Tuberculosis Pharm

3 characteristics of mycobacterium

unique cell wall

acid-fast bacilli

slow growing

cell wall component of mycobacterium

mycolic acid

stain used for mycobacterium

acid-fast

countries associated with higher TB rates

Mexico

Haiti

India

Phillipines

Vietnam

3 things that influence probability of TB transmission

infectiousness of person with TB

environment in which the exposure occurred

frequency and duration of exposure

LTBI

latent TB infection

most infected with TB develop what kind of infection?

latent TB

live but inactive TB bacteria in the body

latent TB infection

clinical presentation of latent TB infection

asymptomatic patient NOT contagious

testing results for LTBI

POSITIVE PPD or IGRA

NEGATIVE sputum and CXR

primary progression to active disease is most common in:

infants

children < 5

sevely immunocompromised

most common form of active TB infection

reactivation (LTBI → TB)

most common sites of extrapulmonary TB

lymphatic

pleural

bone/joints

timing of LTBI → TB

most common within first 2 years

what comorbidities increase risk of active TB development

HIV > diabetes

preferred regimens for latent TB

isoniazid + rifapentine

rifampin

isoniazid + rifampin (less evidence)

most common alternative regimen for latent TB

isoniazid monotherapy (6 months preferred)

benefit of isoniazid + rifapentine

higher completion rate

lower hepatoxicity

benefit of rifampin monotherapy

higher completion

lower heptatoxicity

lower discontinuation due to AEs

cons of rifampin monothreapy

limited HIV + evidence

drug drug interactions

objectives of active TB treatment

rapid killing of bacilli

achievement of relapse-free cure

protection against drug resistance

3 reasons for increased resistance

irregular compliance

inadequate drug absorption / dosing

use of single agent therapy

_ have anti-TB activity

respiratory FQs

caution using _ to treat pneumonia while ruling out TB

respiratory FQs

length of intensive phase of active TB treatment

first 8 weeks

3 phases of active TB treatment

intensive

continuation

relapse

number of drugs used in active intensive phase

4

when does active TB relapse occur

when treatment not continued long enough

intensive phase active TB drugs

Rifampin

Isoniazid

Pyrazinamide

Ethambutol

continuation phase active TB drugs

rifampin

isoniazid

length of active TB continuation phase

18 weeks

preferred regimen for newly diagnosed pulmonary TB

RIPE for 8 weeks then RI for 18 weeks

what kind of dosing is preferred for TB

daily

why is daily dosing preferred for active TB

decreases rate of acquired drug resistance

indications for 7 month continuation regimens

HIV patient not received anti-retroviral therapy during TB

patients who didn’t receive pyrazinamide during initial

patients with cavitary pulmonary TB and positive sputum culture after 2 months of treatment

patients with bone/joint/spinal TB or TB meningtits

length of shortened RIPE regimen

4 months

ages that receive shortened RIPE regimen

ages 3 months - 16 yo

non-severe TB

peripheral lymph node TB

intrathoracic lymph node TB w/o airway obstruction

uncomplicated TB pleural effusion

paucibacillary and non-cavitary disease confined to one lobe

regimen timing for shortened active TB therapy

8 weeks of intensive therapy

8 weeks of continuation phase

alternate shortened active TB regimen

8 weeks of: rifapentine

isoniazid

pyrazinamide

moxifloxacin

then discontinue pyrazinamide for the next 8 weeks

what kind of breaks in therapy are more serious

earlier / longer

when is un-interrupted treatment more important

during intesnive therapy

what is more important to assess when evaluating interruptions in TB therapy

total number of doses

when is it necessary to restart treatment from the beginning for active TB treatment during the intensive phase

lapse greater than 14 days

what to do if sputum comes back + after loss of treatment

restart entire regimen

what to do if sputum comes back - after loss of treatment

treat with INH + RIF for 4 months

rifampin MOA

inhibits DNA-dependent RNA polymerase

bactericidal

rifampin adverse effects

reddish-orange discoloration of body fluids

hepatotoxicity (increased bili and ALP)

pruritus ± rash

hypersensitivty (rare)

