TB- Okamoto

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  1. Latent TB Infection
    • • TB infection is contained by host’s immune system
    • → No symptoms or physical findings suggestive of TB disease
    • → Retains potential to develop into active disease
    • → Positive reaction to tuberculin skin test (TST) or TB blood test (Interferon Gamma Release Assay (IGRA))
    • • Not infectious
    • • Chest radiograph is typically normal
    • • If done, respiratory specimens are smear and culture negative
    • → Replicating intracellularly
    • • Should consider treatment for LTBI to prevent TB disease
  2. Active TB (Pulmonary) Infection
    • • Gradual onset
    • → Slow growing organism- can take weeks to months to years
    • • Symptomatic, actively replicating (≥ 1 of following)
    • → Fever, productive cough, chest pain, weight loss, night sweats, hemoptysis (sign of advanced TB), fatigue, and decreased appetite
    • • Infectious
    • • TST/IGRA result usually positive
    • • Atypical presentations may occur in HIV-positive patients and/or elderly patients
    • • Chest radiograph is usually abnormal (i.e. infiltrates and cavitary lesions)
    • → However, may be normal in persons with advanced immunosuppression or extrapulmonary disease
    • • Respiratory specimens are usually smear or culture positive
    • → However, may be negative in persons with extrapulmonary disease or minimal or early pulmonary disease
    • • Needs treatment for TB disease
  3. Active TB (Extra-pulmonary) Infection
    • • Slowly progressive decline in organ function
    • → Has left the lung and has infected other parts of the body
  4. Clinical Manifestations: Primary Infection
    • • Inflammatory response may lead to tissue necrosis and calcification of infected site
    • → Caseous necrosis- calcification
    • • 90% will have no clinical manifestations
    • • 5% may have progressive primary disease
  5. Clinical Manifestations: Secondary Infection (Reactivation)
    • • Organisms within granulomas emerge and begin multiplying extracellularly leading to inflammation and tissue necrosis
    • → Aveoli destroyed
    • • Pulmonary
    • → Coughing, hemoptysis
    • • Extrapulmonary
    • → Dissemination- infection leaving the lungs
    • • Miliary
    • → All throughout the body- all organs infected
  6. Risk Factors for TB Infection
    • • Place of birth
    • → Mexico, Philippines, Vietnam, India, China
    • • Location
    • → California, Florida, New York, Texas (highly populated & large number of immigrants)
    • → Urban areas
    • • Close contacts
    • → Family, coworkers, residents in prisons/shelters/nursing homes
    • • Age (25 to 64 years)
    • • Ethnic minorities (socioeconomic factors)
    • → Hispanic, African American, Asian
    • • Other
    • → Limited access to healthcare
    • → Homeless
    • → Alcohol and/or drug abuse
    • → Coinfection: HIV/AIDS, Hepatitis B
  7. Purified Protein Derivative (PPD) skin test
    • • Becomes positive about 1 to 3 months after infection
    • → Cannot screen newly infected patients
    • • 0.1 mL of 5-tuburculin-unit PPD dose placed intradermally
    • • T-cells in sensitized individuals lead to an inflammatory response causing induration (raised area)
    • • Induration diameter read in 48 to 72 hours (need to measure size)
    • • Interpretation also depends on TB infection risk and risk of progression to active disease
    • • False positives occur in patients who received the Bacillius Calmette Guerin (BCG) Vaccine
    • → BCG Vaccine often given in countries with high degree of tuberculosis disease
    • • False negatives occur in up to 20% patients
    • → No reaction on skin when they actually have the disease
  8. Induration ≥ 5 mm + Risk Factors
    • • HIV-infected persons
