A brief view on MDR TB and XDR TB

1. SILAJIT DUTTA
B.Pharm.
3rd
Year, 6th
Semester
Guided by
Mr. RAJA CHAKRAVERTY
Asst. Professor
Bengal College of Pharmaceutical Sciences and Research

3. The bacteria that cause
tuberculosis (TB) can
develop resistance to
the antimicrobial drugs
used to cure the
disease. Multidrug-
resistant tuberculosis
(MDR-TB) is TB that
does not respond to at
least isoniazid and
rifampicin, the two most
powerful anti-TB drugs.
Definition of MDR TB & XDR TB
WHO - XDR-TB Task Force
Committee gave a much
accepted definition of XDR-TB
which defines it as "resistance
to at least rifampicin and
isoniazid among the first line-
anti tubercular drugs in
addition to resistance to any
fluroquinolones i.e. ofloxacin,
ciprofloxacin and levofloxacin,
and at least one of three
injectable second line anti
tubercular drugs i.e. amikacin,
kanamycin and capreomycin

4. Mechanism of Resistance
1. Conversion of wild type pan-susceptible strains to drug resistant strains
during treatment (acquired resistance)
2. Increasing development of resistance in drug-resistant strains because of
inappropriate chemotherapy (amplified resistance)
3. Transmission of drug-resistant cases (transmitted resistance)

5. Clinical factors promoting resistance
• Delayed diagnosis and isolationDelayed diagnosis and isolation
• Inappropriate drug regimen.Inappropriate drug regimen.
• Inadequate initial therapyInadequate initial therapy
• Incomplete course of treatmentIncomplete course of treatment
• Inappropriate treatment modificationsInappropriate treatment modifications
• Adding single drug to a failing regimenAdding single drug to a failing regimen
• Inappropriate use of chemoprophylaxisInappropriate use of chemoprophylaxis
• Poor adherence and incomplete F/UPoor adherence and incomplete F/U
• Failure to isolate MDR TB patientsFailure to isolate MDR TB patients
• Failure to employ DOTFailure to employ DOT
• Over the counter anti TBOver the counter anti TB
• Faked drugsFaked drugs

6. Bacteria coughed
out in sputum
Inhalation of bacteria
Bacteria reach lungs,
enter macrophages
Bacteria reproduce
in macrophages
Lesion begins to form
(caseous necrosis)
Activated
macrophages
Bacteria stop growing;
lesion calcifies
Immunosuppression
Reactivation
Lesion
liquefies
Dead
phagocytes,
necrosis
M. tuberculosis
Phagocytes,
T cells and
B cells
trying to
kill bacteria
DEATH
Spread to
blood/organs
Steps in the development of tuberculosis
6

8. TB TESTING:
1. XPERT Test
The Xpert MTB/RIF has been developed by the Foundation for Innovative New
Diagnostics (FIND), who have partnered with the Cepheid Corporation and the
University of Medicine and Dentistry of New Jersey.
The Xpert (GeneXpert) MTB/RIF test is a new molecular test for TB which
diagnoses TB by detecting the presence of TB bacteria, as well as testing for
resistance to the drug Rifampicin.
GeneXpert 4 module machine © GHE

9. Tuberculin skin test (20 mm in
diameter) was seen within 72 hours.
PPD Skin Test
Purified Protein Derivative
Standard
(PPD)
Mantoux Skin Test
2 mm2 mm
2. TB Skin Test2. TB Skin Test
Positive Tuberculin Skin Test

10. Categories of Antituberculosis Drugs: WHO
• Group 1 – First-line drugs: Isoniazid, rifampicin, ethambutol, pyrazinamide
• Group 2 - Injectable agents: Kanamycin, amikacin, capreomycin,
streptomycin
• Group 3 - Fluoroquinolones: Levofloxacin, moxifloxacin, ofloxacin
• Group 4 - Oral bacteriostatic agents: Ethionamide, cycloserine, para-
aminosalicylic acid (PAS), prothionamide, terizadone
• Group 5 – Unclear role: Clofazamine, linezolid, amoxicillin/clavulanate,
Imipenem/cilastatin, thioacetazone, high-dose isoniazid, clarithromycin,

