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MDR TB
HARIKRISHNAN. M
2010 MBBS
DEFINITION

MDR TB: TB caused by a
strain of M. tuberculosis
that is resistant to both
isoniazid and
rifampicin.
Why INH and Rifampin
 Most potent and bactericidal.
 Mono-resistance to one of them can be treated

effectively with a regimen containing the other agent
with very low failure rate (2.5-5%)
 Failure rate when INH + Rifampicin resistant is 44%
in non-HIV and 70% in HIV patients
 Duration required for cure doubles to triples.
EPIDEMIOLOGY
STATISTICS -INDIA
Estimates of MDR-TB
burden 2012

New

Retreatment

% of TB cases with MDRTB

2.2(1.9-2.6)

15(11-19)

MDR –TB cases among notified pulmonary
21000(18000-25000) 43000 (32000-54000) TB
cases
Reported cases of MDR TB 2012

Total

Cases tested for MDR TB

55611

Laboratory confirmed MDR TB cases

16588

Patients started on MDR TB treatment

14143
MDR SUSPECT
 Category I failures
 Category II patients who are smear positive at 4

months or later.
 Contacts of MDR cases who are found to be smear
positive.(2009)
DIAGNOSIS
 MDR-TB is not clinically distinguishable from drug-

susceptible TB at the outset.
 Signs, symptoms, and radiological findings are
similar initially to drug-susceptible TB.
 Sputum culture


DST(Drug Susceptibility Testing) –
definitive diagnosis of drug
resistant TB.

 2 methods
 Phenotypic and Genotypic
 Phenotypic method- culturing of M. tuberculosis in

the presence of anti TB drugs to detect growth
(indicating drug resistance) or inhibition of growth
(indicating drug susceptibility)
 Phenotype DST methods are performed as direct or
indirect tests on solid or liquid media.
 And among them Indirect

phenotype test is

extensively validated and are currently regarded as
GOLD STANDARD.
 Genotypic method- targets specific molecular

mutations associated with resistance against
individual drugs.
 Moleular testing allows rapid detection of resistance
to rifampicin( alone or in combination with
isoniazid). It provides DST results within one day.
 Catridge based nucleic acid amplification test(NAAT)
–very high sensitivity.
TREATMENT
 Difficult.
 WHO recommends DOTS PLUS guidelines initiated

by PMDT (Programmatic Management of Drug
Resistant TB)
 After diagnosis treatment of MDR TB is initiated at
designated DOTS Plus sites which are established in
tertiary care centres ( like medical colleges, large
speciality hospitals).
DOTS PLUS
Treatment regime :
6 (9) months - kanamycin
ofloxacin
ethionamide
cycloserine
pyrazinamide
ethambutol
18 months –Ofloxacin
Ethionamide
cycloserine
ethambutol
 Follow up:
 Smear examination should be conducted monthly

during intensive phase and atleast quarterly during
continuation phase.
 Culture examination should be done atleast at 4,6,12,
18 and 24 months of treatment.
 Treatment adherence : patient and family members

counselled prior to treatment initiation and during
follow up visits.
 Efforts should be made to administer treatment
under DOTS over entire period of treatment.
 Documentation of treatment : Systemic record of

treatment, regimen, doses, duration, side effects,
investigation results and treatment outcome for all
patients initiated on second line treatment should be
maintained.
2009 DOTS PLUS policy
 Defn of MDR suspect revised to include ‘contacts of

MDR cases who are found to be smear positive’
besides Cat I failures and Cat II patients who are
smear positive at 4 months or later.
 The existing exclusion criteria for MDR suspects i.e.
age <15 years and history of intake of 2nd line drugs
for more than 1 month in the past has been
withdrawn. A new weight band (16-25 kgs) has been
added for the treatment of pediatric MDR patients.
 Inorder to make the Cat IV regimen more effective it

has been decided to replace Ofloxacin with
Levofloxacin.
 Guidelines for management of MDR patients with
pregnancy has been finalised.
THANK YOU