    • • Recent contact of a person with TB disease
    • • Persons with fibrotic changes on chest radiograph consistent with prior TB
    • • Patients with organ transplants
    • • Persons who are immunosuppressed for other reasons (e.g., taking the equivalent of >15 mg/day of prednisone for 1 month or longer, taking TNF-α antagonists)
  9. Induration ≥ 10 mm + Risk Factors
    • • Recent immigrants (< 5 years) from high-prevalence countries
    • • Parenteral drug users (IVDU)
    • • Residents & employees of high-risk congregate settings
    • • Mycobacteriology laboratory personnel
    • • Persons with clinical conditions that place them at high risk
    • • Children < 4 years old
    • • Infants, children, & adolescents exposed to adults in high-risk categories
  10. Induration ≥ 15 mm + Risk Factors
    • • Any person, including persons with no known risk factors for TB
    • • However, targeted skin testing programs should only be conducted among high-risk groups
  11. Blood Test (Interferon-gamma Release Assays or IGRAs)
    • • Preferred in people who have:
    • → Received bacille Calmette-Guérin (BCG) vaccine
    • → Pts that cannot return for a second appointment to look for a reaction to the skin test
  12. Other TD Dx
    • • AFB sputum smears
    • → Daily morning sputum over 3 consecutive days
    • • Culture (6 weeks)
    • → Slow growing, takes a while
    • • Chest X-Ray
    • • Other:
    • → Elevated WBC count
    • → Signs and symptoms
  13. Steps in TB Disease
    • Clinical evaluation for active TB and start therapy
    • • Chest X-Ray, AFB sputum smear x 3, sputum culture, HIV test
    • • Multi-drug regimen for 6-9 months

    • Isolation
    • • Negative pressure rooms in hospital
    • → Specific requirements for controlled ventilation, negative pressure, and air filtration
    • • Home on isolation

    • Report to state’s Department of Health
    • • Assigned a case number; track patient’s location and DOT (directly observed therapy)
    • → Most effective strategy for making sure patients take medications
    • • Monitor
    • → Adherence
    • → Adverse Effects
    • → Drug Interactions
    • → AFB sputum smears every 1 to 2 weeks until two consecutive smears are negative
    • • All places and persons whom patient has been in contact
  14. Factors to Consider When Starting Therapy
    • • Drug-susceptibility results of the presumed source case (if known)
    • • Coexisting medical illness
    • • Drug-drug interactions
    • • Adverse Effects
    • • Adherence
  15. First line drugs for TB
    • • Isoniazid (INH)
    • • Rifampin
    • • Rifapentine
    • • Rifabutin*Not FDA-approved for TB
    • • Ethambutol
    • • Pyrazinamide
  16. Second line drugs for TB
    • • Cycloserine
    • • Ethionamide
    • • Levofloxacin
    • • Moxifloxacin
    • • Gatifloxacin
    • • p-aminosalicylic acid
    • • Streptomycin
    • • Amikacin/kanamycin
    • • Capreomycin
  17. Isoniazid (INH)
    • • AKA: Iso Nicotinyl Hydrazide
    • • First line agent for all forms of TB caused by organisms known or presumed to be susceptible
    • • Profound bactericidal activity against rapidly dividing cells (active TB)
    • • Tablets, elixer, IV/IM
    • • 300 mg Daily 6-9 months
  18. Isoniazid (INH) ADRs
    • • Aminotransferase elevation
    • • Clinical or fatal hepatitis
    • → Hepatotoxicity
    • • Peripheral neurotoxicity
    • • CNS effects
    • • Lupus-like syndrome
    • • Hypersensitivity reactions
    • • Diarrhea
  19. Isoniazid (INH) Monitoring
    • • Routine monitoring not necessary
    • • LFTs should be measured monthly for those with abnormal liver function
  20. Rifampin (RIF)
    • • First line agent for all forms of TB caused by organisms known or presumed to be susceptible
    • • Has activity against organisms that are dividing rapidly (active TB)
