Tuberculosis (TB)

Tuberculosis = Mycobacterium tuberculosis
Risk factors, pathophysiology, epidemiology, and diagnostic criteria for tuberculosis

  • Risk factors for infection:  location/place of birth, traveling, immigrants, ethnicity (minorities), HIV, chemical dependency (exposure to high risk groups)
  • Risk factors for the active disease:  time since infection (increased risk if within 2 years since acquiring the infection), age (increased risk for pts under 2 or over 65), immune deficiency, HIV infection
  • Pathophysiology of the infection:  inhalation of TB droplet from a cough/sneeze by an infected person.  This droplet deposits on the upper alveolar surface of the lung & forms a solid caseous (necrotic) granuloma containing the bacteria in the lung tissue
  • Activation/Reactivation of TB:  the caseating (necrotizing) granulomas cause cavities in the lungs (lung destruction typically in the posterior (back) upper lobe) resulting in hypoxia, respiratory acidosis & potentially death
    • Note that TB can also affect other body systems & potentially become disseminated (miliary TB) especially in patients who also have HIV
      • In patients that develop pericarditis or CNS TB, use adjunctive corticosteroid therapy
    • Untreated TB is fatal in about 50% of patients w/in 5 years
  • Diagnosis:
    • Skin Testing (PPD)
      • Area of induration:  > 5 mm; > 10 mm; > 15mm (Quantitative measure; checked after 2-3 days)
        • 5mm:  HIV+, recent contact w/ ppl w/ TB, fibrotic changes in chest radiograph consistent w/ previous TB, pts who’ve received an organ transplant or are otherwise immunosuppressed
        • 10mm:  recent immigrants from a country w/ high-prevalence(w/in last 5 years), IV drug users, residents or employees of high risk settings (prison, HC facilities, lab personnel, etc), ppl w/ significant comorbidities, kids younger than 4 or kids exposed to adults that are at high risk
        • 15mm:  no risk factors
      • Positive result indicates the need for further testing & the consideration of a Rx (based on whether the TB is latent or active)
      • If you have a positive PPD test, check signs & symptoms & do a chest X-ray  (also take if sputum/fluid drainage samples if available)
        • chest X-rays show areas of opacities (light is able infiltrate) & the appearance of cavities
  • Epidemiology:  typically seen in asia, africa & brazil
    • ~2 billion ppl world wide are infected w/ TB, accounts for ~1.3 million deaths annually
    • ~13 million ppl in the US have latent TB, w/ the highest rates being in CA, FL, IL, NY, TC
      • Annual incidence has been decreasing but there is persistent new exposure/importation of TB into this country due to travelers

Latent Vs. active tuberculosis

  • Latent TB
    • No cough or other signs/symptoms  (usually will have a + PPD though)
    • can NOT spread TB to others but have an increased risk of activating the disease if their immune system becomes depressed
    • Management of latent infection:
      • Isoniazid daily x 9 months + Vitamin B 6 is the preferred regimen for latent TB
        • Any time an intermittent drug regimen is used (twice weekly), you must use DOT (directly observed therapy)
      • Young, old, HIV+ & other high risk pts who have latent TB need to get a prophylactic treatment to rule out the active disease
        • In recent converters, prophylactic therapy should also be strongly considered, but for low risk patients (chest x-ray negative) prophylaxis for latent TB is more controversial
Latent TB Treatment Regimens

 

Regimen

Schedule

Isoniazid

(INH)

Daily for 9 months (preferred treatment)

 

Twice weekly for 9 months (Patients should receive directly observed therapy–DOT)

 

Daily for 6 months (Patients should receive directly observed therapy–DOT. Not recommended in patients w/ HIV, previous TB, or in children)

 

Twice weekly for 6 months (Not recommended in patients w/ HIV, previous TB, or in children)

Rifampin (RIF)

Daily for 4 months (alternative for patients who can’t tolerate or are resistant to isoniazid—INH)

