MULTIDRUG-

RESISTANT
TUBERCULOSIS
(MDR-TB)

by
Dr Mat Zuki Mat Jaeb

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 LEARNING OBJECTIVES

To identify those at risk of MDR-TB

To learn on what to do when MDR-TB is

suspected

To learn the basic principles of treatment

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 MULTIDRUG- RESISTANT
TUBERCULOSIS (MDR-TB)
Outline
Introduction
Definition
Risk Factors
Diagnosis
Principle of Management
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 INTRODUCTION
MDR & Extensively drug-resistant TB (XDR-TB)
incidence & prevalence are increasing worldwide
including Malaysia
Rate of MDR-TB cultures had increased from 0.3% in 2005
to 1.3% in 2011 of all MTB cultures positive in Malaysia1

High mortality & morbidity

In a study in Vietnam, mortality during MDR-TB treatment
was 8.7%2

1Sistem Maklumat Tibi KKM, 2011

2Quy HT et al., Int J Tuberc Lung Dis, 2006

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 INTRODUCTION

Complex treatment, costly & long

treatment duration

Drugs adverse effects - compliance

issues

Importance of strict infection control

measures
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MDR-TB WORLDWIDE IN 2011 -
ABSOLUTE NUMBER OF CASES

http://www.who.int/topics/tuberculosis/en/
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MDR-TB TREATMENT OUTCOME
IN WESTERN PACIFIC REGION

http://www.who.int/topics/tuberculosis/en/
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 DEFINITION

Monodrug resistant
 MTB resistant to any one of antiTB drugs

Polydrug resistant
 MTB resistant to 2 or more antiTB drugs

Multidrug resistant
 MTB resistant to both isoniazid & rifampicin with
or without resistance to other antiTB drugs
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 DEFINITION

Extensively drug-resistance (XDR)

 MDR TB with resistance to at least one injectable
second-line antiTB drugs & any fluoroquinolone

Extremely/Total drug-resistant TB
not well-defined
MTB resistant to all tested first-line & second-line
antiTB drugs

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 TYPE OF MDR-TB

Primary drug resistance

Patient has never received antiTB drug

 Secondary/acquired drug resistance

Patient has received antiTB drug

Inadequate treatment or improper use of the

antiTB medications remains an important cause
of drug-resistant TB

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 RISK FACTORS
 Previously treated TB patient
● Relapse
● Treatment failure
● Treatment after interruption (TAI)
are at higher risk of having secondary MDR-TB with
OR of 9.1 & 10.2.1,2

1Conaty SJ et al., Epidemiol Infect, 2004

2Faustini A et al., Thorax, 2006

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 RISK FACTORS
Independent risk factors for MDR-TB among
previously treated patients:1
i. Smear-positive disease (OR=5.8)
ii. New immigrants from a country with high MDR-
TB prevalence (OR=6.9)
iii. Frequent traveller to a country with high MDR-TB
prevalence (OR=2.5)
iv. Younger age group (OR=0.95)
1Law WS et al., Int J Tuberc Lung Dis, 2008

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 RISK FACTORS

 HIV-positive patients have more than

twice risk of primary MDR-TB.1
1Suchindran S et al., PLoS ONE, 2009

Clinical specimen from all TB cases must have

Mycobacterium tuberculosis culture & sensitivity test
done at diagnosis & repeated whenever drug
resistance is suspected.
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 DIAGNOSIS
MDR- & XDR-TB is a laboratory diagnosis

Culture & DST for Mycobacterium tuberculosis

LJ Media
Automated/liquid media

Nucleic Acid Testing (NAAT)

 Line Probe Assay - detects resistance to isoniazid &
rifampicin
 Gene expert system (Xpert MTB/RIF) - detects MTB
resistance to rifampicin (surrogate marker for MDR)

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 PRINCIPLES OF TREATMENT
 Rapid diagnosis & prompt treatment

 MDR-TB patients should be referred to physician

with experience in management of MDR TB

 Empirical MDR-TB regimen may be commenced for

patients who are highly likely to have MDR-TB while
waiting for laboratory confirmation

 Infection control measures - strict isolation of smear

positive MDR-TB patients

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 MDR-TB TREATMENT REGIMEN

1. Standard MDR-TB regimen (standardised

approach)

or

2. Individually-tailored regimen
- regimen will be based on DST for second-line
drugs

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SECOND-LINE ANTITB DRUGS

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 STANDARD MDR-TB REGIMEN

Consist of 4 second-line antiTB drugs that are most

likely to be effective in the intensive phase

Regimens should include:

Second- ● Fluoroquinolone
line
● Parenteral agent (aminoglycosides)
antiTB
drugs ● Ethionamide &
● Either cycloserine or PAS (if cycloserine
cannot be used) &
● Pyrazinamide
later-generation fluoroquinolone (e.g. levofloxacin
& moxifloxacin) should be used
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 STANDARD MDR-TB REGIMEN

Ethambutol & Group 5 drugs may be

used but is not included among the
drugs making up the standard regimen.

 Each drug in an MDR-TB regimen is

given as DOT throughout the treatment.

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 MONITORING
 Monthly sputum smears & cultures until smear &
culture conversion occur
 “Conversion”- 2 consecutive negative smears & cultures
taken 30 days apart

 After conversion, smears are monitored monthly &

cultures 3-monthly

 Monthly monitoring by clinician until sputum

conversion, then every 2 - 3 monthly

 At each visit, patient’s weight & side effects to

antiTB drugs should be monitored
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 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
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 CASE
YCL, 50 y.o., F
• Newly diagnosed DM on OHA
• PTB sp AFB +ve on 5/11/2009 & treated at KK
• Initially she responded to SHRZ & HR biweekly but
with minimal weight gain (49 - 51kg)
• July 2010 noted smear positive again, continue H3R3
• Restarted EHRZ in November 2010 (smear 50/L),
weight 45 kg- awaiting MTB C&S, referred to RC
• Treatment failure
• MTB C&S revealed resistance to R & H
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 CASE (cont.)
• Started on KECOZ, on 25/1/2011
• April 2011 - complained of tinnitus, headache,
reduced hearing - mild ototoxicity
• Kanamycin stopped after referred to ENT surgeon
• Could not tolerate PZA due to arthritis - under
rheumatology
• Continue CEOC
• May 2011 - weight increased to 47 kg from 44 kg,
smear negative

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 CASE (cont.)
• September 2011 - nausea, vomiting, numbness &
poor appetite, weight reduced to 42 kg,
hypoglycaemia - admitted to ward for dehydration
CEOC was withheld few days then
continued….
• Oct 2011, Dec 2011, Jan 2012, Feb 2012 - tolerating
CEOC but not much improvement of appetite &
weight with on/off cough
• March 2012 - weight 39 kg, symptomatic, smear
positive
Persistent smear positive….. Story continues…..
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 TAKE HOME MESSAGES
MDR-TB must be suspected & investigated promptly
in previously treated TB patient & high risk groups

 Rapid test to diagnose MDR-TB should be carried

out on MDR-TB suspect

 MDR-TB should be treated by physician with

experience in managing MDR

Strict infection control measures should be practiced

to prevent MDR-TB transmission
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 THANK YOU

mzek4708@yahoo.com

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