Transcript CPG on TB: Prevention

MULTIDRUGRESISTANT
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 MDRTB 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:
Secondline
antiTB
drugs
●
●
●
●
●
Fluoroquinolone
Parenteral agent (aminoglycosides)
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
[email protected]
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