GLOSSARY

• INTRODUCTION

• RISK FACTOR

• DEFINITION

• INVESTIGATIONS

• TREATMENT

• NOTIFICATION AND REGISTRATION

• DOTS

• MONITORING

• SURVEILLANCE POST TREATMENT

• LTBI TREATMENT IN CLOSE CONTACT PERSONS

• CONCLUSION
 AS WITH OTHER FORMS OF DRUG
RESISTANCE, THE PHENOMENON OF MDR
TUBERCULOSIS IS ENTIRELY MAN-MADE
 DRUG RESISTANT BACILLI ARE THE CONSEQUENCE OF HUMAN
ERROR IN ANY OF THE FOLLOWING

Prescription of chemotherapy
Management of drug supply
Case management
Process of drug delivery to the patient
Patient factor
 THE MOST COMMON MEDICAL ERRORS LEADING TO THE
SELECTION OF RESISTANT BACILLI ARE THE FOLLOWING:

• The prescription of inadequate chemotherapy to the multibacillary pulmonary tuberculosis

cases (e.g. Only 2 or 3 drugs during the initial phase of treatment in a new smear-positive
patient with bacilli initially resistant to isoniazid)
• The addition of one extra drug in the case of failure, and repeating the addition of a
further drug when the patient relapses after what amounts to monotherapy.
 THE MOST COMMON ERRORS OBSERVED IN THE MANAGEMENT
OF DRUG SUPPLY ARE THE FOLLOWING

The difficulty experienced by poor patients in obtaining all the drugs that they need (due
to lack of financial resources or social insurance)
Frequent or prolonged shortages of antituberculosis drugs (due to poor management
and/or financial constraints in developing countries)
Use of drugs (or drug combinations) of unproven bioavailability
 THE FOLLOWING ALSO HAVE THE EFFECT OF MULTIPLYING THE RISK OF
SUCCESSIVE MONOTHERAPIES AND SELECTION OF RESISTANT BACILLI

The patient's lack of knowledge (due to a lack of information or due to inadequate

explanation before starting treatment)
Poor case-management (when the treatment is not directly observed, especially during the
initial phase)
Adverse drug reaction
 If there is no response to the standard WHO retreatment regimen, remember that many apparent
treatment failures are due to the patient having failed to take his treatment and not due to MDR
bacilli.
 Explain to the patient how essential it is to know exact details of his previous treatment.
 Must know the prescribed treatment the patient actually took.
 The patient may not be able to admit that failure is the patient’s own fault, so also question the family
in the same way, and in the patient’s absence.
 Check patient’s previous records and pharmacist’s dispensing.

IMPORTANCE OF COUNSELLING
CLINICAL FACTORS PROMOTING RESISTANCE

 Inappropriate drug regimen

 Inadequate initial therapy
 Incomplete course of treatment
 Inappropriate treatment modification
 Adding single drug to a failing regime
 Inappropriate use of chemoprophylaxis
 Poor adherence and incomplete follow up
 Failure to isolate MDR-TB patients
 Failure to employ DOT
 Over the counter anti TB
WHEN TO SUSPECT DR-TB

 Re-treatment patient who’s sputum smear remains positive at 3 months of intensive phase
 Treatment failure and interruption cases
 Close contacts of MDR-TB cases
 Positive diagnosis with TB culture and DST
BASIC PRINCIPLES FOR MANAGEMENT OF MDR TUBERCULOSIS

 DESIGNING AN APPROPRIATE REGIMEN

 RELIABLE SUSCEPTIBILITY TESTING

 RELIABLE DRUG SUPPLIES

Definition
Rifampicin-susceptible, isoniazid-resistant TB (Hr-TB): caused by M.
tuberculosis strains resistant to isoniazid and susceptible to rifampicin.

H R
resistance susceptible
Definition
• Rifampicin-resistant TB (RR-TB): TB caused by M. tuberculosis strains
resistant to rifampicin.
• These strains may be susceptible or resistant to isoniazid (i.e. MDR-
TB), or resistant to other first-line or second-line TB medicines.
• MDR-TB and RR-TB cases are often grouped together as MDR/RR-TB
and are eligible for treatment with MDR-TB regimens.

R resistant But, if H resistant MDR TB

RR-TB
Can also have resistant to Ethambuthol, Pyrazinamide Streptomycin and secondline except
Fluroquinolones, bedaquiline and linezolid
Definition

MDR-TB: TB caused by Mycobacterium Tuberculosis (M. tuberculosis)

strains that are resistant to at least both rifampicin and isoniazid.