    • • Has activity against semi-dormant bacterial populations (latent infections)
    • • Is an essential component of all short-course regimens
    • • Capsule, powder/suspension, IV
    • • 600 mg
  21. Rifampin (RIF) ADR
    • • Cutaneous reactions
    • • GI reactions
    • • Flu-like syndrome
    • • Hepatotoxicity
    • • Severe immunologic reactions
    • • Orange discoloration of bodily fluids
    • Induction of hepatic enzymes / drug interactions
    • → Drugs will be metabolized at a faster rate
  22. Rifampin (RIF) Monitoring
    • • No routine monitoring required
    • • Evaluate for potential drug interactions
  23. Rifabutin
    • • Used as a substitute for rifampin for all forms of TB caused by organisms known or presumed to be susceptible
    • • Commonly used for patients that are having unacceptable drug interactions with rifampin or are intolerant to rifampin
    • • Capsule
  24. Rifabutin ADRs
    • • Hematologic toxicity
    • • Uveitis
    • • GI symptoms
    • • Polyarthralgia
    • • Hepatotoxicity
    • • Pseudojaundice
    • • Rash
    • • Flu-like syndrome
    • • Orange discoloration of bodily fluids
  25. Rifabutin Monitoring
    • • Similar to that of rifampin
    • → No predisposition for DIs like rifampin
  26. Rifapentine
    • • May be used once weekly with INH in the continuation phase of treatment for HIV seronegative patients with non-cavitary, drug susceptible pulmonary TB with negative sputum smears at completion of the initial phase of Tx
    • • Tablet
  27. Rifapentine ADRs
    • • Similar to those of rifampin
    • • Inducer of hepatic enzymes
    • → Not to same extent as Rifampin
  28. Rifapentine Monitoring
    • • Similar to that of rifampin
    • → Not to same extent as Rifampin
  29. Pyrazinamide (PZA)
    • • First line agent for all forms of TB caused by organisms known or presumed to be susceptible to the drug
    • • Believed to exert greatest activity against population of dormant or semidormant organisms contained within macrophages or the acidic environment of caseous foci (necrotic pockets)
    • • Tablet
    • • 1,500 mg Daily
  30. Pyrazinamide (PZA) ADRs
    • • Hepatotoxicity
    • • GI symptoms
    • • Polyarthralgia
    • • Hyperuricemia
    • • Gouty arthritis
    • • Photosensitive dermatitis
  31. Pyrazinamide (PZA) Monitoring
    • LFTs should be performed in patients with underlying liver disease, or when used with rifampin
  32. Ethambutol (EMB)
    • • First-line agent included to primarily prevent emergence of RIF resistance when primary resistance to INH may be present
    • • Tablet
    • • 1,200 mg Daily
  33. Ethambutol (EMB) ADRs
    • • Retrobulbar neuritis
    • • Peripheral neuritis
  34. Ethambutol (EMB) Monitoring
    • • Baseline visual acuity testing (monthly)
    • • Testing of color discrimination (monthly)
  35. Use of Second Line Drugs
    • • 1st line does not work due to resistance
    • • Toxicity
    • • ADRs
    • • Drug interactions
  36. Reasons for Resistance (MDR)
    • • Slow growing organism
    • • Long duration of therapy
  37. Cycloserine
    • • Used for treating patients with drug-resistant TB caused by organisms with known/presumed susceptibility to the drug
    • • Capsule
  38. Cycloserine ADRs
    CNS effects
  39. Cycloserine Monitoring
    Neuropsychiatric status should be assessed monthly
  40. Ethionamide
    • • Used for treating patients with drug-resistant TB caused by organisms with known/presumed susceptibility to the drug
    • • Tablet
  41. Ethionamide ADRs
    • • GI effects
    • • Hepatotoxicity
    • • Neurotoxicity
    • • Endocrine effects
  42. Ethionamide Monitoring
    LFTs baseline and monthly in patients with liver disease
  43. Streptomycin (SM)
    • • Approximately equal to EMB in initial phase of treatment with 6 month regimens.
