90, 91, 92] In all of the trials, one of the standard treatment drugs was replaced with a fluoroquinolone. In the first study, ethambutol was replaced with gatifloxacin for 2 months of intensive treatment followed by a 2-month continuation phase. In the shorter regimen group, 21.0% of patients had unfavorable outcomes, compared with 17.2% of patients in the standard regimen group. Rates of recurrence were 14.6% and 7.1% in the two groups, respectively. [89]

The second study involved a 4-month treatment regimen in which moxifloxacin was substituted for isoniazid for 2 months, followed by moxifloxacin and rifapentine twice weekly for 2 months. This shorter regimen was inferior to both a 6-month regimen with moxifloxacin and to a standard 6-month treatment regimen. [90]

In the third study, ethambutol or isoniazid was replaced with moxifloxacin. Favorable outcomes were seen in 85% and 80% of the two moxifloxacin groups, compared with 92% of the standard treatment group. [91]

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Antitubercular agents

Class Summary

The goals of TB treatment are to shorten the clinical course of TB, prevent complications, prevent the development of latency and/or subsequent recurrences, and decrease the likelihood of TB transmission. In patients with latent TB, the goal of therapy is to prevent disease progression.

Isoniazid

This is the drug of choice for use in preventive therapy and the primary drug for use in combination therapy for active TB. It is also used in combination with rifapentine for adults and children aged 2 years or older with latent TB as once-weekly DOT therapy for 12 weeks. Its mechanism of action is not fully known, but isoniazid may inhibit the synthesis of mycolic acid, resulting in disruption of the bacterial cell wall. In patients receiving treatment for active TB, pyridoxine 25-50 mg orally once daily should be coadministered to prevent peripheral neuropathy.

Rifampin (Rifadin)

Rifampin is used in combination with at least 1 other antituberculous drug for the treatment of active TB. It inhibits DNA-dependent RNA polymerase activity in bacterial cells but not in mammalian cells. Cross-resistance may occur.

In most susceptible cases, the patient undergoes 6 months of treatment. Treatment lasts for 9 months if the patient's sputum culture result is still positive after 2 months of therapy.

Pyrazinamide

This is a pyrazine analog of nicotinamide that is either bacteriostatic or bactericidal against M tuberculosis, depending on the concentration of drug attained at the site of infection. Pyrazinamide's mechanism of action is unknown. Administer the drug for the initial 2 months of a 6-month or longer treatment regimen for drug-susceptible TB. Treat drug-resistant TB with individualized regimens.

Ethambutol (Myambutol)

Ethambutol diffuses into actively growing mycobacterial cells (eg, tubercle bacilli). It impairs cell metabolism by inhibiting the synthesis of 1 or more metabolites, which in turn causes cell death. No cross-resistance has been demonstrated.

Mycobacterial resistance is frequent with previous therapy. In such cases, use ethambutol in combination with second-line drugs that have not been previously administered. Administer every 24 hours until permanent bacteriologic conversion and maximal clinical improvement are observed. Absorption is not significantly altered by food.

Adverse effects of ethambutol include optic neuritis, which is usually reversible with discontinuation of the drug. During the period when the patient is on a daily dose of 25 mg/kg, monthly eye exams are recommended.

Streptomycin

Streptomycin sulfate, an aminoglycoside, is used for the treatment of susceptible mycobacterial infections. Use this agent in combination with other antituberculous drugs (eg, isoniazid, ethambutol, rifampin).

Although the total period of treatment for TB is a minimum of 6 months, streptomycin therapy is not commonly used for the full duration of therapy, because of toxicity concerns. The drug is recommended when less potentially hazardous therapeutic agents are ineffective or contraindicated.

Levofloxacin (Levaquin)

Levofloxacin, a second-line antituberculous drug, is used in combination with rifampin and other antituberculous agents in treating most cases of multidrug-resistant TB (MDR-TB). A good safety profile with long-term use among the fluoroquinolones has made levofloxacin the preferred oral agent for treating MDR-TB caused by organisms resistant to first-line drugs. Levofloxacin elicits its action through inhibition of bacterial topoisomerase IV and DNA gyrase, which are required for DNA replication, transcription, repair, and recombination.

