Clinical Pharmacy
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Tuberculosis is caused by M. tuberculosis, an
aerobic, non–spore-forming bacillus that resists
decolorization by acid alcohol after staining with
basic fuchsin. For this reason, the organism is often
referred to as an acid-fast bacillus (AFB).
It is also different from other organisms in that it
replicates slowly once every 24 hours instead of
every 20 to 40 minutes as do some other organisms.
M. tuberculosis thrives in environments where the
oxygen tension is relatively high, such as the apices
of the lung, the renal parenchyma, and the growing
ends of bones.
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Mycobacterium tuberculosis is transmitted through
the air by aerosolized droplet nuclei that are
produced when a person with pulmonary or
laryngeal TB coughs, sneezes, speaks, or sings.
These droplet nuclei, which contain one to three M.
tuberculosis organisms, are small enough (1–5 µg)
to remain airborne for long periods of time and
reach the alveoli within the lungs when inhaled.
Tubercle bacilli are not transmitted on inanimate
objects such as dishes, clothing, or bedding, and
organisms deposited on skin or intact mucosa do
not invade tissue.
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Latent Infection versus Active Disease
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A clear distinction should be made between
latent infection and active disease (tuberculosis).
Latent infection occurs when the tubercle bacilli
are inhaled into the body.
After inhalation, the droplet nuclei containing M.
tuberculosis settle into the bronchioles and
alveoli of the lungs.
Development of infection in the lung is
dependent on both the virulence of the organism
and the inherent microbicidal ability of the
alveolar macrophages.
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In the nonimmune (susceptible) host, the bacilli
initially multiply unopposed by normal host
defense mechanisms.
The organisms are then taken into alveolar
macrophages by phagocytosis and may remain
viable, multiplying within the cells for extended
periods of time.
After 14 to 21 days of replication, the tubercle
bacilli spread via the lymphatic system to the
hilar lymph nodes and through the bloodstream
to other organs.
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In most patients, active TB disease results from
reactivation of a previously controlled latent
infection, termed reactivation tuberculosis.
Approximately 10% of individuals who acquire
TB infection and do not receive therapy for the
latent infection will develop active TB disease.
The risk of developing active disease is highest
in the first 2 years after infection, when half of
the cases occur.
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The annual and lifetime risks for reactivation TB have
been shown, however, to be directly related to the size
of the induration on tuberculin skin testing.
The risks for reactivation TB were greater in patients
with larger induration diameters.
The ability of the host to respond to M. tuberculosis
may also be reduced by certain diseases such as
diabetes mellitus, silicosis, chronic renal failure, and
diseases or drugs associated with immunosuppression
(e.g., HIV infection, antitumor necrosis factor-α
agents, organ transplantation, corticosteroids, and
other immunosuppressive agents).
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The overall goals for the treatment of TB are to
cure the patient and to minimize the transmission
of M. tuberculosis to others.
The primary goals of antituberculosis
chemotherapy are to kill the tubercle bacilli
rapidly, prevent the emergence of drug resistance,
and eliminate persistent bacilli from the host's
tissues to prevent relapse.
To accomplish these goals, it is essential that
treatment be tailored and supervision be based on
each patient's clinical and social circumstances
(patient-centered care).
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Effective treatment of TB requires a substantial
period (minimum 6 months) of intensive drug
therapy with at least two bactericidal drugs that
are active against the organism.
The initial phase of treatment is crucial for
preventing the emergence of resistance and for
the ultimate outcome of TB therapy.
Four basic regimens are recommended for the
treatment of adult patients with TB caused by
organisms that are known or presumed to be
drug susceptible.
Initial Phase
Regimen
1
Interval and Doses (Minimal
Drugs
Duration)
INH, RIF, PZA, EMB 7 days/week for 56 doses (8 weeks)
OR 5 days/week for 40 doses (8
weeks)d
Continuation Phase
Interval and Dosesc (Minimal
Drugs
Duration)
INH/RIF 7 days/week for 126 doses (18 weeks)
OR
5 days/week for 90 doses (18 weeks)d
INH/RIF Twice weekly for 36 doses (18 weeks)
INH/RPT Once weekly for 18 doses (18 weeks)
2
3
4
INH, RIF, PZA, EMB 7 days/week for 14 doses (2 weeks)
then twice weekly for 12 doses (6
weeks) OR 5 days/week for 10 doses
(2 weeks)d then twice weekly for 12
doses (6 weeks)
INH, RIF, PZA, EMB Three times weekly for 24 doses (8
weeks)
INH, RIF, EMB
7 days/week for 56 doses (8 weeks)
OR 5 days/week for 40 doses (8
weeks)d
INF/RIF Twice weekly for 36 doses (18 weeks)
INH/RPT Once weekly for 18 doses (18 weeks)
INH/RIF Three times weekly for 54 doses (18
weeks)
INH/RIF 7 days/week for 217 doses (31 weeks)
OR
5 days/week for 155 doses (31
weeks)d
INH/RIF Twice weekly for 62 doses (31 weeks)
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First line agents
 Isoniazid
 Rifampin
 Rifabutin
 Rifapentine
 Ethambutol
 Pyrazinamide
 Streptomycin
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Second-Line Agents
 Cycloserine
 Ethionamide
 Amikacin
 Capreomycin
 Para-aminosalicylic
acid (PAS)
 Levofloxacin
 Moxifloxacin
 Gatifloxacin
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DOT is the practice of a health care provider or other
responsible person observing as the patient ingests and
swallows the TB medications.
DOT is the preferred core management strategy for all
patients with TB.
The purpose of DOT is to ensure adherence to TB therapy.
DOT not only ensures completion of therapy, but it may also
reduce the risk of developing drug resistance. By improving
these two factors, it also reduces the risk to the community.
DOT can be administered with daily or two- to three-timesper-week regimens. It can be administered to patients in the
office or clinic setting, or it be given at the patient's home,
school, work, or other mutually agreed on place.
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Treatment of latent TB infection is effective in
preventing active TB disease in persons who
have positive tuberculin skin tests and in those
at risk for reactivation of active TB.
It is usually with daily INH alone for 6 months
or RIF & INH for 3 months.