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Treatment of Drug-Resistant Tuberculosis

WHO has recommended the following for the susceptibility and response monitoring of MDR-TB Treatment:

  • Rapid drug susceptibility testing (DST) of isoniazid and rifampicin or of rifampicin alone is recommended over conventional testing or no testing at the time of diagnosis of TB(subject to available resources
  • The use of sputum smear microscopy and culture rather than sputum smear microscopy alone is recommended for the monitoring of patients with MDR-TB during treatment

General principles for Designing MDR-TB Treatment Regimens

General principles for Designing MDR -TB Treatment Regimens
Principle 1: Use At Least 4 Drugs Certain To Be Effective
The more factors are present, the more likely the drug to be effective
Resistance to these drugs is known from surveys to be rare in similar patients.
DST results show susceptibility to drugs for which there is good laboratory reliability: Injectable agents and Fluoroquinolones.
The drug is not commonly used in the area.
No prior history of treatment failure with the drug.
No known close contacts with resistance to the drug.
Principle 2: Do Not Use Drugs For Which There Is The Possibility Of Cross-Resistance
Many antituberculosis agents exhibit cross-resistance both within and across drug classes
Principle 3: Eliminate Drugs That Are Not Safe
Quality of the drug is unknown.
Known severe allergy or unmanageable intolerance; high risk of severe adverse drug effects such as renal failure, deafness, hepatitis, depression and/or psychosis.)
Principle 4: Include Drugs Groups 1–5 In a Herarchical Order Based On Potency
Use any of the first-line oral agents (Group 1) that are likely to be effective.
Use an effective aminoglycoside or polypeptide by injection (Group 2)
Use a fluoroquinolone (Group 3).
Use the remaining Group 4 drugs to complete a regimen of at least four effective drugs.
For regimens with fewer than four effective drugs, consider adding two (Group 5) drugs. The total number of drugs will depend on the degree of uncertainty, and regimens often contain five to seven.

Drugs Groups for Treatment of MDR-TB

  • Anti-TB drugs are grouped according to efficacy, experience of use and drug class.
  • All the first-line anti-TB drugs are in (Group 1), except streptomycin, which is classified with the other injectable agents in (Group 2).
  • All the drugs in Groups 2–5 (except streptomycin) are second-line, or reserve, drugs.
  • The features of the cross-resistance means that resistance mutations (in M. tuberculosis bacteria) to one anti-TB drug may confer resistance to some or all of the members of the drug family of the same group and less commonly to other members of different drug groups (1).
Drugs Groups for MDR-TB
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: Fluoroquinolones
Levofloxacin (Lfx)
Moxifloxacin(Mfx)
Ofloxacin (Ofx)
Group 4: Oral Bacteriostatic Second-Line Agents
Para-amino salicylic 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)
Clarithromycin(Clr)