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MDR TB

  • 2. DEFINITION MDR TB: TB caused by a strain of M. tuberculosis that is resistant to both isoniazid and rifampicin.
  • 3. Why INH and Rifampin  Most potent and bactericidal.  Mono-resistance to one of them can be treated effectively with a regimen containing the other agent with very low failure rate (2.5-5%)  Failure rate when INH + Rifampicin resistant is 44% in non-HIV and 70% in HIV patients  Duration required for cure doubles to triples.
  • 5. STATISTICS -INDIA Estimates of MDR-TB burden 2012 New Retreatment % of TB cases with MDRTB 2.2(1.9-2.6) 15(11-19) MDR –TB cases among notified pulmonary 21000(18000-25000) 43000 (32000-54000) TB cases
  • 6. Reported cases of MDR TB 2012 Total Cases tested for MDR TB 55611 Laboratory confirmed MDR TB cases 16588 Patients started on MDR TB treatment 14143
  • 7. MDR SUSPECT  Category I failures  Category II patients who are smear positive at 4 months or later.  Contacts of MDR cases who are found to be smear positive.(2009)
  • 8. DIAGNOSIS  MDR-TB is not clinically distinguishable from drug- susceptible TB at the outset.  Signs, symptoms, and radiological findings are similar initially to drug-susceptible TB.
  • 9.  Sputum culture  DST(Drug Susceptibility Testing) – definitive diagnosis of drug resistant TB.  2 methods  Phenotypic and Genotypic
  • 10.  Phenotypic method- culturing of M. tuberculosis in the presence of anti TB drugs to detect growth (indicating drug resistance) or inhibition of growth (indicating drug susceptibility)  Phenotype DST methods are performed as direct or indirect tests on solid or liquid media.
  • 11.  And among them Indirect phenotype test is extensively validated and are currently regarded as GOLD STANDARD.
  • 12.  Genotypic method- targets specific molecular mutations associated with resistance against individual drugs.  Moleular testing allows rapid detection of resistance to rifampicin( alone or in combination with isoniazid). It provides DST results within one day.  Catridge based nucleic acid amplification test(NAAT) –very high sensitivity.
  • 13. TREATMENT  Difficult.  WHO recommends DOTS PLUS guidelines initiated by PMDT (Programmatic Management of Drug Resistant TB)  After diagnosis treatment of MDR TB is initiated at designated DOTS Plus sites which are established in tertiary care centres ( like medical colleges, large speciality hospitals).
  • 14. DOTS PLUS Treatment regime : 6 (9) months - kanamycin ofloxacin ethionamide cycloserine pyrazinamide ethambutol
  • 16.  Follow up:  Smear examination should be conducted monthly during intensive phase and atleast quarterly during continuation phase.  Culture examination should be done atleast at 4,6,12, 18 and 24 months of treatment.
  • 17.  Treatment adherence : patient and family members counselled prior to treatment initiation and during follow up visits.  Efforts should be made to administer treatment under DOTS over entire period of treatment.
  • 18.  Documentation of treatment : Systemic record of treatment, regimen, doses, duration, side effects, investigation results and treatment outcome for all patients initiated on second line treatment should be maintained.
  • 19. 2009 DOTS PLUS policy  Defn of MDR suspect revised to include ‘contacts of MDR cases who are found to be smear positive’ besides Cat I failures and Cat II patients who are smear positive at 4 months or later.  The existing exclusion criteria for MDR suspects i.e. age <15 years and history of intake of 2nd line drugs for more than 1 month in the past has been withdrawn. A new weight band (16-25 kgs) has been added for the treatment of pediatric MDR patients.
  • 20.  Inorder to make the Cat IV regimen more effective it has been decided to replace Ofloxacin with Levofloxacin.  Guidelines for management of MDR patients with pregnancy has been finalised.