R H
resistant resistant
Can also have resistant to Ethambuthol, Pyrazinamide,
Streptomycin and secondline except Fluroquinolones, bedaquiline
and linezolid
Definition
Extensively drug resistant TB (XDR-TB):
Pre-XDR-TB: TB caused by Mycobacterium tuberculosis (M. tuberculosis) strains that fulfil the definition of
MDR/RR-TB and that are also resistant to any fluoroquinolone
XDR-TB: TB caused by Mycobacterium tuberculosis (M. tuberculosis) strains that fulfil the definition of
MDR/RR-TB and that are also resistant to any fluoroquinolone and at least one additional Group A drug

HR Lfx /MFx Bdq/Lzd

resistant resistant resistant

PRE-XDR-TB

XDR-TB
 Investigations

FIRST LINE SUSCEPTIBILITY SECONDLINE SUSCEPTIBILITY

• Culture- solid & liquid
• Xpert Ultra
• First-line Lineprobe Assay
• Lateral flow urine lipoarabinomannan assay (LF-LAM)
• Loop-mediated isothermal amplification (TB-LAMP)
• Truenat MTB, MTB Plus
• Moderate complexity automated NAATs
• (Abbott RealTime MTB and Abbott RealTime MTB
RIF/INH (Abbott)
• Culture- solid & liquid
• Xpert Ultra
• Xpert MTB/XDR (low complexity automated NAATs)
• Second-line Lineprobe Assay
• Truenat MTB, MTB Plus, MTB-RIF Dx
• Moderate complexity automated NAATs
• (Abbott RealTime MTB and Abbott RealTime MTB
RIF/INH (Abbott)
• BD MAX™ MDR-TB (Becton Dickinson)
• cobas® MTB and cobas MTB-RIF/INH (Roche)
• FluoroType® MTBDR and FluoroType® MTB (Hain
Lifescience/Bruker)
• High complexity reverse hybridization based NAATs
• Genoscholar PZA-TBII (Nipro)
Treatment of Hr-TB and
RR/MDR-TB
 ISONIAZID-RESISTANT TB

 In patients with confirmed rifampicin-susceptible, isoniazid-resistant tuberculosis (Hr-TB), treatment with

rifampicin, ethambutol, pyrazinamide and levofloxacin is recommended for a duration of 6 months

 Levofloxacin is proposed as the fluoroquinolone of first choice in the Hr-TB treatment regimen
 Safety profile of this medicine is better characterized than that of other fluoroquinolones
 The fluoroquinolone most frequently used in the studies reviewed for this guidance.
 Levofloxacin has fewer known drug interactions with other medications.
 Both plasma peak concentration and exposure to moxifloxacin decrease significantly when the drug is combined with
rifampicin
 levofloxacin undergoes limited metabolism in humans and is excreted unchanged in the urine
 There are no contraindications for levofloxacin use with other antiretroviral agents
 THE ADDITION OF LEVOFLOXACIN TO (H)REZ IS RECOMMENDED IN
PATIENTS WITH HR-TB, WITH THE EXCEPTION OF THE FOLLOWING
SITUATIONS

 Resistance to rifampicin cannot be excluded (i.E. Unknown susceptibility to rifampicin, or

indeterminate or error results on xpert MTB/RIF)
 Known or suspected resistance to levofloxacin
 Known intolerance to fluoroquinolones
 Known or suspected risk for prolonged QT interval
 If possible, in pregnancy or during breastfeeding (not an absolute contraindication)

If levofloxacin cannot be used because of toxicity or resistance, the patient may be given 6(H)REZ
as an alternative.
Based on the results of the evidence review for these guidelines, replacement of levofloxacin with
an injectable agent is NOT advised.
 BENEFIT OF ADDING LEVOFLOXACIN

 Treatment success rates were higher (aor: 2.8; 95% cl: 1.1–7.3)
 The number of deaths was reduced (aor: 0.4; 95% cl: 0.2–1.1)
 Acquisition of additional resistance with progression to MDR-TB was also reduced (aor: 0.10; 95% cl: 0.01–1.2),
 Acquired resistance to rifampicin 0.5% (1/221) of patients on ≥6(H)REZ plus fluoroquinolones compared with
3.8% (44/1160) of patients who did not receive fluoroquinolones
When additional resistance (e.g. to both fluoroquinolones and pyrazinamide) is
suspected or confirmed, treatment regimens that include other second-line TB
medicines may have to be designed individually.
 Sometimes, the confirmation of isoniazid resistance arrives late (e.g. 5 months into a 2HREZ/4HR regimen).

