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Treatment of Tuberculosis Guidelines

Treatment of Tuberculosis Guidelines

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For MDR treatment, anti-TB drugs are grouped according to efcacy, experience of
use and drug class (Table 7.1). All the frst-line anti-TB drugs are in Group 1, except
streptomycin, which is classifed with the other injectable agents in Group 2. All the
drugs in Groups 2–5 (except streptomycin) are second-line, or reserve, drugs. Te
features of the drugs within each group, including cross-resistance, are discussed in
more detail below. Cross-resistance means that resistance mutations (in M. tuberculo-
sis bacteria) to one anti-TB drug may confer resistance to some or all of the members
of the drug family and, less commonly, to members of diferent drug families (1).

Group 1. Group 1 drugs are the most potent and best tolerated. If there is good labo-
ratory evidence and clinical history that suggests that a drug from this group is ef-
fective, it should be used. If a Group 1 drug was used in a previous regimen that
failed, its efcacy should be questioned even if the DST result suggests susceptibility.
Te newer rifamycins, such as rifabutin, have very high rates of cross-resistance to

Group 2. All patients should receive a Group 2 injectable agent if susceptibility is
documented or suspected. Among aminoglycosides, kanamycin or amikacin is the
frst choice of an injectable agent, given the high rates of streptomycin resistance in
drug-resistant TB. In addition, both these agents are inexpensive, cause less otox-
icity than streptomycin, and have been used extensively for the treatment of drug-
resistant TB. Amikacin and kanamycin are considered to be very similar and have a
high frequency of cross-resistance. If an isolate is resistant to both streptomycin and
kanamycin, or if DRS data show high rates of resistance to amikacin and kanamycin,
capreomycin (a polypeptide) should be used.

Group 3. All patients should receive a Group 3 medication if the M. tuberculosis
strain is susceptible or if the agent is thought to have efcacy. One of the higher gen-
eration fuoroquinolones, such as levofoxacin or moxifoxacin, is the fuoroquinolo-
ne of choice. Ciprofoxacin is no longer recommended to treat drug-susceptible or
drug-resistant TB.

Group 4. Ethionamide (or protionamide) is ofen added to the treatment regimen
because of its low cost. If cost is not a constraint, p-aminosalicylic acid (PAS) may be
added frst, given that the enteric-coated formulas are relatively well tolerated and that


7. TrEaTmEnT of druG-rESISTanT TubErCuloSIS

there is no cross-resistance to other agents. When two agents are needed, cycloserine
can be added. Since the combination of ethionamide (or protionamide) and PAS of-
ten causes a high incidence of gastrointestinal side-efects and hypothyroidism, these
agents are usually used together only when three Group 4 agents are needed: ethion-
amide (or protionamide), cycloserine and PAS. Terizidone can be used instead of
cycloserine and is assumed to be equally efcacious.

Group 5. Group 5 drugs are not recommended by WHO for routine use in drug-
resistant TB treatment because their contribution to the efcacy of multidrug regi-
mens is unclear. Tey can be used in cases where it is impossible to design adequate
regimens with the medicines from Groups 1–4, such as in patients with XDR-TB.
Tey should be used in consultation with an expert in the treatment of drug-resistant

Table 7.1 groupS of drugS To TreAT mdr-TBa


drugs (abbreviations)

Group 1:

first-line oral agents

• pyrazinamide (Z)
• ethambutol (e)
• rifabutin (rfb)

Group 2:

injectable agents

• kanamycin (Km)
• amikacin (Am)
• capreomycin (cm)
• streptomycin (S)

Group 3:


• levofoxacin (lfx)
• moxifoxacin (mfx)
• ofoxacin (ofx)

Group 4:

oral bacteriostatic second-line

• para-aminosalicylic acid (pAS)
• cycloserine (cs)
• terizidone (Trd)
• ethionamide (eto)
• protionamide (pto)

Group 5:

Agents with unclear role in
treatment of drug resistant-TB

• clofazimine (cfz)
• linezolid (lzd)
• amoxicillin/clavulanate (Amx/clv)
• thioacetazone (Thz)
• imipenem/cilastatin (ipm/cln)
• high-dose isoniazid (high-dose H)b
• clarithromycin (clr)


Adapted from Table 7.1 and figure 7.2 of reference 1.


High-dose isoniazid is defned as 16–20 mg/kg/day. Some experts recommend using high-dose
isoniazid in the presence of resistance to low concentrations of isoniazid (>1% of bacilli resistant to
0.2 µg/ml but susceptible to 1 µg/ml of isoniazid), whereas isoniazid is not recommended for high-
dose resistance (>1% of bacilli resistant to 1 µg/ml of isoniazid) (1).


TrEaTmEnT of TubErCuloSIS: GuIdElInES

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