rifampin is a CYP _

inducer

don’t use _ monotherapy for active TB treatment

rifampin

rifampin alternatives

rifabutin

rifapentine

least potent rifamycin CYP inducer

rifabutin

which rifamycin is better for HIV positive patients receiving protease inhibitors

rifabutin

rank the CYP inducing capacity of the rifamycins

rifampin > rifapentine > rifabutin

drawback of rifapentine

less studied with HIV meds

isoniazid MOA

inhibits mycolic acid synthesis to disrupt cell wall synthesis

is isoniazid bactericidal or bacteriostatic

bactericidal

is rifampin bactericidal or bacteriostatic

bactericidal

isoniazid adverse effects

hepatitis

peripheral neruopathy

supplement needed with isoniazid

pyridoxine (vit B6)

which drug requires vitamin B6 supplementation during therapy

isoniazid

pyrazinamide MOA

unknown

sterilizes semi-dormant / dormant TB

pyrazinamide AE’s

GI effects

hepatotoxicity

asymptomatic hyperuricemia

non-gout polyarthalgias

ethambutol MOA

inhibits arabinosyl transferases = interferes with cell wall formation

is ethambutol bacteriostatic or bacteriocidal

bacteriostatic

ethambutol AE’s

optic neuritis (reversible)

what reduces mortality in HIV patients with TB

earlier initiation of ART

IRIS stands for

immune reconstitution inflammatory syndrome

what kind of TB has highest risk for developing IRIS

TB meningitis

ART recommendation in pregnancy

initiate as early as feasible

ART therapy for TB meningitis

delay for 8 weeks

wait 2 weeks until meningitis under control

ART therapy for TB and low CD4

start within 2 weeks of starting TB treatment

pre-emptive prednisone for risk of IRIS

ART treatment for TB with non-low CD4

start within 2-8 weeks after starting TB treatment

challenges in treating HIV and TB

medication adherence

overlapping side effects

IRIS

drug interaction

primary drug resistance

caused by person-to-person transmission of resistant organisms

what defines multidrug resistant TB

resistant to rifampin and INH

pre-extensively drug resistant TB

resistance to RIF, INH, any FQ

extensively drug resistant TB

resistance to RIF, INH, FQ, and bedaquiline OR linezolid

crucial part of the management of drug resistant TB

contact health department

2nd line drug resistant TB treatment

moxifloxacin

bedaquiline

pretomanid

linezolid

RIF- resistant, FQ resistant treatment

bedaquiline

pretomanid

linezolid

RIF-resistant, FQ susceptible treatment

Bedaquiline

pretomanid

linezolid

moxifloxacin

bedaquline MOA

inhibits mycobacterial ATP synthase required for energy generation

bedaquline bacteriocidal or static?

bactericidal

bedaquiline black box warning

QT prolongation

bedaquline adverse reactions

hepatotoxicity

QT prolongation

CYP3A4

pretomanid MOA

Inhibits mycobacterial cell wall synthesis killing nonreplicating MTB by nitric oxide release

pretomanid bactericidal/bacteristatic

bactericidal

pretomanid AEs (4)

peripheral neuropathy

anemia

GI upset

elevated LFTs

consideration of pretomanid

CYP3A4 substrate

baseline monitoring for all patients taking TB therapy

hepatic enzymes

bilirubin

creatinine

platelets

HIV

A1c

baseline monitoring for patients taking ethambutol

visual acuity and color vision

baseline monitoring for HIV infected patients

CD4+ lymphocyte count

during treatment monitoring for all patients

medication adherence

identification of AE’s

_ monitoring are not recommended during TB therapy unless experiencing symptoms

LFTs

what to measure to manage GI upset adverse effects

ALT and billirubin

when to evaluate for hepatotoxicity

if ALT > 3x upper limit of nomral

recommendations for managing GI upset adverse effect

take meds at bedtime

take with food

consider PPI or H2 agonist if sx’s of gastritis

what to do if patient develops a petechial rash as side effect

check platelets (might be due to rifampin thrombocytopenia, discontinue if so)

what to do if patient develops minor rash as AE

administer antihistamines and continue meds