  • Active TB
    • Ppl less than 2 or older than 65 or who are immunosuppressed (ex. HIV, cancer, steroids, mab’s) are most likely to develop the active disease
    • Clinical presentation of active TB:  productive cough/chest pain lasting over 2 weeks, progressing pulmonary symptoms, night sweats/chills/fever, hemoptysis (coughing up blood), may or may not have an abnormal chest X-ray
      • HIV patients often have atypical symptoms
      • Elderly patients may have muted or no symptoms at all
      • Children (< 12) usually have rapidly progressing symptoms
    • Standard therapy of active disease (HIV-/HIV+)
      • Requires respiratory isolation & multiple drugs
        • INH/Rifampin is a primary trxt option  (may need to extend duration of therapy in pts w/ HIV or immunosuppression)
          • Avoid intermittent regimens w/ HIV + pts, also be aware of the possibility of malabsorption & DDIs w/ these pts
      • If the patient requires retreatment, expect that resistance has developed
      • INITIAL PHASE:  INH (isoniazid) + RIF (rifampin) + PZA (pyrazinamide) + EMB (ethambutol)
        • This therapy should be either be for
          • 7 days a week for 8 weeks
          • Or 5 days a week for 8 weeks (directly observed therapy–DOT)
      • CONTINUATION PHASE:  INH (isoniazide) + RIF (rifampin)
        • This therapy should be done as follows:
          • Either 7 days a week for 18 weeks
          • Or 5 days a week for 18 weeks (directly observed therapy–DOT)
            • The two above treatments are preferred but the combo could also be done twice weekly for 18 weeks under DOT
      • Altogether active TB therapy should last 26 weeks & a smear & culture should be done after 2 months of therapy

Drug alternatives for MDR-TB patients

  • (MDR-TB:  pt is resistant to INH & RIF)
  • Quinolones (levo, moxi & gatifloxacin)
  • Aminoglycosides (streptomycin, kanamycin, amikacin, capreomycin)
    • Capreomycin & streptomycin don’t have any cross resistance w/ the other aminoglycosides
  • Cycloserine
  • Clofazimine

Reasons to suspect drug resistance during TB therapy:

  • Prior TB therapy
  • Patient from geographical area with high prevalence of resistance
  • Homeless/institutionalized/IV drug abusers/HIV
  • Known exposure to MDR-TB index case
  • Drug failure/relapse
    • If post 1-2 months after drug:  AFB & (+)sputum smears
    • If post 2-4 months after drug:  Positive culture
  • Specialist consult/referral imperative

Management issues related to use of:

  • Isoniazid; Rifampin, Pyrazinamide, and Ethambutol
    • Isoniazid:  300 mg/day for adults & dosed by weight for pediatrics
      • Fast acetylators (Asians/Eskimos mainly–80-90%, but also whites & blacks) will have poor outcomes w/ intermittent treatment regimens (watch out for Crohn’s disease as well)
      • Slow acetylators have an increased risk of neurotoxicity & hepatotoxicity
        • Vitamin B6 (pyridoxine will decrease neurotoxicity)
      • Increases in liver function tests are common especially in the first 8-12 weeks (watch out for hepatotoxicity)
      • Take ING on an empty stomach ideally or w/ a small meal
    • Rifampin (potent inducer of 3A4):
      • Daily dosing is best (SE are actually lower w/ daily dosing than intermittent dosing, better efficacy, decreased resistance)
      • Absorption is decreased in pts w/ AIDS, DM, GI diseases
      • Drug resistance is a major concern with RIF
      • Decreases oral contraceptive efficacy
      • Colors bodily secretions (urine/tears/other) orange-red
    • Ethambutol (EMB)
      • Decrease this dose in pts w/ renal failure
      • Don’t give w/ antacids
      • May adversely affect eyes’ acuity & ability to discriminate colors
    • Pyrazinamide (PZA)
      • AE:  hepatotoxicity, HI, arthralgias, increase in uric acid
  • Goals/critical components of DOT (directly observed therapy)
    • Communicate the importance of adherence (pt may take INH w/ a small amount of food if it isn’t tolerated well on an empty stomach)
  • Rifamate = INH 150 mg + RIF 300 mg.  Tk 2 cs po qd
  • Rifater = INH 50 mg + RIF 120 mg + PZA 300 mg.  Tk 5-6 ts po qd
  • In children use higher doses of INH/RIF (based on mg/kg vs. adult dosing) & use for longer (9 months)
  • Pregos w/ active TB should get INH/RIF/EMB for 9 months + vitamin B6 (pyridoxine).
    • If it’s a latent infection probably wait til after birth to admin meds
  • Morbidly obese patients should be dosed on IBW
  • The WHO recommends that the BCG (TB vaccine) be given to infants & young children in countries where TB is common
    • Not recommended in the US

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