In order for people with drug-resistant TB
to be cured, they need to be given TB drugs which they are not resistant to. Treatment
regimens for drug-resistant TB will be different from country to country or
programme to programme depending on the resources available. There are three
ways of designing a TB drug regimen for drug-resistant TB.
surveillance data from representative patient populations are used to design a
treatment regimen that is most likely to cure people with drug-resistant TB in
the area. This is done especially in countries and programmes where individual
drug-sensitivity testing (DST) is not available due to a lack of funds or
capacity in the laboratories.
is when each regimen is designed for the person with drug-resistant TB based on
their previous history of anti-TB treatment. In this case, people will be given
a second-line regimen which does not include the anti-TB treatment which they
have been exposed to previously and may have developed resistance to. The
drug-resistance surveillance data of the population which the patient comes
from are also considered.
In cases where an empirical
regimen is used, it is usually adjusted when drug-resistance testing results on
the individual patient become available.
In individualised treatment the patient’s drug-resistant TB regimen is designed based on their previous
history of anti-TB treatment and individual drug-sensitivity results.
The recommended time for treatment of
drug-resistant TB is guided by culture conversion. In the treatment of patients
with MDR-TB, an intensive phase of 8 months is suggested for most patients. In
patients not previously treated for MDR-TB, a total treatment duration of 20
months is suggested for most. The duration of intensive and continuation phases
of treatment may be modified according to the patient’s response to therapy. In
the treatment of patients with MDR-TB, four second-line anti-TB drugs
likely to be effective (including a parenteral agent), as well as pyrazinamide,
are included in the intensive phase. Regimens need to include at least
pyrazinamide, a later-generation fluoroquinolone, a parenteral agent,
ethionamide (or prothionamide), and either cycloserine (or terizidone) or PAS
(p-aminosalicylic acid) if cycloserine cannot be used.
a treatment regimen for MDR-TB
- Step 1: Begin with any first-line TB drug
regimen that has certain, or almost certain, efficacy. If a first-line drug
has a high likelihood of resistance, do not use it. Use a first-line oral agent
drug which is available, namely ethambutol or pyrazinamide.
- Step 2: Add an injectable agent (kanamycin,
amikacin or capreomycin) based on DST and treatment history. Streptomycin
should not be used, even if DST suggests susceptibility, because of high rates
of resistance with DR-TB strains and higher incidence of ototoxicity (damage to
the ear and hearing loss).
- Step 3: Add a fluoroquinolone
(levofloxacin, moxifloxacin or ofloxacin) based on DST and treatment history.
- Step 4: Add second-line oral bacteriostatic
agent drugs (cycloserine or terizidone, ethionamide or prothionamide, or PAS)
until there are at least four second-line drugs likely to be effective. This
choice should be based on treatment history, adverse effect profile,
availability and cost.
Consider adding Group 5 drugs (clofazimine,
linezolid, amoxicillin, clavulanate, thioacetazone, imipenem/cilastatin,
high-dose isoniazid or clarithromycin) if there are not four second-line drugs
that are likely to be effective from steps one to four. The anti-TB activity of
many of these drugs is unclear. If drugs are needed from this group, it is recommended
to add at least two, as anti-TB DST is not reliable for the drugs in this
- Step 1: Use any of the first-line anti-TB
drugs that may be effective (ethambutol or pyrazinamide).
- Step 2: Use an injectable agent to which
the strain is susceptible and consider an extended duration of use (12 months
or possibly the whole treatment). If resistant to all injectable agents, it is
recommended to use one the patient has never used before.
- Step 3: Use a later-generation
fluoroquinolone such as moxifloxacin.
- Step 4: Use both ethionamide (or
prothionamide) and cycloserine (or terizidone) if they have not been used
extensively in a previous regimen or any that are likely to be effective.
- Step 5: Use two or more drugs from Group 5
(clofazimine, linezolid, amoxicillin, clavulanate, thioacetazone,
imipenem/cilastatin, high-dose isoniazid or clarithromycin).
- Step 6: Consider high-dose isoniazid treatment
if low-level resistance to this agent is documented.
Pregnant women can and should be treated
for drug-resistant TB. Treatment for drug-resistant TB should be started in the
second trimester, or sooner if the condition of the woman is severe. Avoid
injectable agents. For the most part, aminoglycosides should not be used in the
regimens of pregnant women and can be particularly toxic to the developing
foetal ear. Capreomycin may carry the same risk of ototoxicity, but is the drug
of choice if an injectable agent cannot be avoided. Ethionamide should be
avoided as it can increase the risk of nausea and vomiting associated with
of MDR-TB in people living with HIV
Antiretroviral therapy (ART) use during treatment with second-line
TB drugs improves cure rates and decreases risk of death among MDR-TB patients
living with HIV. ART should be started as early as possible, regardless of CD4
counts, in all MDR-TB patients living with HIV. Second-line anti-tuberculosis
treatment should be initiated first, followed by ART as soon as possible within
the first 8 weeks of treatment. This is especially important in those HIV-positive
TB patients with profound immunosuppression (e.g. CD4 counts less than 50 cells
cells/mm3), who should receive ART immediately within the first two weeks of
initiating TB treatment.
Although the use of ART in combination with
second-line anti-tuberculosis drugs can increase the pill burden for the
people in your care, potentially resulting in lower rates of adherence, there is limited
evidence of increased risk of adverse events among people receiving the
combined treatment compared with people who do not receive ART. It may be
necessary to consider overlapping adverse events or toxicities when deciding
particular combinations of ARV and second-line TB drugs.
MDR-TB patients living with HIV should receive a comprehensive package
of HIV care, including prevention, diagnosis, treatment and care interventions.
Cotrimoxazole preventive therapy (CPT) should be
provided as part of a comprehensive package of HIV care. In addition, regular monitoring of treatment
response, care for opportunistic infections, provision of safe water,
sanitation and hygiene, nutritional and psychosocial support should be
provided. Client-centred and integrated TB and HIV
services should be provided for MDR-TB patients living with HIV at the same
place and time as much as possible. Retention of patients in HIV care and ART
should be ensured for all patients after completion of TB treatment.