Incidence of TB
• 1/3 of world’s population have TB.
• 9 million TB illnesses worldwide/year.
• 2 million TB-related deaths/year.
• 4.4 TB cases per 100,000 persons in
2007 (13,293 cases reported).
• 644 TB deaths in 2006.
• Overall TB rate has been declining in
Overview of TB
• Caused by Mycobacterium tuberculosis
• Airborne transmission via inhalation of droplet
nuclei containing tubercle bacilli
• 5% of infected patients develop disease within
2 years, another 5% develop disease in
• Primarily pulmonary disease: coughing
• Extrapulmonary TB: lymph nodes, meninges,
bones, pleura, kidneys
• Miliary TB: generalized infection, rare but
serious, “millet seed” appearance on CXR
High Risk for contracting High Risk for developing
TB Infection TB disease
• Exposure to known or • Medical conditions (e.g.
suspect TB HIV, diabetes, silicosis,
• emmigration from high cancer, organ transplant,
incidence country (e.g. immunosuppressives/
Asia, Africa) anti-TNF therapy)
• Injectable illegal drug • Infants & children < 4
use years old.
• High-risk settings (e.g. • Recent TB infection in
LTCF, correctional last 2 years.
Consider Treatment Initiation if:
• Positive AFB smear, epidemiological,
clinical symptoms, pathological findings.
Do not delay treatment because of negative
AFB smears if high suspicion:
• History of cough & weight loss
• Characteristic findings on CXR
• Emmigration from high-incidence country
When can I consider Rifapentine
(RPT) in Continuation Phase?
• Patient is HIV negative
• Has non-cavitary pulmonary TB
• Negative sputum smears at 2 month initial phase
INH + RPT once weekly for 4 months (by DOT)
If culture positive at end of initial phase:
INH + RPT once weekly for 7 months (by DOT)
Treatment of Culture Positive TB
(Rated BI for HIV negative, BII for HIV positive)
2 months: INH, RIF, PZA, EMB 3x/week (24 doses, 8 weeks)
1) 4 months: INH + RIF 3x/week (54 doses, 18 weeks)
2) 7 months: INH + RIF 3x/week (93 doses, 31 weeks)
Regimens without Pyrazinamide
(Rated CI for HIV negative, CII for HIV positive)
2 months: INH, RIF, EMB daily (56 doses, 8 weeks)
1) 7 months: INH + RIF daily (217 doses, 31 weeks)
2) 7 months: INH + RIF twice/week (62 doses, 31 weeks) *
*Twice weekly not recommended for patients with CD4+ count <100/µL
When to extend continuation
phase to 7 months?
• Cavitary pulmonary disease and
positive sputum cultures at end of 2
month initiation phase
• Initial phase did not contain PZA
• Patients taking once weekly
INH+rifapentine and positive 2 month
• Inactive tubercle bacilli. Noninfectious.
• At high risk for progression to active TB
Diagnosis: Positive PPD. Asymptomatic.
Normal CXR, negative sputum smears &
Preferred INH daily or twice/week (DOT) for 9
Alternative RIF daily for 4 months (adults), 6
• Sputum for AFB smear & culture every month
(until 2 consecutive negative cultures)
• Drug susceptibility testing on initial positive
• HIV & Hep B/C (if high risk) when tx initiated
• CXR: at 2 month initiation phase if initial
negative cultures OR at end of treatment for
culture negative TB
• Baseline serum creatinine, AST/ALT, bilirubin,
alk phosphatase, platelets
• Visual acuity & color vision monthly if EMB
treatment longer than 2 months or receiving
greater than recommended mg/kg doses
ADVERSE EFFECTS OF TB DRUGS
DRUG ADVERSE EFFECTS MONITORING
Isoniazid • Hepatotoxicity, lupus-like syndrome, • LFTs, flushing,
peripheral neuropathy tingling in hands &
• Monoamine toxicity feet.
Rifampin • GI upset, hepatotoxicity, flu-like • Baseline LFTs,
syndrome, hemolytic anemia, CBC, SCr, clinical
thrombocytopenia, renal failure, symptoms. LFTs
orange-discoloration of body fluids. monthly if abnorm
• Drug interactions: potent enzyme baseline or ↑ risk for
Pyrazinamide • Hepatoxocity, hyperuricemia, • Basline LFTs, SCr
arthralgias, GI upset, rash • Uric acid if
Ethambutol • Optic neuritis (blurred vision, • Baseline & monthly
scotomata “blind spot”, red-green visual acuity & color
color blindness), hyperuricemia vision, SCr.
TB DRUG RESISTANCE
Multi-drug resistant TB (MDR-TB): resistant to INH & RIF.
Extensively drug-resistant TB (XDR-TB): resistant to INH,
RIF, fluoroquinolone & injectables (aminoglycosides,
• Never add single new agent to failing regimen.
• Always attempt to add at least 3 unused drugs (1 should
be injectable) with in vitro susceptibility.
• Request expert consultation.
• DOT strongly recommended.
• Cross-resistance between RIF, rifabutin and rifapentine.
• No cross-resistance between SM & other injectables.
• Cross-resistance between amikacin & kanamycin.
• Monoresistance to PZA is uncommon (consider M. bovis)
• Blumberg HM, Burman WJ, Chaisson RE et al. American
Thoracic Society/Centers for Disease Control and
Prevention/Infectious Diseases Society of America:
Treatment of Tuberculosis. Am J Respir Crit Care Med
• Blumberg HM, Leonard MK, Jasmer RM. Update on the
Treatment of Tuberculosis and Latent Tuberculosis Infection.
• Centers for Disease Control and Prevention. Trends in
tuberculosis incidence-United States, 2007. MMWR Morb
Mortal Wkly Rep. 2008;57(11):281-285.
• Inge L, Wilson JW. Update on the Treatment of
Tuberculosis. Am Fam Physician 2008;78(4):457-465.