TB- Okamoto

• • 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

• • 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

• • Slowly progressive decline in organ function
• → Has left the lung and has infected other parts of the body

• • 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

• • 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

• • 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

• • 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

• • 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)

• • 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

• • Any person, including persons with no known risk factors for TB
• • However, targeted skin testing programs should only be conducted among high-risk groups

• • 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

• • 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

• 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

• • Drug-susceptibility results of the presumed source case (if known)
• • Coexisting medical illness
• • Drug-drug interactions
• • Adverse Effects
• • Adherence

• • Isoniazid (INH)
• • Rifampin
• • Rifapentine
• • Rifabutin*Not FDA-approved for TB
• • Ethambutol
• • Pyrazinamide

• • Cycloserine
• • Ethionamide
• • Levofloxacin
• • Moxifloxacin
• • Gatifloxacin
• • p-aminosalicylic acid
• • Streptomycin
• • Amikacin/kanamycin
• • Capreomycin

• • 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

• • Aminotransferase elevation
• • Clinical or fatal hepatitis
• → Hepatotoxicity
• • Peripheral neurotoxicity
• • CNS effects
• • Lupus-like syndrome
• • Hypersensitivity reactions
• • Diarrhea

• • Routine monitoring not necessary
• • LFTs should be measured monthly for those with abnormal liver function

• • 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

• • 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

• • No routine monitoring required
• • Evaluate for potential drug interactions

• • 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

• • Hematologic toxicity
• • Uveitis
• • GI symptoms
• • Polyarthralgia
• • Hepatotoxicity
• • Pseudojaundice
• • Rash
• • Flu-like syndrome
• • Orange discoloration of bodily fluids

• • Similar to that of rifampin
• → No predisposition for DIs like rifampin

• • 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

• • Similar to those of rifampin
• • Inducer of hepatic enzymes
• → Not to same extent as Rifampin

• • Similar to that of rifampin
• → Not to same extent as Rifampin

• • 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

• • Hepatotoxicity
• • GI symptoms
• • Polyarthralgia
• • Hyperuricemia
• • Gouty arthritis
• • Photosensitive dermatitis

• LFTs should be performed in patients with underlying liver disease, or when used with rifampin

• • First-line agent included to primarily prevent emergence of RIF resistance when primary resistance to INH may be present
• • Tablet
• • 1,200 mg Daily

• • Retrobulbar neuritis
• • Peripheral neuritis

• • Baseline visual acuity testing (monthly)
• • Testing of color discrimination (monthly)

• • 1st line does not work due to resistance
• • Toxicity
• • ADRs
• • Drug interactions

• • Slow growing organism
• • Long duration of therapy

• • Used for treating patients with drug-resistant TB caused by organisms with known/presumed susceptibility to the drug
• • Capsule

CNS effects

Neuropsychiatric status should be assessed monthly

• • Used for treating patients with drug-resistant TB caused by organisms with known/presumed susceptibility to the drug
• • Tablet

• • GI effects
• • Hepatotoxicity
• • Neurotoxicity
• • Endocrine effects

LFTs baseline and monthly in patients with liver disease

• • 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

• • Ototoxicity
• • Neurotoxicity
• • Nephrotoxicity

• • Audiogram, vestibular testing and SCr performed at baseline
• • Monthly SCr and questioning of auditory/vestibular symptoms (balance)

• • 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

• • Ototoxicity
• • Nephrotoxicity

Nephrotoxicity

• • Used for treating patients with drug-resistant TB caused by organisms with known/presumed susceptibility to the drug
• • IV/IM

• • Ototoxicity
• • Nephrotoxicity

Nephrotoxicity

• • Used for treating patients with drug-resistant TB caused by organisms with known/presumed susceptibility to the drug
• • Granules, tablets, IV/IM

• • Hepatotoxicity
• • GI distress
• • Malabsorption syndrome (decreased folate and steatorrhea)
• → Folate- megaloblastic anemia (RBC does not split)
• → Steatorrhea- inability to secrete pancreatic lipases
• • Hypothyroidism
• • Coagulopathy

• • LFTs
• • Thyroid function tests

• • 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

• • GI distress
• • Neurologic
• • Cutaneous

No routine monitoring

• First novel TB drug in over 40 years
• • Accelerated approval 12/2012
• • 24 weeks of therapy

• • Treatment of MDR pulmonary TB
• • Use with ≥3 active TB drugs
• • Only use if no other effective treatment regimen is available

• • Increased risk of death in clinical trials of bedaquiline versus placebo
• • Risk of QT prolongation

• • Substitute rifabutin in place of rifampin
• • Highly intermittent regimens not recommended

• • 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)

• • Isoniazid, rifampin, and ethambutol for 9 months
• → Pyrazinamide not routinely recommended

• Ethambutol not routinely recommended

• Longer duration of therapy