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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.
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
Respiratory System
Examination
Dullness on percussion & crypts present in
rt side of back of chest.
Air entry decreased on rt chest.
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.
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