MDR TB

Views:
 
Category: Education
     
 

Presentation Description

MDR TB presentation simplifying the salient aspects of mdr tb.

Comments

Presentation Transcript

MDR TUBERCULOSIS - An overview:

MDR TUBERCULOSIS - An overview Dr. Gyanshankar Mishra MD (Pulmonary Medicine), DNB (Respiratory Diseases) Assistant Professor , Department of Pulmonary Medicine, GMC Nagpur

SYNOPSIS:

SYNOPSIS Drug resistance - Types & Definitions Epidemiology Mechanism & Causes of drug resistance Management of MDR TB Clinical case illustration

Drug Resistant TUBERCULOSIS:

Drug Resistant TUBERCULOSIS Types & Definitions

Drug resistance - types:

Drug resistance - types When drug resistance is demonstrated in a patient who has never received anti-TB treatment previously, it is termed primary resistance. Acquired resistance is that which occurs as a result of specific previous treatment. The level of primary resistance in the community is considered to reflect the efficacy of control measures in the past , while the level of acquired resistance is a measure of on-going TB control measures.

DRUG RESISTANT –TB (DR-TB):

DRUG RESISTANT –TB (DR-TB) Drug resistant TB Mono resistance Poly resistance Multi Drug Resistant TB(MDR- TB) Extensive Drug Resistant TB (XDR-TB ) Total Drug Resistance (TDR – TB)

DRUG RESISTANT- TB(DR-TB) :

DRUG RESISTANT- TB(DR-TB) Mono Drug Resistance (Resistance to single first line ATT) Poly Drug Resistance (Resistance to two or more first line ATT except MDR-TB)

PowerPoint Presentation:

Multi-drug resistant tuberculosis (MDR TB) is defined as resistance to isoniazid and Rifampicin ( a laboratory diagnosis ). Extensively drug resistant TB (XDR-TB ) is MDR + resistance to any fluoroquinolone + resistance to at least one 2 nd -line injectable drug ( amikacin , kanamycin , or capreomycin )

TDR: Total Drug Resistance:

TDR: Total Drug Resistance Resistance to all first-line anti-TB drugs (FLD) and second-line anti-TB drugs (SLD) that were tested.

PowerPoint Presentation:

2012

Drug Resistant TUBERCULOSIS:

Drug Resistant TUBERCULOSIS EPIDEMIOLOGY

In our country…:

In our country…

Global Scenario:

Global Scenario Globally, it is estimated that 3.3% of all new TB cases had MDR-TB in 2009 Each year, about 440,000 MDR-TB cases are estimated to emerge, and 150,000 persons with MDR-TB die. There are an estimated 25,000 cases of XDR-TB emerging every year.

India MDR TB Data:

India MDR TB Data State representative community based drug resistance surveys estimate the prevalence of Multidrug resistant TB (MDR-TB) to be ~ 3% among new TB cases and 12-17% among previously-treated TB cases .

India XDR TB data:

India XDR TB data *NDTB center, 18400 isolates, 0.89% of all MDR were XDR ** Hinduja Hospital, Mumbai, 3204 samples, 32% MDR, 8% of MDR were XDR *** KGMU, Lucknow : Among 68 MDR, 5 ( 7.4% ) were XDR * Ind J Tub 2008; 55:104 ** Sushil Jain et al ATS 2007 meet Abstract 1398 *** Mondal R et al. Em . Inf. Dis 2007; 13:9

Drug Resistant TUBERCULOSIS:

Drug Resistant TUBERCULOSIS MECHANISMS & FACTORS

Mechanisims of Drug Resistance in Tuberculosis:

Mechanisims of Drug Resistance in Tuberculosis

DRUG RESISTANCE : MOLECULAR BASIS:

DRUG RESISTANCE : MOLECULAR BASIS DRUG RESISTANT ISOLATES SHOW MUTATION IN GENES INH : kat g, inhA RIFAMPICIN : rpoB STREPTOMYCIN - rpsL ETHIONAMIDE - inhA FLUOROQUINOLONES - gyrA, gyrB DNA probes using genetic information have been devised

