Tuberculosis treatment

Tuberculosis is an infection-borne disease caused by Mycobacteria. This illness requires long-term combined treatment in order to cure the disease, avoid the destruction of the lungs, prevent relapses in the future and morbidity. Untreated tuberculosis is often lethal, but with the help of modern chemotherapeutic agents, it can be treated effectively.  

Principles of therapy

  • Intravenous infusionThe main aims of the tuberculosis treatment is to interrupt the infection transmission by cessation of bacteria liberation and thereby protect person’s family and maintain public health, relieve the symptoms of the disease, prevent the death of a seriously ill person, prevent the development of drug resistance, avoid the diffuse lungs involvement and fibrotic changes, and prevent future recurrence of tuberculosis;
  • A person should be treated with a combination of bactericidal drugs (drugs that kill the bacteria and effectively reduce the number of Mycobacteria) administered for at least 6 months despite the possible side effects. Combined therapy is much more effective because Mycobacteria may be resistant to some medications, but usually cannot survive combined regimens;
  • The drug susceptibility test (DST) is recommended before the treatment initiation in order to verify whether the bacteria is resistant to any medications or not. The treatment regimens should be chosen according to the results of the DST;
  • Typically, first-line drugs are used for the treatment of tuberculosis. However, when resistance to any of these first-line drugs is found or suspected, or when a person develops side effects of first-line drugs during therapy, the treatment should include second-line drugs;
  • In case of active tuberculosis sputum analysis for Mycobacterium tuberculosis should be performed regularly until Mycobacteria are no longer detected;
  • A high level of treatment adherence is required to provide appropriate therapy results, prevent tuberculosis relapse and the development of drug resistance. Therefore, medical workers are supposed to control whether a person consumes the medications or not vie direct supervision;

First-line drugs

  • Isoniazid remains one of the most significant drugs used for the tuberculosis treatment and it should be included in every regimen unless the strain is resistant to this drug. It has a potent antibacterial activity and within a few days, infectiousness and the sputum bacterial load decrease drastically. Isoniazid is toxic to the liver and rarely may cause hepatitis and jaundice. Other known side effects of isoniazid are peripheral neuritis characterized by the burning sensations in the feet and allergic reactions manifesting with itching and skin rash. The administration of vitamin B6 (pyridoxine at a dose of 10-25 mg/day) helps to reduce the risk of developing peripheral neuropathy.
  • Rifampin acts on slowly multiplying bacteria, and therefore, especially effectively reduces the risk of recurrence after the regimen is completed. Thus the duration of therapy may be shortened to 9 and fewer months. Without rifampin, the recommended treatment duration should be more than 18 months. During the administration of rifampin body fluids such as urine, tears, sweat, and sputum as well as contact lenses and dentures gain orange-red color.
  • The addition of pyrazinamide permits to shorten treatment duration up to 6 months. Pyrazinamide is associated with joint pain (arthralgias which can be relieved by nonsteroidal anti-inflammatory drugs) and severe liver damage.
  • Ethambutol is able to prevent the development of resistance to isoniazid. Optic neuritis as a side effect of treatment with ethambutol occurs rarely in persons with impaired renal function.
  • Streptomycin for decades was used as a first-line drug for the treatment of tuberculosis, although lately it is not prescribed so often anymore due to the high level of resistance to it and drug toxicity.

Second-line drugs

  • Capreomycin has bacteriostatic properties. The drug affects the frequency of urination or the amount of urine, increases thirst and may cause loss of appetite, nausea, and vomiting.
  • Aminoglycosides (kanamycin, amikacin) may affect a person’s auditory system and cause renal impairment.
  • Thioamides (ethionamide and prothionamide) are known to produce gastrointestinal disorders (such as anorexia, excessive salivation, nausea, vomiting, metallic taste, abdominal pain, and diarrhea), various mental disturbances (such as depression, anxiety, psychosis, dizziness, drowsiness, and headache) and hypersensitivity skin reactions.
  • Fluoroquinolones (levofloxacin, gatifloxacin, moxifloxacin) in general are well-tolerated and cause limited side effects.
  • Cycloserine is a highly-toxic medication that may produce various adverse reactions affecting the central nervous system.
  • PAS (para-aminosalicylic acid) is a relatively cheap drug that is used in low-resource countries despite its side effects.
  • Thiacetazone produces diverse adverse reactions including nausea, vomiting, skin rashes, conjunctivitis, vertigo, and jaundice. Individuals with liver impairment and HIV shouldn’t receive it due to the increased risk of side effects.

Treatment regimens

The treatment regimen is usually comprised of the initial phase when 3 or more drugs are administered for 2 months in order to stop the bacteria replication and as the result reduce the presence of bacteria in the sputum. Afterward, the treatment continues with the administration of fewer drugs (usually isoniazid and rifampicin) for 4 to 7 months depending on the activity of the disease.

The standard treatment regimen includes a 2-month initial phase during which isoniazid, rifampin, pyrazinamide, and ethambutol are given, followed by a 4-month continuation therapy with isoniazid and rifampin. When Mycobacteria are still observed in the sputum (the sputum is culture-positive) the continuation therapy should be extended by 3 months with a total treatment course of at least 9 months. On the other hand, the treatment may be reduced to 4 months if there are no bacteria in the sputum (the sputum is culture-negative).

Drugs may be given daily or intermittently – three or two times a week, although the administration of the drugs twice a week is considered less effective.

Persons with latent tuberculosis should receive chemoprophylaxis by the administration of isoniazid only at doses of 300 mg daily for 6 to 9 months.

Precautions

Streptomycin and other aminoglycosides should not be prescribed for pregnant women as they are ototoxic for the fetus – namely, it can damage his auditory and vestibular system.

Pyrazinamide is contraindicated in case of severe liver disease. Renal failure is a contraindication to thioacetazone.

Surgical treatment

In case of multidrug-resistant tuberculosis surgical resection of the involved lung (segmentectomy, lobectomy and pneumonectomy) may be considered.

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