11. TB drugs for children
In 2006 the World Health Organisation (WHO) first published specific guidance for national TB
control programs on the management of TB in children. This recommended that the first line
anti TB drugs that should be used for the treatment of TB in children should be:
•Isoniazid
•Rifampicin
•Pyrazinamide
•Ethambutol
and Streptomycin
Children with TB in South Africa ©WHO/TBP/Gary Hampton

12. Causes of inadequate TB treatment
Doctors - as a cause of inadequate TB treatment
Inappropriate guidelines
Noncompliance with guidelines
Absence of guidelines
Drugs - as a cause of inadequate TB treatment
Poor quality
Irregular supply
Wrong delivery (dose/combination)
Drugs are unsuitable due to drug resistance
Patients - as a cause of inadequate TB treatment
Lack of information
Lack of money for treatment and/or transport
Actual or presumed side effects
Lack of commitment to a long course of drugs
Malabsorption
Social barriers

13. Public health responsibilities of health care providers
􀂾 Health care facilities/practitioners managing confirmed MDR-TB patients should inform their
respective District TB Officer regarding treatment initiation and outcome of all MDR-TB cases
􀂾 prior to treatment initiation and on all follow up visits the patient and family members should
be counseled on all aspects of MDR-TB
􀂾 All house hold contacts of the MDR-TB patients should be screened for active TB disease
􀂾 Infection control measures
o All large health care facilities need to have an infection control (including airborne infection)
plan and a team for implementation of measures to prevent nosocomial transmission of TB and
other air-borne infections
􀂾 Statements to the press/media on MDR-TB and XDR-TB should be made with extreme
caution and after requisite verification and authentication

14. The Global Plan to Stop TB 2006–2015 has as its main targets:
•To meet the MDG target to have halted and begun to reverse the incidence of TB by 2015
•To meet the Stop TB partnerships own targets, to by 2015, halve prevalence and death rates from the 1990
baseline
•Over the ten years of the plan, 50 million people will be treated under DOTS Plus, 800,000 people will be
treated for MDR TB, and three million people with TB and HIV co–infection will start antiretroviral therapy.
•By 2010 simple tests for use at peripheral levels of the health system, will enable rapid, sensitive detection of
active TB at the first point of care, and by 2015 there will be tests to identify those at greatest risk of
progressing to active disease.
•The first new TB drug for 40 years will be introduced in 2010, and by 2015 the target will have nearly been
reached of a new regime that will achieve cure in 1–2 months, and that also will be effective against MDR TB
•By 2015 there will be the first of a series of new, safe, effective TB vaccines.
•There were also aims of involving communities and TB control featuring on the political agendas of countries.

15. Resources…
1. WHO. Multidrug-Resistant Tuberculosis, Online Q&A. February 2012. Available at
http://www.who.int/features/qa/79/en/index.html. Accessed November 16, 2012.
2. WHO. Partners call for increased commitment to tackle MDR-TB. 23 March 2011. Available at
http://www.who.int/mediacentre/news/releases/2011/TBday_20110322/en/index.html. Accessed November 16, 2012.
3. WHO. Tuberculosis. Available at http://www.who.int/topics/tuberculosis/en/. Accessed November 16, 2012.
4. WHO. Global Tuberculosis Report 2012, pgs. 2, 8, 16, 20, 41, 42, 44, 45, 50, 51, 57, 85. Available at
http://www.who.int/tb/publications/global_report/en/index.html. Accessed November 16, 2012.
5. Centers for Disease Control and Prevention, Trends in Tuberculosis. Available at
http://www.cdc.gov/tb/publications/factsheets/statistics/TBTrends.htm. Accessed November 16, 2014
6. WHO and Global Tuberculosis Control & Patient Care.The Beijing “Call For Action” On Tuberculosis Control and Patient
Care: Together Addressing the Global M/XDR-TB Epidemic. Available at
http://www.who.int/tb_beijingmeeting/media/en_call_for_action.pdf. Accessed November 16, 2012.