 In such cases, a decision to start 6 months of (H)REZ–levofloxacin depends on the patient’s clinical condition and
microbiological status.
Case scenario

• Hr-TB and rifampicin susceptibility are confirmed before TB treatment

is started. Treatment with (H) REZ–levofloxacin is started immediately.
• If the diagnosis is strongly presumed (e.g. close contacts of a
confirmed Hr-TB source case) but results of DST are still pending, the
regimen may be introduced.
• Should the DST results taken at the start eventually show
susceptibility to isoniazid, then levofloxacin is stopped, and the
patient continues treatment in order to complete a 2HREZ/4HR
regimen
Case scenario
• Hr-TB is confirmed after the start of treatment with the 2HREZ/4HR regimen.
• This includes patients who had undiagnosed isoniazid resistance at the start or
who developed isoniazid resistance later while on treatment with a first-line
regimen.
• Rapid molecular testing for rifampicin resistance must be done (or repeated).
• Once rifampicin resistance has been excluded, a full 6-month course of (h)rez–
levofloxacin is given.
• The duration is driven by the need to give levofloxacin for 6 months, which
usually implies that the companion first-line medicines are taken for longer than
this.
• If rifampicin resistance is detected, the patient needs to be started on a
recommended MDR-TB treatment regimen
RR/MDR-TB
SHORTER RR/MDR-TB REGIMEN
 SHORTER ALL-ORAL BEDAQUILINE-CONTAINING REGIMEN

Intensive phase • Bedaquiline (6 months)

 A shorter all-oral bedaquiline-containing regimen of (4-6 months) • Levofloxacin/moxifloxacin
9–12 months duration is recommended in: -Extending to 6 months if the • Ethionamide
patient remains sputum • Ethambutol
 Eligible patients with confirmed multidrug- or
rifampicin-resistant tuberculosis (MDR/RR-TB) smear positive at the end of • Isoniazid (high-dose)
4 months • Pyrazinamide
 Not been exposed to treatment with secondline TB • Clofazimine
medicines used in this regimen for more than
1 month

 Resistance to fluoroquinolones has been excluded.

 The evidence reviewed supports the use of this Maintenance phase • Levofloxacin/moxifloxacin
regimen in patient subgroups such as people living (5 months) • Clofazimine
with HIV (PLHIV) • Ethambutol
 Implementation of this regimen requires access to
• Pyrazinamide
rapid DST against fluoroquinolones.
 Shorter All-oral Bedaquiline-containing Regimen

CURE RATE

 Relapse-free cure in about 80% of cases or more if used in carefully selected MDR/RR-TB patients who have not
been previously exposed or do not have additional resistance to second-line medicines
 SHORTER ALL-ORAL BEDAQUILINE-CONTAINING REGIMEN

 A total of 10 152 records of patients with MDR/RR-TB initiating TB treatment anytime between January and June 201727 were
considered, of which the following were included for primary28 analyses: 891 patients who received a shorter all-oral bedaquiline-
containing regimen (intervention), 987 patients treated with a shorter regimen that included an injectable agent, 1437 patients treated
with longer (2016) regimens, and 474 treated with longer regimens that included at least bedaquiline.
 The primary analysis comparing South African programmatic data indicated that the use of a shorter all-oral bedaquiline-containing
regimen in patients with MDR/RR-TB was associated with higher treatment success rates (73% all-oral versus 60% standardized shorter
regimen success rates, aOR for success versus failure/recurrence: 2.1, 95% confidence interval [CI]: 1.1–4.0; aOR success versus death: 1.6,
95% CI: 1.2–2.1; aOR success versus failure/recurrence/death: 1.7, 95% CI: 1.3–2.2; and aOR success versus all unfavourable outcomes: 1.9,
95% CI: 1.6–2.4); and lower loss to follow-up than a standardized shorter regimen in which an injectable agent was used (aOR loss to
follow-up versus all other outcomes: 0.5, 95% CI: 0.4–0.7). A similar effect for subgroups of patients with acidfast bacilli (AFB) smear-
positive sputum and HIV-positive and negative patients was observed with the use of the shorter all-oral bedaquiline-containing regimen.
The analysis also suggested that when the shorter all-oral bedaquiline-containing regimen was compared to an injectable-free longer29
regimen containing bedaquiline, there seemed to be no marked differences in the outcomes observed. However, relatively modest
beneficial effects were noted in the direction of the intervention; in particular, success versus failure/recurrence (aOR: 3.9; 95% CI: 1.7–
9.1), success versus all unfavourable outcomes (aOR: 1.6; 95% CI: 1.2–2.2) and loss to follow-up (aOR: 0.5; 95% CI: 0.4–0.8), all favouring
the use of the all-oral shorter regimen. Further subgroup analysis seemed to indicate that there were consistent differences in treatment
outcomes, as observed in primary analyses among subgroups, in particular among AFB smear-positive patients and in HIV-positive
individuals on ART; however, differences in treatment outcomes in all-oral shorter and longer regimens were no longer significant when
looking at outcomes for HIV-negative individuals, with the exception of loss to follow-up, which favoured the intervention.The additional
comparison also illustrated the effect of a shorter all-oral bedaquiline-containing regimen in comparison to longer regimens without any
new drugs. The all-oral shorter regimen performed significantly better across all outcomes and all subgroups in this comparison.
 SHORTER ALL-ORAL BEDAQUILINE-CONTAINING REGIMEN