    • • May have relatively high rate of resistance when TB is acquired in high-incidence countries
    • • IV/IM
  44. Streptomycin (SM) ADRs
    • • Ototoxicity
    • • Neurotoxicity
    • • Nephrotoxicity
  45. Streptomycin (SM) Monitoring
    • • Audiogram, vestibular testing and SCr performed at baseline
    • Monthly SCr and questioning of auditory/vestibular symptoms (balance)
  46. Amikacin & kanamycin
    • • Used for treating patients with drug-resistant TB caused by organisms with known/presumed susceptibility to the drug
    • • Frequent cross-resistance to these drugs
    • • Most SM-resistant strains are susceptible to these aminoglycosides
    • • IV/IM
  47. Amikacin & kanamycin ADRs
    • • Ototoxicity
    • • Nephrotoxicity
  48. Amikacin & kanamycin Monitoring
    Nephrotoxicity
  49. Capreomycin
    • • Used for treating patients with drug-resistant TB caused by organisms with known/presumed susceptibility to the drug
    • • IV/IM
  50. Capreomycin ADRs
    • • Ototoxicity
    • • Nephrotoxicity
  51. Capreomycin Monitoring
    Nephrotoxicity
  52. p-aminosalicylic acid
    • • Used for treating patients with drug-resistant TB caused by organisms with known/presumed susceptibility to the drug
    • • Granules, tablets, IV/IM
  53. p-aminosalicylic acid ADRs
    • • Hepatotoxicity
    • • GI distress
    • • Malabsorption syndrome (decreased folate and steatorrhea)
    • → Folate- megaloblastic anemia (RBC does not split)
    • → Steatorrhea- inability to secrete pancreatic lipases
    • • Hypothyroidism
    • • Coagulopathy
  54. p-aminosalicylic acid Monitoring
    • • LFTs
    • • Thyroid function tests
  55. Levofloxacin, Moxifloxacin, Gatifloxacin
    • • Levofloxacin is preferred oral agent for treating drug-resistant TB in susceptible patients or when first-line agents can’t be used because of intolerance
    • • Tablets, IV
  56. Levofloxacin, Moxifloxacin, Gatifloxacin ADRs
    • • GI distress
    • • Neurologic
    • • Cutaneous
  57. Levofloxacin, Moxifloxacin, Gatifloxacin Monitoring
    No routine monitoring
  58. Bedaquiline (Sirturo®)
    • First novel TB drug in over 40 years
    • • Accelerated approval 12/2012
    • • 24 weeks of therapy
  59. Bedaquiline (Sirturo®) Indication
    • • Treatment of MDR pulmonary TB
    • • Use with ≥3 active TB drugs
    • • Only use if no other effective treatment regimen is available
  60. Bedaquiline (Sirturo®) ADR (Black Box Warning)
    • • Increased risk of death in clinical trials of bedaquiline versus placebo
    • • Risk of QT prolongation
  61. HIV/AIDS in TB
    • • Substitute rifabutin in place of rifampin
    • • Highly intermittent regimens not recommended
  62. Hepatic Failure in TB
    • • Suspect hepatotoxicity in patients with the following
    • → Transaminases > 5 x ULN or Total bilirubin > 3
    • → Nausea, vomiting, jaundice
    • • Sequential reintroduction with frequent testing of liver enzymes to identify the offending agent
    • • Alternative agents selected as needed
    • → “liver sparing regimen” – streptomycin, levofloxacin, ethambutol
    • ¤ Requires minimum of 18 months duration (longer duration of Tx)
  63. Pregnancy in TB
    • • Isoniazid, rifampin, and ethambutol for 9 months
    • → Pyrazinamide not routinely recommended
  64. Pediatrics in TB
    • Ethambutol not routinely recommended
  65. Extra-pulmonary TB
    • Longer duration of therapy

Card Set Information

Author:
ebmalonzo
ID:
316083
Filename:
TB- Okamoto
Updated:
2016-02-21 15:05:07
Tags:
TB
Folders:
ID 1
Description:
ID 1 (Final): TB (Okamoto)
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