Mdr tb & xdr tb ppt.

SILAJIT DUTTA BPharm

3rd Year 6th SemesterGuided by

Mr RAJA CHAKRAVERTYAsst Professor

Bengal College of Pharmaceutical Sciences and Research

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 amp 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 ie ofloxacin ciprofloxacin and levofloxacin and at least one of three injectable second line anti tubercular drugs ie amikacin kanamycin and capreomycin

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)

Clinical factors promoting resistance

bull Delayed diagnosis and isolationDelayed diagnosis and isolationbull Inappropriate drug regimenInappropriate drug regimen

bull Inadequate initial therapyInadequate initial therapybull Incomplete course of treatmentIncomplete course of treatmentbull Inappropriate treatment modificationsInappropriate treatment modificationsbull Adding single drug to a failing regimenAdding single drug to a failing regimenbull Inappropriate use of chemoprophylaxisInappropriate use of chemoprophylaxis

bull Poor adherence and incomplete FUPoor adherence and incomplete FUbull Failure to isolate MDR TB patientsFailure to isolate MDR TB patientsbull Failure to employ DOTFailure to employ DOTbull Over the counter anti TBOver the counter anti TBbull Faked drugsFaked drugs

Bacteria coughedout in sputum

Inhalation of bacteria

Bacteria reach lungsenter macrophages

Bacteria reproducein macrophages

Lesion begins to form(caseous necrosis)

Activatedmacrophages

Bacteria stop growing lesion calcifies

Immunosuppression

Reactivation

Lesionliquefies

Deadphagocytesnecrosis

M tuberculosis

PhagocytesT cells andB cellstrying tokill bacteria

DEATH

Spread tobloodorgans

Steps in the development of tuberculosis

6

TB TESTING

1 XPERT Test

The Xpert MTBRIF 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 JerseyThe Xpert (GeneXpert) MTBRIF 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 copy GHE

Tuberculin skin test (20 mm in diameter) was seen within 72

hours

PPD Skin TestPurified Protein Derivative

Standard (PPD)

Mantoux Skin Test

2 mm2 mm

2 TB Skin Test2 TB Skin Test

Positive Tuberculin Skin Test

Categories of Antituberculosis Drugs WHO

bull Group 1 ndash First-line drugs Isoniazid rifampicin ethambutol pyrazinamide

bull Group 2 - Injectable agents Kanamycin amikacin capreomycin streptomycin

bull Group 3 - Fluoroquinolones Levofloxacin moxifloxacin ofloxacin

bull Group 4 - Oral bacteriostatic agents Ethionamide cycloserine para-aminosalicylic acid (PAS) prothionamide terizadone

bull Group 5 ndash Unclear role Clofazamine linezolid amoxicillinclavulanate Imipenemcilastatin thioacetazone high-dose isoniazid clarithromycin

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 copyWHOTBPGary Hampton

Causes of inadequate TB treatment

Doctors - as a cause of inadequate TB treatment

Inappropriate guidelines

Noncompliance with guidelines

Absence of guidelinesDrugs - as a cause of inadequate TB treatment

Poor quality

Irregular supply

Wrong delivery (dosecombination)

Drugs are unsuitable due to drug resistance

Patients - as a cause of inadequate TB treatment

Lack of informationLack of money for treatment andor transportActual or presumed side effectsLack of commitment to a long course of drugsMalabsorptionSocial barriers

Public health responsibilities of health care providers

1048766 Health care facilitiespractitioners managing confirmed MDR-TB patients should inform their respective District TB Officer regarding treatment initiation and outcome of all MDR-TB cases

1048766 prior to treatment initiation and on all follow up visits the patient and family members should be counseled on all aspects of MDR-TB

1048766 All house hold contacts of the MDR-TB patients should be screened for active TB disease

1048766 Infection control measureso 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

1048766 Statements to the pressmedia on MDR-TB and XDR-TB should be made with extreme caution and after requisite verification and authentication

The Global Plan to Stop TB 2006ndash2015 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 800000 people will be treated for MDR TB and three million people with TB and HIV condashinfection 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 1ndash2 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

Resourceshellip

1 WHO Multidrug-Resistant Tuberculosis Online QampA February 2012 Available at httpwwwwhointfeaturesqa79enindexhtml Accessed November 16 2012 2 WHO Partners call for increased commitment to tackle MDR-TB 23 March 2011 Available at httpwwwwhointmediacentrenewsreleases2011TBday_20110322enindexhtml Accessed November 16 2012 3 WHO Tuberculosis Available at httpwwwwhointtopicstuberculosisen 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 httpwwwwhointtbpublicationsglobal_reportenindexhtml Accessed November 16 2012 5 Centers for Disease Control and Prevention Trends in Tuberculosis Available at httpwwwcdcgovtbpublicationsfactsheetsstatisticsTBTrendshtm Accessed November 16 2014 6 WHO and Global Tuberculosis Control amp Patient CareThe Beijing ldquoCall For Actionrdquo On Tuberculosis Control and Patient Care Together Addressing the Global MXDR-TB Epidemic Available at httpwwwwhointtb_beijingmeetingmediaen_call_for_actionpdf Accessed November 16 2012