 Usage of Linezolid

 During the development of the WHO module, only 0.5% of patients received linezolid, and no treatment outcomes were
available for these patients. Hence, all patients who received linezolid were excluded
SECOND LINE ANTI-TB
Group name Name of the drugs Abbreviation
A. Fluoroquinolones1 Levofloxacin Lfx
Moxifloxacin Mfx
Gatifloxacin Gfx
B. Second-line injectable Amikacin Am
agents Capreomycin Cm
Kanamycin Km
(Streptomycin)2 (S)
C. Other core second- Ethionamide / Prothionamide Eto / Pto
line agents1 Cycloserine / Terizidone Cs / Trd
Linezolid Lzd
Clofazimine Cfz
D. Add-on agents Pyrazinamide Z
(not part of the core D1 Ethambutol E
MDR-TB regimen) High-dose isoniazid Hh
Bedaquiline Bdq
D2
Delamanid Dlm
p-aminosalicylic acid PAS
Imipenem-cilastatin3 Ipm
D3 Meropenem3 Mpm
Amoxicillin-clavulanate3 Amx-Clv
WHO 2011
(Thioacetazone)4 (T)
CONVENTIONAL TREATMENT REGIMENS FOR RIFAMPICIN-
RESISTANT TB

Recommendations

a) In patients with rifampicin-resistant or multidrug-resistant TB, a regimen with at least FIVE EFFECTIVE TB
MEDICINES during the intensive phase is recommended, including PYRAZINAMIDE AND FOUR CORE
SECOND-LINE TB medicines

b) In patients with rifampicin-resistant or multidrug-resistant TB, it is recommended that the regimen be further
strengthened with high-dose isoniazid and/or ethambutol (conditional recommendation, very low certainty in the
evidence).
 STANDARD MDR-TB REGIMEN

 Consist of 4 second-line antiTB drugs that are most likely to be effective in the intensive phase

Injectables Aminoglycoside

Fluoroquinolones

Cycloserine and Clofazimine

+/-Ethionamide

Pyrazinamide

*In the treatment of patients with MDR-TB, a later-generation fluoroquinolone

rather than an earlier-generation fluoroquinolone should be used
 DURATION OF TREATMENT
 INTENSIVE PHASE
 Defined by the duration of treatment with the injectable agent
WHO recommends 8 months for most patients

 DURATION OF TREATMENT
 Newly MDR-TB (i.e. not previously treated for MDR-TB), a total treatment
duration is 20 months for most patients

May be modified according to the response to treatment based on

patient’s cultures, smears, CXR & clinical status
GROUPING OF MEDICINES RECOMMENDED FOR USE IN LONGER
MDR-TB REGIMENS

Group C
Group A Group B (Add to complete and when
(Include all 3 medicines) (Add one or both Medicine) medicines from Group A and B
cannot be used)
Fluoroquinolones Ethambutol
(Levofloxacin And
Moxifloxacin) Clofazimine Delamanide
Pyrazinamide
Bedaquiline Imipenem/Meropenem
Amikacin/Streptomycin
Cycloserine Or Terizidone Ethionamide
Linezolid
PAS
 ORAL LONGER REGIMENS FOR MULTIDRUG- OR RIFAMPICIN-
RESISTANT TUBERCULOSIS

 All three group A agents and at least one group B agent should be included to ensure that treatment starts
with at least four TB agents likely to be effective, and that at least three agents are included for the rest of
treatment if bedaquiline is stopped.

