MDR TB Case

PresentationPresented By

Dr. Sata Ram Bhakhar

In Guidance of

Dr K.K. Meena Sir

Professor, PSM

Name- Ram lal, Age- 35 year, Sex- Male,

Religion- Hindu, Address- Bhojawas,

Kotputali, Jaipur (rajasthan).

Chief Complaint:

C/o fever, cough with expectoration,

loss of appetite,

weight loss,

weakness and

breathlessness on exertion, all complaint

since 4 weeks

History of Present Illness

Patient was apparently well before 4

weeks then he developed cough with

expectoration which was severe at night

& associated with breathlessness, irregular

low grade fever & sweating at night, loss

of appetite, weight loss, weakness &

occasional chest pain since than.

History of Past Illness

Pt has history pulmonary tuberculosis a

year ago for which he was treated for six

months with improvement. The

antituberculosis drugs were stopped 6

months before admission. No history any

other illness.

Personal History

Vegetarian, alcoholic since 4years,

smoker since 8-9 year , 1packet of bidi per

day.

Family History

His father died of tuberculosis 10 years

ago.

General Physical Examination

Pt is conscious , oriented to time, place,

person.

Poor built and cachexic look.

Pallor present

Pedal oedema present

Clubbing, icterus, cyanosis not present.

No peripheral Lymphadenopathy, no

hepatomegaly, no splenomegaly

Vitals

Pulse- 96b/min, RR-26/min, Temp- 101.6F

Respiratory System

Examination

Dullness on percussion & crypts present in

rt side of back of chest.

Air entry decreased on rt chest.

P/A Examination

Soft, Nontendor , No Splenomegaly , no

Hepatomegaly .

CVS Examination

S1 S2 Normal, No murmur

CNS Examination

Pt. conscious , oriented to time, place,

person

No neurological sign or symptoms present.

Laboratory Findings

TLC-11300, P62L11E16M10B1

RBS-97mmg/dl

HIV-Negative

Sputum Examination- Positive For AFB

CXR- Consolidation in Rt middle lobe

present, Mediastinal lymph node

enlarged.

Culture & DST

Mycobacterial culture by Radiometric

method (BACTEC-450) & Drug sensitivity

by Radiometric method showed bacilli

were resistant to H, R, Z. E and

streptomycin (S) but were sensitive to

kanamycin, ethionamide, ofl oxacilin,

cycloserin and para-aminosalicylic acid

(PAS).

Drug resistance - types When drug resistance is demonstrated in a

patient who has never received anti-TB treatment previously, it is termed primary (Initial) resistance, i.e. TB patient’s initial M.TB population resistant to drugs

Secondary (Acquired) resistance is that which occurs as a result of specific previous treatment, i.e. Drug-resistant M. TB in initial population, selected by inappropriate drug use (inadequate treatment or non-adherence)

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)

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 2nd-line injectable drug

(amikacin, kanamycin, or capreomycin

Single Isoniazid or Rifampicin resistance is

not MDR – TB.

MDR TB is a laboratory diagnosis, Not a

Clinical assumption

Resistance to all first-line anti-TB drugs

(FLD) and second-line anti-TB drugs (SLD)

that were tested.

Global

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

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

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

BIOLOGICAL FACTORS :

Initial bacillary population

Local factors in host favourable for multiplication of bacilli

Presence of drug in insufficient concentration

Irregular intake

inadequate duration

Neglect of disease

Ignorance

Genesis of MDR TB

Resistance is a man-made amplification of a natural phenomenon. i.e. Selection & proliferation of pre existing mutants due to man made factors leads to drug resistance.

Inadequate drug delivery is main cause of secondary drug resistance.

Secondary drug resistance is the main cause of primary drug resistance due to transmission of resistant strains.

MDR due to spontaneous mutations is not possible as the genes encoding resistance for anti TB are unlinked.

Doses of TB Drugs

Daily HRZES- 5,10,25,15,15 mg/kg

3 times per week HRZES- 10, 10, 35, 30, 15

Treatment:

Dose as per weight ,Baseline LFT, KFT

New TB cases:

2(EHRZ) + 4(HR)

Retreatment TB cases:

2(SHERZ)+1(EHRZ)+5(HRE)

Suspicion of MDR 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.

Extra pulmonary TB not responding to standard ATT regime

Before starting of TtCulture dst of all 1st and 2nd line drugs prior to Treatment of MDR TB. +

Individualised treatment.

Diagnosis…

Conventional LJ culture DST – Gold standard

DST- modified proportion method. (4 to 6

weeks for culture & 3 weeks post culture for

dst).

PCR based LPA (line probe assay) – DST result

within 72 hours.

Other methods – (Liquid cultures)BACTEC 460,

MGIT 960 (14 days + 9 days for dst) , etc.

The Xpert MTB/RIF The Xpert MTB/RIF is a

cartridge-based,

automated diagnostic test

that can identify

Mycobacterium

tuberculosis (MTB)DNA and

resistance to rifampicin

(RIF)by nucleic acid

amplification

technique(NAAT )

Result within 2 hours.

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.

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 (PMDT) 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

Adverse Drug Reaction

Nausea and vomiting - Eto, PAS, Z, E

Giddiness - Aminoglycosides, Eto, Fqand/or Z

Ocular toxicity - E

Renal toxicity - Aminoglycosides

Arthralgia - Z and/or Fq

Cutaneous reactions - pruritis or rash- any of the drugs used.

Hepatitis - Z & Eto

Peripheral neuropathy - Cs, Eto

Seizures - Fq and/or Cs

Psychiatric disturbances – Cs, Fq and/or

Eto

Vestibulo-auditory disturbances -

Aminoglycosides

Hypothyroidism - PAS and/or Eto

Pre treatment evaluation for

MDR TB

PMDT (Dots Plus)

Always Remember