TB

• Tuberculosis (TB) is a communicable infectious disease caused by Mycobacterium tuberculosis
• TB can produce silent, latent infection, as well as progressive, active disease
• In 2019, there were about 10 million new cases and 1.2 million deaths from TB reported
• Transmission of M. tuberculosis

  1. Coughing or other activities that cause the organism to be aerosolized

  2. Close contacts of TB patients are most likely to become infected
• Human immunodeficiency virus (HIV)

  The most important risk factor for progressing to active TB
• An HIV-infected individual with TB infection is over 100-fold more likely to develop active disease than an HIV-seronegative patient
• Miliary TB

  Widely disseminated disease and granuloma formation caused by a massive inoculum of organisms introduced into the bloodstream
• Types of tuberculosis

  • Latent infection
  • Cavitary tuberculosis
  • Miliary tuberculosis
• Patients with TB

  • Typically present with cough, weight loss, fatigue, fever, and night sweats
  • Symptom onset may be gradual
  • Frank hemoptysis usually occurs late in the course of disease but may present earlier
• Diagnosis of TB

  1. Sputum smear to detect mycobacteria

  2. Chest radiograph

  3. Clinical features associated with extrapulmonary TB vary depending on the organ system(s) involved
• Patients with HIV and TB

  • May have atypical presentation
  • Less likely to have positive skin tests, or fever
  • Higher incidence of extrapulmonary TB
  • More likely to present with progressive primary disease
• Tuberculin skin test

  The most widely used screening method for tuberculous infection, using purified protein derivative (PPD)
• Confirming active TB

  1. Attempts should be made to isolate M. tuberculosis from the infected site

  2. Daily sputum collection over 3 consecutive days is recommended

  3. Tests to measure release of interferon-y in the patient's blood in response to TB antigens may provide quick and specific results for identifying M. tuberculosis
• Goals of TB treatment

  • Rapid identification of a new TB case
  • Initiation of specific anti-TB treatment
  • Eradicating M. tuberculosis infection
  • Achievement of a noninfectious state in the patient, thus ending isolation
  • Preventing the development of resistance
  • Adherence to the treatment regimen by the patient
  • Cure of the patient as quickly as possible (generally at least 6 months of treatment)
• Patients with active disease should be isolated to prevent spread of the disease
• Drug treatment

  • The cornerstone of TB management
  • A minimum of two drugs, and generally three or four drugs, must be used simultaneously
• Directly observed therapy (DOT)

  A cost-effective way to ensure completion of treatment and is considered the standard of care
• Drug treatment is continued for at least 6 months, and 18-24 months for cases of multidrug-resistant TB (MDR-TB)
• Surgery may be needed to remove destroyed lung tissue, space-occupying lesions, and some extrapulmonary lesions
• Chemoprophylaxis


  Should be initiated in patients to reduce the risk of progression to active disease
• Recommended treatment regimens for latent tuberculosis infection (LTBI)

  • 3 months of once weekly isoniazid plus rifapentine
  • 4 months of daily rifampin
  • 3 months of daily isoniazid plus rifampin
• 12-week isoniazid/rifapentine regimen

  Recommended by the Centers for Disease Control and Prevention (CDC) as an equal alternative to 9 months of daily isoniazid for treating LTBI in otherwise healthy patients aged 12 years or older who have greater likelihood of developing active TB
• Pregnant women, alcoholics, and patients with poor diets who are treated with isoniazid should receive pyridoxine, 10-50 mg daily, to reduce the incidence of central nervous system (CNS) effects or peripheral neuropathies
• Drugs for treating latent tuberculosis infection

  • Isoniazid
  • Rifapentine
  • Rifampin
• Vitamins for treating latent tuberculosis infection

  • Pyridoxine (Vitamin B6)
• Drug regimens for microbiologically confirmed pulmonary tuberculosis caused by drug susceptible organisms

  • Regimen 1: Isoniazid, Rifampin, Pyrazinamide, Ethambutol
  • Regimen 2: Isoniazid, Rifampin, Pyrazinamide, Ethambutol
• Standard TB treatment regimen

  Isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months, followed by isoniazid and rifampin for 4 months (a total of 6 months of treatment)
• Ethambutol can be stopped if susceptibility to isoniazid, rifampin, and pyrazinamide is shown
• Evaluating a patient for retreatment of TB

  It is imperative to know what drugs were used previously and for how long
• Drugs for treating active pulmonary tuberculosis

  • Isoniazid
  • Rifampin
  • Pyrazinamide
  • Ethambutol
• If the organism is drug resistant, the aim is to introduce two or more active agents that the patient has not received previously
• With MDR-TB, no standard regimen can be proposed
• It is critical to avoid monotherapy or adding only a single drug to a failing regimen
• Situations where drug resistance should be suspected

  • Patients who have received prior therapy for TB
  • Patients from geographic areas with a high prevalence of resistance
  • Patients who are homeless, institutionalized, IV drug abusers, and/or infected with HIV
  • Patients who still have acid-fast bacilli-positive sputum smears after 2 months of therapy
  • Patients who still have positive cultures after 2-4 months of therapy
  • Patients who fail therapy or relapse after retreatment
  • Patients known to be exposed to MDR-TB cases
• Tuberculous meningitis and extrapulmonary disease

  • Isoniazid, pyrazinamide, ethionamide, cycloserine and linezolid penetrate the cerebrospinal fluid readily
  • Patients with CNS TB are often treated for longer periods (9–12 months)
  • Extrapulmonary TB of the soft tissues can be treated with conventional regimens
  • TB of the bone is typically treated for 9 months, occasionally with surgical debridement
• TB treatment in children

  • May be treated with regimens similar to those used in adults, although some physicians still prefer to extend treatment to 9 months
  • Pediatric doses of drugs should be used
• TB treatment in pregnant women

  • Isoniazid, rifampin, and ethambutol for 9 months
  • Isoniazid or ethambutol is relatively safe when used during pregnancy
  • Rifampin has been rarely associated with birth defects, but those seen are occasionally severe
  • Pyrazinamide has not been studied in a large number of pregnant women, but anecdotal information suggests that it may be safe
  • Ethionamide may be associated with premature delivery, congenital deformities, and Down syndrome when used during pregnancy, so it cannot be recommended in pregnancy
  • Cycloserine is not recommended during pregnancy
  • Fluoroquinolones should be avoided in pregnancy and during nursing
• TB treatment in renal failure

  • Isoniazid and rifampin do not require dose modifications
  • Pyrazinamide and ethambutol typically require a reduction in dosing frequency from daily to three times weekly
• Ensuring adherence to TB therapy

  • The most serious problem is nonadherence to the prescribed regimen
  • The most effective way to ensure adherence is with DOT
• Monitoring for toxicity during TB treatment

  1. Patients should have blood urea nitrogen, serum creatinine, aspartate transaminase or alanine transaminase, and a complete blood count determined at baseline and periodically

  2. Hepatotoxicity should be suspected in patients whose transaminases exceed five times the upper limit of normal or whose total bilirubin exceeds 3 mg/dL

  3. At this point, the offending agent(s) should be discontinued and alternatives selected