 If only one or two group a agents are used, both group B agents are to be included. If the regimen cannot be
composed with agents from groups A and B alone, group C agents are added to complete it.
 NUMBER OF AGENTS LIKELY TO BE EFFECTIVE

▪ In multidrug- or rifampicin-resistant tuberculosis (MDR/RR-TB) patients on longer regimens,

▪ All three group A agents and
▪ At least one group B agent should be included to ensure that treatment starts with
▪ At least four TB agents likely to be effective,
▪ At least three agents are included for the rest of treatment if bedaquiline is stopped

▪ Given that drug–drug interactions, pill burden and likelihood of adverse events all increase with the number of
agents in a regimen

▪ Minimum number of medicines necessary to obtain comparable levels of relapse-free cure.

▪ The risk of treatment failure, relapse and death was comparable when the treatment started with four, five or six
medicines likely to be effective.
 For patients in whom two agents from group A are more likely to be stopped

before the end of treatment, then starting with five effective agents rather than four

may be advisable.
SERIOUS ADVERSE
EVENT IN PATIENTS
ON LONGER MDR-
TB REGIME
 IN MDR/RR-TB PATIENTS ON ORAL LONGER
REGIMENS

A total treatment duration of 18–20 months is suggested for most patients;

the duration may be modified according to the patient’s response to therapy.

A treatment duration of 15–17 months after culture conversion is suggested

for most patients; the duration may be modified according to the patient’s
response to therapy.

Longer regimens containing amikacin or streptomycin, an intensive phase of

6–7 months is suggested for most patients; the duration may be modified
according to the patient’s response to therapy.
 IN MDR/RR-TB PATIENTS ON ORAL LONGER
REGIMENS

Kanamycin and capreomycin are not to be included in the treatment of MDR/RR-TB patients on longer
regimens

Amikacin may be included in the treatment of MDR/RR-TB patients aged 18 years or more on longer
regimens when susceptibility has been demonstrated and adequate measures to monitor for adverse
reactions can be ensured. If amikacin is not available, streptomycin may replace amikacin under the
same conditions.

Bedaquiline should be included in longer multidrug-resistant TB (MDR-TB) regimens for patients aged
18 years or more and may also be included in longer MDR-TB regimens for patients aged 6–17 years.
 IN MDR/RR-TB PATIENTS ON LONGER REGIMENS

Clavulanic acid should

not be included in the
treatment of MDR/RR-
TB patients on longer
Ethionamide or regimens.
P-aminosalicylic acid
prothionamide may be This medicine should be
may be included only if Imipenem–cilastatin or
included only if included in mdr/rr-tb
bedaquiline, linezolid, meropenem may be
bedaquiline, linezolid, regimens only as a
clofazimine or delamanid included in the
clofazimine or delamanid companion agent to the
are not used, or if better treatment of MDR/ RR-
are not used, or if better carbapenems
options to compose a TB patients on longer
options to compose a
regimen are not regimens. It should be given with
regimen are not
possible. every dose of
possible.
carbapenem
Should not be counted
as an additional effective
TB agent
 TREATMENT OF XDR-TB

• Success in XDR-TB patients was highest if at least six drugs were used in the intensive phase and four
in the continuation phase.

• The use of later-generation fluoroquinolone significantly improved treatment outcomes in patients

with XDR-TB, even though DST demonstrated resistance to a representative fluoroquinolone

• The BPaL regimen for multidrug-resistant tuberculosis with additional fluoroquinolone resistance.

