Tuberculosis

TB is the leading killer of people with ___

HIV

Do more people have active or latent TB?

latent

Where are 50% of new TB cases found?

california, texas, new york, florida, illinois

In what part of the state are you likely to see a large number of TB cases?

big city areas

What organism is TB caused by?

Mycobacterium tuberculosis

Characteristics of Mycobacterium tuberculosis

• aerobic bacili with a thick, waxy, cell wall

• very slow growing

• generation time >15 hours

Why is it an issue that TB has a slow generation time?

it slows down our ability to identify effective treatment management or the presence of bacteria

risk factors for TB

• foreign travel/residence

• close contact with infected person

• immune weakness (diabetes, HIV, excess alcohol use)

• IV drug use (sharing needles)

How is TB spread?

droplet nuclei (airborne)

Inoculum

enough of the organism to overwhelm your immune system and have the organism establish residence in your body

What are the different ways to reach the inoculum?

• duration of exposure

• frequency of exposure

• proximity to infected person

3 types of TB

• latent TB

• active pulmonary TB

• extra-pulmonary TB

Risk of reactivation with latent TB

• non-HIV coinfection: 5% in the first 2 years and 5% thereafter

• HIV coinfection- 5-10% per year

Someone with latent TB will test positive for what

TB skin test/IGRA

greatest risk of reactivation for TB

• HIV coinfection

• contact with an infected person

• use of corticosteroids

• chronic kidney disease

• smokers

• diabetes

(anything that dampens immune system)

active pulmonary TB is when what happens?

tubercule bacilli reach the alveoli of the lungs

How is active pulmonary TB spread?

blood

Symptoms of active TB disease

• fever

• weight loss

• night sweats

• productive cough

• hemoptysis

• fatigue

Extra-pulmonary TB/military is when TB is found where?

• lymph node

• pleural

• bone and joint

• central nervous system

(more than one place)

TB skin test

• .0001 mf of PPD

• induration read 48-72 hrs after injection (they have to come back)

• false positives and negatives common

• positive in patients receiving BCG vaccine (false-positives)

• interpretation dependent on risk factors

after we inject the PPD, what are we measuring?

the enduration

enduration

thickening of the tissue

what is erythema?

redness of the tissue

Interpretation of PPD

• >= 5 mm: HIV, recent TB contacts, classic X-ray changes, organ transplant

• >= 10 mm: immigration from endemic area within 5 years, IV drug user, residents of high risk congregate settings, microbiology lab worker, CKD/DM/cancer

• >= 15 mm: all others

(the required thickness for people who fall into those categories to be considered positive TB test)

Interferon-gamma release assays (IGRA) TB test

• blood test used to measure immune response to TB

• only one visit needed for the test

• not affected by BCG vaccine

Bacterial culture test for TB

• sputum collection

• takes up to 12 weeks for final reading (needs to be negative for 12 weeks)

• only finds pulmonary TB

First line TB agents

• Rifampin/Rifabutin/Rifapentine

• Isoniazid

• Pyrazinamide

• Ethambutol

“backbone of TB therapy”

Rifampin/Rifabutin/Rifapentine (longer therapy needed if non-rifampin)

Common drugs that interact with Rifampin/Rifabutin/Rifapentine that induce CYP-450

• oral contraceptives

• anti-retroviral agents

• anticonvulsants

Rifampin characteristics

most commonly used in the US

Rifabutin characteristics

fewer drug interactions, commonly used in HIV+ patients (use in patients who take many other drugs)

Rifapentine characteristics

longer duration of action (used in weekly regimens)

How should we administer Rifampin/Rifabutin/Rifapentine?

take 1 hour before or 2 hours after meals because food decreases absorption

ADRs for Rifampin/Rifabutin/Rifapentine

• rash

• mild GI

• hepatotoxicity

• discoloration of body fluids

• pseudomembranous colitis (inflammation in bowels)

Rifampin is commonly used with what other drug?

isoniazid

ADRs of isoniazid

• peripheral neuropathy

  • decrease in B6

• hepatotoxicity

• hyperglycemia

  • see in diabetic patients (not a big deal in non-diabetics)

When is pyrazinamide and ethambutol commonly used?

the initial phase of treatment

ADRs for pyrazinamide

• hepatotoxicity

• GI

• hyperuricemia/gout

• non-gout polyarthralgia

ADRs of ethambutol

• retrobulbar neuritis (red-green colorblindness or visual acuity)

• hepatotoxicity

Which first line TB agent is the least hepatotoxic?

ethambutol

In order to treat TB, you must use a ___ of drugs

combination

Directly observed therapy

a provider or staff member will watch the patient to ensure they take their medications

What type of patient is directly observed therapy recommended for?

• resistant TB

• HIV infected patients

• intermittent regimens (non-daily)

Why is directly observed therapy used?

to maintain excellent adherence

Preferred treatment options for latent TB

• isoniazid & rifapentine weekly for 3 months (most common)

• rifampin daily for 4 months

• daily isoniazid and rifampin for 4 months

Active TB intensive phase treatment

RIF + isoniazid + pyrazinamid +ethambutol for 2 months

Active TB infection continuation phase

• if not resistant: RIF + isoniazid for 4 months

• if resistant: more drugs and longer duration

What is the minimum amount of time you should treat active TB?

6 months

All TB is considered to be ___

resistant (must use at least 2 drugs)

Multidrug-resistant TB (MDR TB) is resistant to which drugs?

isoniazid & rifampin

Extensively drug-resistant TB (XDR TB)

isoniazid, rifampin, and at least 2 other drugs (not seen in US yet)