FACTORS RESPONSIBLE FOR DEVELOPMENT OF DRUG RESISTANCE:

FACTORS RESPONSIBLE FOR DEVELOPMENT OF DRUG RESISTANCE CLINICAL / OPERATIONAL FACTORS Unreliable treatment regimen by doctors Lesser number of drugs Inadequate dosage / duration Addition of a single drug in failing regimen Easy availability of drugs in private sector Poor drug supply Poor quality of drugs : poor bioavailability

Published Evidence:

Published Evidence In this study prescriptions issued by allopathic postgraduate physicians were collected from patients to judge accuracy of prescribing practices. Out of 101 prescriptions, 71 (70%) were faulty in respect of drug doses as recommended by WHO.

Published evidence..:

Published evidence.. 187 post-graduate doctors in Delhi were using 102 different regimen for treatment of TB Singla N et al. Int J TB Lung Dis 1998; 2: 384-389 100 doctors prescribed 80 ATT regimes. Uplekar MW et. al. (1991) Tubercle:72:284-90

Published evidence..:

Published evidence.. “Only 6 of the 106 respondents wrote a prescription (for TB) with a correct drug regimen.”.. Udwadia ZF, Pinto LM, Uplekar MW (2010) Tuberculosis Management by Private Practitioners in Mumbai, India: Has Anything Changed in Two Decades? PLoS ONE 5(8): e12023. doi:10.1371/journal.pone.0012023

WHAT CAN BE DONE?:

WHAT CAN BE DONE? Treatment: Daily regime / Once a day dosing/ Dose as per weight/Baseline LFT, KFT New TB cases: 2(EHRZ) + 4(HR) Retreatment TB cases: 2(SHERZ)+1(EHRZ)+5(HRE)

What can be done?..:

What can be done?.. Treatment…. Daily Dose (mg/kg) as per weight (WHO Recommended):

FACTORS RESPONSIBLE FOR DEVELOPMENT OF DRUG RESISTANCE:

FACTORS RESPONSIBLE FOR DEVELOPMENT OF DRUG RESISTANCE BIOLOGICAL FACTORS : Initial bacillary population Local factors in host favourable for multiplication of bacilli Presence of drug in insufficient concentration

Why this information?:

Why this information? Suspect MDR TB if: There is extensive tuberculosis at the start of treatment. The patient is suffering from immunocompromised state like HIV. The patient has recived ATT in suboptimal dosing.

FACTORS RESPONSIBLE FOR DEVELOPMENTOF DRUG RESISTANCE:

FACTORS RESPONSIBLE FOR DEVELOPMENTOF DRUG RESISTANCE SOCIOLOGICAL FACTORS : Irregular intake inadequate duration Neglect of disease Ignorance

What can be done?:

What can be done? Patient counseling at the start of treatment

PowerPoint Presentation:

Selection & proliferation of pre existing mutants due to man made factors leads to drug resistance. Multiple drug resistant strains result from the step-wise accumulation of individual resistance elements therefore MDR-TB is MAN-MADE

Drug Resistant TUBERCULOSIS:

Drug Resistant TUBERCULOSIS MANAGEMENT PRINCIPLES Suspicion, Diagnosis & Treatment

Suspicion of MDR TB:

Suspicion of MDR TB When should we suspect drug resistant TB? A close contact of Drug Resistant TB case. Treatment failures. All retreatment cases. No sputum conversion after initial 2 months of ATT. Extensive disease at start of treatment. All HIV patients with TB. Extrapulmonary TB not responding to standard ATT regime.

Diagnosis – Accredited laboratory:

Diagnosis – Accredited laboratory

Diagnosis…:

Diagnosis… Tests available are: Conventional LJ culture DST – Gold standard DST- modified proportion method. (4 to 6 weeks for cultur e & 3 weeks post culture for dst ). PCR based LPA (line probe assay) – DST result within 72 hours. Newer methods like gene-expert – result within 2 hours. Other methods – BACTEC 460, MGIT 960 (14 days + 9 days for dst ) , etc.