• A treatment regimen lasting 6–9 months, composed of bedaquiline, pretomanid and linezolid (BPaL),
may be used under operational research conditions
NOTIFICATION AND REGISTRATION

DRTBIS 50 series
 DOT
• DOT means that a trained health care worker or other designated
individual provides the prescribed TB drugs and watches the patient
swallow every dose

• DOT includes: delivering the prescribed medication

– Checking for side effects
– Watching the patient swallow the medication
– Documenting the visit
– Answering questions
 Community- or Home-based DOT vs
Health Facility-based DOT
• RCTs and observational studies examined how DOT location affected treatment outcome.
• Locations were grouped by community- or home-based DOT, and health facility-based DOT
• Community- or home-based DOT was defined as DOT delivered in the community close to the patient’s home or workplace.
• Community or home-based DOT vs Health-facility-based DOT
• Close to the patients
• Higher rates of treatment success, cure, treatment completion and 2-month sputum conversion
• Lower rates of mortality and lower rates of unfavorable outcomes
• Community-/home-based DOT compared with SAT.
• Higher rates of treatment success and adherence, and a lower rate of loss to follow-up
• Health-facility DOT compared to SAT
• Lower rates of treatment completion, and slightly higher rates of failure and loss to follow-up in.
• Community- or home-based DOT is the preferred option rather than health facility-based DOT and SAT.
• DOT delivered at a health facility, DOT provided by a family member and unsupervised treatment are not preferred options
 Video-observed Treatment (VOT)
• The advantages of using VOT are:
• Its potential to observe adherence to treatment from a distance – and even when
people travel and cannot visit or be visited by a DOT provider.
• More flexible to people’s schedules by offering virtual observation at different times of
the day.
• Achieve better levels of patient interaction at a much lower cost and less inconvenience
when compared with in-person DOT.
 MONITORING
Intensive Phase Maintenance Phase

Visits Monthly 1-3Monthly

Weight Monthly 1-3Monthly
Sputum AFB Monthly 1-3Monthly
Mycobacterium C+S Monthly 1-3Monthly
ECG Monthly PRN
RP/LFT Monthly PRN
TFT (ethionamide) 3 -6 Monthly 3-6 Monthly
CXR 6 Monthly 6 Monthly
Adverse Effects Monthly 1-3Monthly
Surveillance Post Treatment

• Assess patient for history and physical examination.

• Checks sputum culture six monthly for two years after completion
date to evaluate for possible recurrence
 Contacts Of Multidrug-resistant Tuberculosis Patients
▪ In selected high-risk household contacts of patients with multidrug-resistant tuberculosis, preventive
treatment may be considered based on individualized risk assessment and a sound clinical judgement.
▪ Treatment should be given to selected individuals after a careful risk assessment
▪ Intensity of exposure
▪ Certainty of the source of disease
▪ Reliable information on the drug resistance pattern of the source
▪ Potential adverse drug reactions
▪ It should be given only to household contacts at high risk (e.g. children, people on immunosuppressive
therapy, PLHIV)
▪ May also apply to HIV-negative individuals.
▪ Confirmation of infection by LTBI testing is required before treatment is initiated
▪ Contacts of people with rifampicin-resistant TB (RR-TB) are usually treated as for MDR-TB unless isoniazid-
susceptibility in the index case is reliably confirmed, in which case IPT may be effective.
Conclusion of Hr-TB

Dignosis Hr- Sputum

negative 6REZLfx
TB confirmed Xpert Ultra

Postive

MDR-TB
RR/MDR-TB – Oral longer regimen
Group A
(Include all 3 medicines)
Levofloxacin / Moxifloxacin Bedaquiline Linezolid

MINIMUM 4 DRUGS
Group B
(Add one or both Medicine)
Clofazimine Cycloserine

Group C
(Add to complete and when medicines from Group A and B cannot be used)
Imipenem/ Amikacin/
Ethambutol Delamanide Pyrazinamide Ethionamide PAS
Meropenem Streptomycin
RR/MDR-TB – Oral shorter regimen

Intensive phase • Injectable agent was replaced by bedaquiline

(4-6 months) (used for 6 months)
-Extending to 6 months if the patient remains sputum • Levofloxacin/moxifloxacin
smear positive at the end of 4 months • Ethionamide
• Ethambutol
• Isoniazid (high-dose)
• Pyrazinamide
• Clofazimine
Maintenance phase • Levofloxacin/moxifloxacin
(5 months) • Clofazimine
• Ethambutol
• Pyrazinamide
Conventional treatment regimens for
rifampicin-resistant TB
Recommendations

a) In patients with rifampicin-resistant or multidrug-resistant TB, a regimen

with at least FIVE EFFECTIVE TB MEDICINES during the intensive phase is
recommended, including PYRAZINAMIDE AND FOUR CORE SECOND-LINE
TB medicines

b) In patients with rifampicin-resistant or multidrug-resistant TB, it is

recommended that the regimen be further strengthened with high-dose
isoniazid and/or ethambutol (conditional recommendation, very low
certainty in the evidence).