Principles in Designing Treatment for a Patient with

MDR/XDR-TB
Prof. Jose A. Caminero, MD; Ignacio Monedero, MD, MPH; Dr. Anna Scardigli, MD, DHA,
The Union
STEPS
1. Diagnosis

2. Number of drugs
3. Drug selection

4. Length of TB
treatment

5. Surgery
6. Ideal regimen

CONSIDERATIONS
-Analyse the following information:
o Medication History: at least one month of monotherapy or
adding one drug to a failing regimen is a strong predictor
of resistance.
o DST: Most reliable for R and H; less reliable for SLDI and
Fq; not reliable for E, Z; do not perform for group 4 drugs
-Perform HIV test. If positive, initiate CPT immediately and ART to all TB
patients within the first 8 weeks after initiation of anti-TB treatment
At least 4 effective drugs never used in the past and/or susceptible by
DST, taking into account DST reliability and cross-resistance
Use Z and evaluate the use of E, but neither should be considered as
one of the 4 main effective drugs. E should be considered especially in
patients just receiving before the Category I regimen.
Include just one Group 2 drug: one newer generation Fq, preferably
high dose Lfx (1 gr), or Mox
Include one Group 3 drug: One SLD injectable (Km, Ak, or Cm)
Include as many as needed of Group 4 drugs (Eth/Pth, Cs/Tz, PAS)
until to have, at least, 4 effective drugs in the regimen. Always
consider Eth/Pth as the first choice among Group 4 drugs.
If necessary, use Group 5 drugs to strengthen the regimen or when a 4
effective drug regimen has not been reached with the previous groups.
If available, Lz should be the first choice among Group 5 drugs.
Minimum length of treatment is 20 months, divided as follows:
IP: 6 months and at least 4 months after culture conversion. Longer if
3 effective drugs are not available during the continuation phase or if
the drugs are from group 5
CP: Minimum of 14 months
Consider only if few effective drugs are available, localised pulmonary
lesions are present and the person has sufficient respiratory reserve
Standardised: if there has been no use of SLDs in the past
Individualised: if there has been use of SLDs in the past or contact
with an MDR patient who had used them (Treat with the effective
regimen of the index case).A case of XDR-TB must always receive a
Individualized regimen.

Ak: amikacin; Am/Cl: amoxicillin/Clavulanic acid; ART: anti-retroviral therapy;Cm: capreomycin; Clo:
clofazamine; CP: Continuation Phase; CPT: cotrimoxazole preventive therapy; Cs: cycloserine; DST: drug
susceptibility test;Gat: gatifloxacin; MDR-TB: Multi-Drug Resistant Tuberculosis; E: Ethambutol; Et:
ethionamide; Eth/Pth: Ethionamide/Prothionamide; FLDs: first line drugs; Fq: fluoroquinolones; H:
isoniazid; IP: Intensive Phase;Km: kanamycin; Lfx: Levofloxacin; Mox: moxifloxacin; Of: ofloxacin; PAS:
para-amino salicyclic acid; R: rifampicin;SLDs: second line drugs; SLDI: Second Line Drug Injectables; Tz:
Terizidone; Lz: Linezlid; XDR-TB:Extensively-Drug Resistant Tuberculosis;Z: pyrazinamide;

Based in:
1.Caminero JA. Treatment of multidrug-resistant tuberculosis: evidence and controversies.
Int J Tuberc Lung Dis 2006;10:829-37.
2.Caminero JA, ed. Guidelines for Clinical and Operational Management of DrugResistant Tuberculosis. Paris, France: International Union Against Tuberculosis
and Lung Disease, 2013

Rational Classification of Anti-TB Drugs to Build

an MDR/XDR Regimen of at Least 4 Effective Drugs

Drugs

How used

Group 1:

First Line Drugs

Oral drugs:
H, R, E, Z

Group 2:
Fluoroquinolones Of,
Lf, Mox, Gat.

Group 3: Second Line

Injectables: Km, Ak,
Cap.

Use Z and evaluate the use of E (depending on the medication

history), but neither should be considered as one of the 4 main
effective drugs.
E should be considered especially in patients just receiving
before the Category I regimen
Include just one drug of this group
Preferably high dose Lfx (1 gr), or Mox
It must always be included in a regimen for MDR/XDR-TB
It must be considered as one of the 4 main effective drugs in
MDR-TB.
It must NOT be considered as one of the 4 main effective
drugs in XDR-TB.

Group 4:

Other Second Line

Drugs: Eth/Pth, Cs/Tz,
PAS

Group5:
Reinforcement Drugs:
Lz, Clof.,
Carbapenems, Am/Cl

Include just one drug of this group.

It must always be included in a regimen for MDR/XDR-TB
It must be considered as one of the 4 main effective drugs
in MDR-TB.
It must NOT be considered as one of the 4 main effective
drugs in XDR-TB
Add as many as needed to complete an effective 4 drug
regimen
Always prefer Eth/Pth, if considered effective, and then
Cs/Tz, and finally PAS.

Only use if not able to complete an effective 4 drug

regimen using drugs from Group 1, 2, 3 and 4.
If available, Lz should be the first choice among Group
5 drugs, followed by Clof.
High doses of INH must not be included in this group.
Bedaquiline (compassionate drug) also could be
considered in this group

Based in:
1.World Health Organization. Guidelines for the programmatic management of drugresistant tuberculosis. Emergency update 2008. World Health Organization Document
2008;WHO/HTM/TB/2008.402:1-247.

2. Caminero JA, Sotgiu G, Zumla A, Migliori GB. Best drug treatment for multidrugresistant and extensively drug-resistant tuberculosis. Lancet Infect Dis 2010;10:621-9.