DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

employees of high-risk congregate settings. Any person with a skin
test >15 mm is also at high risk of disease. In these patients at high
risk of active TB, prophylaxis is recommended to prevent active disease.
Prophylaxis consists of oral isoniazid, 300 mg daily or twice
weekly, for 6 months in adults. Those who cannot take isoniazid
should be given rifampin, 10 mg/kg daily, for 4 months. In children,
isoniazid 10-15 mg/kg daily (maximum 300 mg) is administered, or
20-30 mg/kg two times a week directly observed, for 9 months. In
children who cannot tolerate isoniazid, rifampin 10-20 mg/kg daily
for 6 months is recommended.
Definitive Therapy. All active TB cases should be confirmed
by culture and have antimicrobial susceptibilities
determined. The current standard regimen for drugsusceptible
TB consists of isoniazid (5 mg/kg, maximum
300 mg/day), rifampin (10 mg/kg, maximum 600 mg/day),
and pyrazinamide (15-30 mg/kg, maximum of 2 g/day)
for 2 months, followed by intermittent 10 mg/kg rifampin
and 15 mg/kg isoniazid two or three times a week for
4 months. Children should receive 10-20 mg/kg isoniazid
per day (300 mg maximum). Rifabutin 5 mg/kg/day
can be used for the entire 6 months of therapy in adult
HIV-infected patients because rifampin can adversely
interact with some antiretroviral agents to reduce their
effectiveness. In case there is resistance to isoniazid,
initial therapy also may include ethambutol (15-20
mg/kg/day) or streptomycin (1 g/day) until isoniazid
susceptibility is documented. Ethambutol doses in
children are 15-20 mg/kg/day (maximum 1 g) or 50
mg/kg twice weekly (2.5 g). Because monitoring of
visual acuity is difficult in children <5 years old, caution
should be exercised in using ethambutol in these
children.
The first 2 months of the four-drug regimen is termed the
initial phase of therapy, and the last 4 months the continuation phase
of therapy. Rifapentine (10 mg/kg once a week) may be substituted
for rifampin in the continuation phase in patients with no evidence
of HIV infection or cavitary TB. Pyridoxine, vitamin B 6
, (10-50
mg/day) should be administered with isoniazid to minimize the
risks of neurological toxicity in patients predisposed to neuropathy
(e.g., the malnourished, elderly, pregnant women, HIV-infected
individuals, diabetic patients, alcoholic patients, and uremic
patients). To ensure compliance, therapy is administered as directly
observed therapy (DOT). Although DOT is the standard of care, an
analysis of a series of 11 randomized clinical trials found no difference
in outcome between DOT and self-administered therapy
(Volmink and Garner, 2007).
The duration of therapy for drug-susceptible pulmonary TB
is 6 months. A 9-month duration should be used for patients with
cavitary disease who are still sputum culture positive at 2 months.
HIV-infected patients with CD4+ lymphocyte cell counts <100/mm 3
are at increased risk of developing rifamycin resistance. Therefore,
daily therapy is recommended during the continuation phase. Most
cases of extrapulmonary TB are treated for 6 months. TB meningitis
is an exception that requires a 9- to 12-month duration. In addition,
corticosteroids are recommended for TB pericarditis, and results of
a meta-analysis suggest they should also be used in TB meningitis
(Prasad and Singh, 2008).
Drug-Resistant TB. According to the fourth global
report of the World Health Organization (WHO), from
2002 to 2006, the proportion of new TB cases resistant
to at least one anti-TB drug was 17%; isoniazid resistance
was 10%, and MDR (multidrug resistant) was 3%.
MDR-TB is said to be present if an isolate is resistant
simultaneously to isoniazid and rifampin. According to
the CDC, in the U.S., resistance to isoniazid was 8%
and MDR was 1%. In previously treated patients, resistance
to at least one drug was 35%, isoniazid resistance
was 28%, and MDR was 15%; resistance to isoniazid in
previously treated cases was 13%, and MDR was 4%;
of the MDR, only 3% was extensively drug resistant
TB [XDR]. XDR-TB is MDR-TB that is also resistant
to fluoroquinolones and at least one of three injectable
second-line drugs (i.e., amikacin, kanamycin, or capreomycin).
In documented drug resistance, therapy should be based on
evidence of susceptibility and should include:
• at least three drugs to which the pathogen is susceptible, with at
least one of the injectable anti-TB agents
• in the case of MDR-TB, use of four to six medications for better
outcomes
• at least 18 months of therapy (Blumberg et al., 2003; Orenstein
et al., 2009)
The addition to the regimen of a fluoroquinolone and surgical
resection of the main lesions have been associated with improved
outcome (Chan et al., 2004). There are currently no data to support
intermittent therapy.
PRINCIPLES OF THERAPY AGAINST
MYCOBACTERIUM AVIUM COMPLEX
The Mycobacterium avium complex (MAC) is made up
of at least two species: M. intracellulare and M. avium.
M. intracellulare causes pulmonary disease often in
immunocompetent individuals. M. avium is further
divided into a number of subspecies: M. avium subsp.
hominissuis causes disseminated disease in immunocompromised
patients, M. avium subsp. paratuberculosis
has been implicated in the etiology of Crohn’s
disease, and M. avium subsp. avium causes TB of birds.
These bacteria are ubiquitous in the environment and
can be encountered in water, food, and soil. Therefore,
when MAC bacteria are isolated from a nonsterile site
in patient’s body, one cannot assume they are causing
an infection.
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CHAPTER 56
CHEMOTHERAPY OF TUBERCULOSIS, MYCOBACTERIUM AVIUM COMPLEX DISEASE, AND LEPROSY