Treatment – why important?:

Treatment – why important?

Treatment – why important?:

Treatment – why important?

Treatment…:

Treatment… “Recently, a letter to Clinical Infectious Disease Journal in December 2011 described 4 patients from Mumbai, India with “totally drug resistant” tuberculosis (coined “TDR-TB” from earlier reports) i.e. resistant to all firstline and second-line drugs tested.” “A careful audit of their prescriptions revealed that these 3 patients had received erratic, unsupervised secondline drugs, added individually and often in incorrect doses, from multiple private practitioners (on average from 4 physicians during a 18-month period) in an attempt to cure their multi-drug resistant (MDR) tuberculosis.”

Drugs in MDR TB Management :

Drugs in MDR TB Management 1st line drugs: (HR)ZE Injectable : Km , Cm, Am Fluoroquinolone : Ofx , Mfx , Lfx , Gfx . Other 2nd line drugs: Cs, PAS, Pto/Eto Unclear drugs: Clarithro , CoA , Clofazimine , Linezolid , High dose INH Most efficacious and best tolerated Bactericidal Highly B actericidal Less efficacious and poorly tolerated Weak anti-TB action

Important principles of MDR-TB regimen design :

Important principles of MDR-TB regimen design Use at least 4 reliable drugs . Do not use drugs with cross resistance . Eliminate drugs that are not safe for the patient. Include drugs from Groups 1-5 in a hierarchical order. Monitor and manage adverse effects of drugs. Never add a single drug to failing regime.

PowerPoint Presentation:

General Treatment Principles Provide 18-24 months’ treatment, always with intensive phase of at least 6 months ( current WHO guidelines -8 months). Provide DOT therapy. Warn patients about possible side-effects. Manage side-effects appropriately. Perform cultures monthly.

Regimen under DOTS Plus Programme in India :

Regimen under DOTS Plus Programme in India INITIAL INTENSIVE PHASE : 6- 9 months Inj. Kanamycin Tab Ethionamide Tab Ofloxacin Tab. Pyrazinamide Tab. Ethambutol Cap Cycloserine CONTINUATION PHASE : 18 months Tab Ethionamide Tab Ofloxacin Tab Ethambutol Cap Cycloserine

DOTS PLUS DAILY REGIME:

DOTS PLUS DAILY REGIME

Drug Resistant TUBERCULOSIS:

Drug Resistant TUBERCULOSIS CASE ILLUSTRATION

Clinical Case :

Clinical Case 50 years old, 62 Kg patient H/o Irregular treatment for 6-7 months Now sputum AFB smear Positive Put on 4 drug ATT (H 300mg, R 450 mg, E 800 mg and Z 1500 mg).

Clinical Case Contd...:

Clinical Case Contd... Sputum continues to be positive after 5 months of treatment Sputum sent for AFB culture/sensitivity and inj. kanamycin added by the treating physician. Sputum continues to be positive after 3 months

Clinical Case Contd...:

Clinical Case Contd... DST: MDR (resistance to H+R) INH and RIF stopped and ethionamide & ofloxacin added After 4 months sputum is still positive DST: resistance to H, R, Kana, Oflox (XDR-TB)

Clinical Case Contd...:

Clinical Case Contd... Lesson learnt from case Inadequate dosages. Wrong regime at the start . Lack of initial suspicion of MDR suspect and hence delay in sending culture dst / and initiating correct regime. Adding only single drugs to failing regimen Improper regime of MDR TB: Regime did not include 4 reliable core drugs after diagnosis of MDR TB. Referral to a specialist was not done at any stage. Can lead to MDR / XDR -TB

Carry Home Message:

Carry Home Message Better to Prevent MDR-TB Regular Drugs Appropriate Dosages Full Duration Health Education Direct Supervision Referral to a specialist centre

Thank you:

Thank you

authorStream Live Help