Drug Treatment for TB

BCG Vaccine

Latent TB

TB treatment in Non HIV Patients

MDR

XDR

TDR
BCG Vaccine
Bacille Calmette-Gurin (BCG) is a vaccine for
tuberculosis
Up to 80% effective in children
Not given to prevent Pulmonary TB in adults
-not widely used in the United States
-given to infants and small children
-not always protective
-Given to TB neg children exposed to adults
with resistant or adults not properly treated
http://www.cdc.gov/tb/topic/vaccines/default.htm


Kernodle, D "Decrease in the Effectiveness of Bacille Calmette-Guerin Vaccine against
Pulmonary Tuberculosis", Clin Infect Dis, 2010, 177 cid.oxfordjournals.org/content/51/2/177.full
NEW VACCINES
20 candidates in the clinical trial pipeline
BCG remains the only vaccine available for TB
In adults FAILS to against transmissible pulmonary
TB
Lack of animal models hinders development.

Maeurer, M. Progress in tuberculosis vaccine development and host-directed therapiesa state
of the art review. <i>The Lancet Respiratory Medicine
Brennan, M. J. Critical research concepts in tuberculosis vaccine development. <i>Clinical
Microbiology and Infection</i>, n/a-n/a..
TB Treatment in HIV-
Same drugs for 40 years
10 drugs currently approved
First Line Agents-
Isoniazid (INH)
Rifampin (RIF)
Rifapentine for latent TB (RPT)
Ethambutol (EMB)
Pyrazinamide (PMZ)
http://www.cdc.gov/tpic/treatment/default.htm
b/to
TB Treatment in HIV-
Same drugs for 40 years
10 drugs currently approved
First Line Agents-
Isoniazid (INH)
Rifampin (RIF)
Rifapentine for latent TB (RPT)
Ethambutol (EMB)
Pyrazinamide (PMZ)
http://www.cdc.gov/tpic/treatment/default.htm
b/to
Instruct client to report side effects specific
to antituberculosis therapy prescribed:
Blurred vision or changes in color or
vision field (ethambutol)
Difficulty in voiding (pyrazinamide)
Fever, yellowing of skin, weakness, and
dark urine (isoniazid, rifampin)
GI system disturbances (rifampin)
Changes in hearing (streptomycin)
Numbness and tingling of extremities
(isoniazid)
Red discoloration of body fluids
(rifampin)
Initial Phase 2 months
Continuation phase
4 months
7 months
7 months for three groups
Cavitary TB w/ + sputum after 2 months tx
Patients who did not take PZA
Patients only treated 1x week w + sputum
Continuation Phase
Four or seven months
Seven months only for 3 groups
Drug susceptible cavitary TB w + sputum after 2
months
Patients who did not take PZA initally
Patients treated 1x/week with + sputum after 2
months
http://www.cdc.gov/tb/topic/treatment/tbdisease.htm#2
ISONIAZID 5 mg/kg PO/IM qDay, not
to exceed 300 mg qDay
Side effects include:
BLACK BOX WARNING severe or fatal
hepatitis.
Nausea, vomiting, weakness, dizziness, slurred
speech, lethargy
Megaloblastic anemia, thrombocytopenia,
lupus, agranulocytosis
Progressive liver damage (increases with age;
2.3% in pts > 50 yo)
http://reference.medscape.com/drug/isoniazid-342564#4
RIFAMPIN 10 mg/kg/day PO or 10 mg/kg PO
twice weekly (directly observed therapy [DOT]);
not to exceed 600 mg/day
Side effects: leukemia in doses over 600mg/wk
Nausea, vomiting, diarrhea, colitis, pancreatitis
Fatigue, weakness, ataxia, numbness,
headache, dizziness, behavioral changes
May decrease the effectiveness of oral
contraceptive pills
Rare renal hypersensitivity if discontinued and
resumed
Red discoloration of urine, tears, sweat
http://reference.medscape.com/drug/rifadin-rimactane-
rifampin-342570#5
ETHAMBUTOL Initial TB treatment: 15
mg/kg PO qDay
Side effects: optic neuritis, blindness
Anorexia, vomiting, malaise, headache, fever
Confusion
Abnormal liver function
Peripheral neuritis
Anaphylaxis
http://reference.medscape.com/drug/myambutol-
ethambutol-342677#4
PYRAZINAMIDE 15-30 mg/kg PO qDay; not
to exceed 2 g/day
Side Effects: Nausea, vomiting, anorexia,
diarrhea, malaise
Photo-sensitivity, gout, dysuria
Gout
Hepatoxicity
Interstitial nephritis

http://reference.medscape.com/drug/pyrazinamide-
342678
Multi-Drug Resistant TB
bedaquiline fumarate (Sirturo)
1
st
New drug in 40 years for TB
Pulmonary MDR TB direct observation (DOT)
Combined with other drugs
BLACK BOX WARNINGS, increased risk of
death (11.4% v 2..5%, Cardiac problems
Hepatotoxicity
Nausea, arthralgia, headache, transamylase,
blood amylase elevation
MDR
Weeks 1-2: 400 mg PO qDay for 2 weeks
Weeks 3-24: 200 mg 3 times/week for 22 weeks
Take with a multidrug regimen consisting of at
least 4 other drugs that the MDR-TB is likely
susceptible for the entire 24 week duration
http://reference.medscape.com/drug/sirturo-bedaquiline-
999799#10
http://www.niaid.nih.gov/topics/tuberculosis/Understanding/WhatIsTB/Visu
alTour/pages/mdr-tb.aspx
XDR-Extremely Drug Resistant TB
resistant to isoniazid, rifampin, any
fluoroquinolone, and at least one of 3 injectable
second-line drugs (ie, amikacin, kanamycin, or
capreomycin).
XDR-TB resistant to all anti-TB drugs tested
has been reported in Italy, Iran, and India.
Same treatment as MDR
cure is possible for an estimated 30% to 50%
http://www.cdc.gov/tb/publications/factsheets/drtb/x
drtb.htm
Drug Treatment for HIV+ w TB
simultaneous treatment for both
TB) is the leading cause of death for HIV+
worldwide
430,000 TB deaths of HIV+ coinfected
Daily Treatment
Dose reduction may be needed with ART
http://www.treatmentactiongroup.org/tb/background
http://www.euro.who.int/en/health-topics/communicable-
diseases/tuberculosis/publications/2013/2013-revision-protocol-
4.-management-of-tuberculosis-and-hiv-coinfection
TB Tx OF CHILDREN

Isoniazid: 10 mg/kg/day (1015 mg/kg/day)
Rifampicin: 15 mg/kg/day (1020 mg/kg/day)
Pyrazinamide: 35 mg/kg/day (3040
mg/kg/day)
Ethambutol: 20 mg/kg/day (1525 mg/kg/day

Cannot use fixed dose combination products
because dose not correct for children
No date for pediatric dosing for MDR

http://www.who.int/childmedicines/tuberculosis/en/
http://www.treatmentactiongroup.org/tagline/20
13/spring/tb-drugs-children
OBSTACLES
Metabolism different
Dosages not formulated or children
Pills too hard to swallow
:Liquid/pediatric formulations not available
Combination Drugs not formulated in child
dosages
99% cure for non MDR w basic protocol
Failure rate high due to non-adherence



http://www.treatmentactiongroup.org/tagline/20
13/spring/tb-drugs-children