Moxifloxacin (Avelox)

Moxifloxacin, a second-line antituberculous drug, inhibits the A subunits of DNA gyrase, resulting in inhibition of bacterial DNA replication and transcription. Moxifloxacin can be used for MDR-TB caused by organisms known or presumed to be sensitive to fluoroquinolones or when first-line drugs cannot be used because of intolerance.

Rifapentine (Priftin)

This agent is used twice weekly as part of a multiple drug regimen for 2 months during the intensive phase of TB treatment, then once weekly for 4 months, along with isoniazid or an appropriate agent for susceptible organisms. It is also indicated for adults and children aged 2 years or older with latent TB in combination with isoniazid as once-weekly therapy for 12 weeks. Rifapentine inhibits DNA-dependent RNA polymerase in susceptible strains of M tuberculosis organisms. It should not be used to treat active tuberculosis in individuals with HIV infection or with positive TB cultures after 2 months of treatment.

Ethionamide (Trecator)

Ethionamide is a second-line drug that is bacteriostatic or bactericidal against M tuberculosis, depending on the concentration of the drug attained at the site of infection. It is recommended if treatment with first-line drugs (isoniazid, rifampin) is unsuccessful. Ethionamide can be used to treat any form of active TB. However, it should be used only with other effective antituberculous agents.

Amikacin

Amikacin is a second-line drug used to treat patients with MDR-TB or those who do not tolerate first-line therapies. This agent irreversibly binds to the 30S subunit of bacterial ribosomes, blocking the recognition step in protein synthesis and causing growth inhibition.

Cycloserine

Cycloserine, a second-line TB drug, inhibits cell wall synthesis in susceptible strains of gram-positive and gram-negative bacteria and in M tuberculosis. It is a structural analogue of D-alanine, which antagonizes the role of D-alanine in bacterial cell wall synthesis, inhibiting growth. Like all antituberculosis drugs, cycloserine should be administered in conjunction with other effective TB drugs and not as the sole therapeutic agent

Capreomycin (Capastat)

Capreomycin, which is obtained from Streptomyces capreolus, is a second-line drug that is coadministered with other antituberculous agents in pulmonary infections caused by capreomycin-susceptible strains of M tuberculosis. Capreomycin is used only when first-line agents (eg, isoniazid, rifampin) have been ineffective or cannot be used because of toxicity or the presence of resistant tubercle bacilli.

Rifabutin (Mycobutin)

This is an ansamycin antibiotic derived from rifamycin S. Rifabutin inhibits DNA-dependent RNA polymerase, preventing chain initiation. It is used for TB treatment in individuals on specific HIV medications, when rifampin is contraindicated (most protease inhibitors).

Clofazimine (Lamprene)

Clofazimine inhibits mycobacterial growth, binding preferentially to mycobacterial DNA. It has antimicrobial properties, but its mechanism of action is unknown. It is rarely used to treat MDR-TB. Like all drugs for TB, clofazimine is always used with other antituberculous agents. Clofazimine is available only on a single-patient basis, to physicians who submit an Investigational New Drug (IND) application to the US Food and Drug Administration (FDA).

Para-aminosalicylic acid (Paser)

This is a bacteriostatic agent that is useful as a second-line agent against M tuberculosis. It is most commonly used for MDR-TB or when therapy with isoniazid or rifampin is not possible. It inhibits the onset of bacterial resistance to streptomycin and isoniazid. Administer this agent with other antituberculous drugs.

Bedaquiline (Sirturo)

Bedaquiline is a diarylquinoline that inhibits mycobacterial adenosine 5'-triphosphate (ATP) synthase, an enzyme essential for the generation of energy in Mycobacterium tuberculosis. It is indicated as part of a 22-week multidrug regimen (with at least 4 other antitubercular drugs) in adults with pulmonary MDR-TB. Therapy with bedaquiline is reserved for use when an effective treatment regimen cannot otherwise be provided. It is not indicated to treat latent, extrapulmonary, or drug-sensitive tuberculosis.

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