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Core Curriculum > Chapter 7
Core Curriculum on Tuberculosis, 2000
Chapter 7
Treatment of TB Disease
Regimens
Drug-Resistant TB
(See table 3)
A 6-month regimen of isoniazid, rifampin, pyrazinamide, and either
ethambutol or streptomycin has been demonstrated to be effective
for the treatment of TB resistant only to isoniazid. 18
When resistance to isoniazid is documented during the recommended
initial four-drug therapy, the regimen should be adjusted by discontinuing
isoniazid and continuing the other three drugs for the entire 6
months of therapy. TB resistant only to isoniazid may also be treated
with rifampin and ethambutol for 12 months. 19
When isoniazid resistance is documented in the 9-month regimen
without pyrazinamide, isoniazid should be discontinued. If ethambutol
was included in the initial regimen, treatment with rifampin and
ethambutol should be continued for a minimum of 12 months. If ethambutol
was not included initially, susceptibility tests should be repeated,
isoniazid should be discontinued, and two other drugs, to which
the isolate is susceptible (e.g., ethambutol and streptomycin),
should be added. The regimen can be adjusted when the results of
the susceptibility tests become available.
Multidrug-resistant TB (i.e., TB resistant to at least isoniazid
and rifampin) presents difficult treatment problems. Treatment must
be individualized and based on the patient’s medication history
and susceptibility studies.
Unfortunately, adequate data are not available on the effectiveness
of various regimens and the necessary duration of treatment for
patients with organisms resistant to both isoniazid and rifampin.
Moreover, many of these patients also have resistance to other first-line
drugs (e.g., ethambutol and streptomycin) when drug resistance is
discovered. Because of the poor outcome in such cases, it is preferable
to give at least three new drugs to which the organism is susceptible.
This regimen should be continued until culture conversion is documented,
followed by at least 12 months of two-drug therapy. Often, a total
of 24 months of therapy is given empirically. Some experts recommend
that at least 18-24 months of three-drug therapy be given after
culture conversion. 20
MDR TB should be treated using a daily regimen under direct observation
(DOT). Intermittent administration of medications is not possible
in treatment of MDR TB.
Clinicians who are unfamiliar with the treatment of drug-resistant
TB should seek expert consultation. Because second-line drugs can
cause serious adverse reactions, patients taking these drugs should
be monitored closely throughout the course of treatment. The role
of agents such as the quinolone derivatives and amikacin in the
treatment of multidrug-resistant disease is not well characterized,
although these drugs are commonly being used in such cases. Surgery
may offer considerable benefit and a significantly improved cure
rate for patients who have multidrug-resistant TB if the bulk of
disease can be resected. 21
However, drug therapy is usually required to sterilize the remaining
disease.
TB Treatment for HIV-Positive Patients with Drug-Resistant TB
TB disease resistant to isoniazid only. The treatment regimen
should generally consist of a rifamycin (rifampin or rifabutin),
pyrazinamide, and ethambutol for the duration of treatment. Because
the development of acquired rifamycin resistance would result in
MDR TB, clinicians should carefully supervise and manage TB treatment
for these patients.
TB disease resistant to rifampin only. The 9-month treatment
regimen should generally consist of an initial 2-month phase of
isoniazid, streptomycin, pyrazinamide, and ethambutol. The second
phase of treatment should consist of isoniazid, streptomycin, and
pyrazinamide administered for 7 months. Because the development
of acquired isoniazid resistance would result in MDR TB, clinicians
should carefully supervise and manage TB treatment for these patients.
Multidrug-resistant TB (resistant to both isoniazid and rifampin).
These patients should be managed by or in consultation with physicians
experienced in the management of MDR TB. Most drug regimens currently
used to treat MDR TB include an aminoglycoside (e.g., streptomycin,
kanamycin, amikacin) or capreomycin, and a fluoroquinolone, along
with other agents to which the organism is sensitive. The recommended
duration of treatment for MDR TB in HIV-positive patients is 24
months after culture conversion, and posttreatment follow-up visits
to monitor for TB relapse should be conducted every 4 months for
24 months. Because of the serious personal and public health concerns
associated with MDR TB, health departments should always use DOT
for these patients and take whatever steps are needed to ensure
their adherence to the treatment regimen.
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