DRUG RESISTANT TUBERCULOSIS.pptx

8/18/2019 DRUG RESISTANT TUBERCULOSIS.pptx

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DRUG RESISTANTTUBERCULOSIS


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• Tuberculosis is a bacterial infection caused by

Mycobacterium TB

• The disease primarily aects lungs(pulmonary TB)

• Other organs include intestine, meninges, bones and

joints, lymph glands and skin


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DRUG RESISTANCE

Temporary/permanent capacity of the organism their progeny to remain !iable/to multiply inthe presence of the concentration of the drugthat "ould normally destroy/inhibit the gro"th

of other cells


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Types of #rug $esistant TB

MDR TB does not simply mean resistance to more thadrug, it speci%cally means resistance to at least bothisonia&id (') and rifampin ($)

XDR-TB is a rare type of M#$TB that is resistant to rifampicin, plus any +uorouinolone and at least one othree injectable secondline drugs(amikacin, kanamyccapreomycin)

TDR-TB refers to M-TB clinical strains that strains thasho" in !itro resistance to all %rst and second line dru


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.mergence of drug resistance

• treptomycin "as introduced in 0123 for the treatmentand the %rst case of Mresistant TB "as reported in 01

• *' "as introduced in 0156 and "as used alone or incombination "ith M/ 789 by the British Medical $eseacouncil

• The %rst case of M#$TB "as reported in 011: "ithresistance to *' and rifampicin in *e";ork

• The %rst case of


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• The presence of T#$TB "as %rst obser!ed in t"o pin taly in 6::>, the second report came from ran

•

n jan 6:06 there "as a report of 2 cases of T#$TB ndia


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8s per ?'O, about >-4@ of ne" TB patients in the "oha!e M#$TB-

8bout 1@ of M#$TB cases ha!e resistance to t"o othclasses of drugs, or are eAtensi!ely drug resistant TB(TB)

By March 6:0>, 2 countries had reported at least onTB case

?'O estimates that there "ere about :-5 million ne"TB cases in the "orld in 6:00

8bout 3:@ of the cases occurred in Bra&il, 9hina, ndi$ussia outh 8frica alone (CB$9D countries)

2@ of patients "ith M#$TB and 666@ of


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Eenesis of M#$TB

$esistance is a manmade ampli%cation of a naturalphenomenon-

nadeuate drug deli!ery is main cause of secondarresistance-

econdary drug resistance is the main cause of primdrug resistance due to transmission of resistant stra

M#$ due to spontaneous mutations is not possible agenes encoding resistance for anti TB are unlinked-


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Strains with geneticdrug resistance

Wild M. TB strain

Acquired drugresistance

Primary drugresistance

Spontaneous mutation

Selection: inadequate treatment

Transmission

Development o anti!tu"erculosis drug resistance

Pa"los!Mende# et al. W$%& '(()


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Mechanism of resistance

*' – 9hromosomally mediated

– Foss of catalase/peroAidase

– Mutation in mycolic acid synthesis

– $egulators of peroAide response

$ifampin – $educed binding to $*8 polymerase9lusters of mutations at C$ifampin $esistance

#etermining $egionD ($$#$)

– $educed 9ell "all permeability


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8ntiTB #rugs

First-Line

Second-Lin

• (') sonia&id

• ($) $ifampin

•

(G)7yra&inamide

• (.).thambutol

• treptom

• 9ycloser

• .thionam• 8mikacin

• 9ipro+oA


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7re!alence of drugresistant

in ndia• nitial M#$TB is probably !ery lo"

• M#$TB is more common in pre!iously treated TBpatients

• 8cuired resistance to $ifampicin >>>5@

• 8cuired resistance to *'5:55@

• trains resistant to $ifampicin are usually resistant *' "hereas !ice !ersa may not be al"ays true


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•#rugresistant TB is transmitted the same "

drugsusceptible TB•#rug resistance is di!ided into t"o typesH

- Primar resistance refers to cases initiallyinfected "ith resistant organisms

- Ac!"ired resistance de!elops during TB th

Drug-Resistant TB


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• Initia# resistance- presence of drug resistato one/more antiTB drugs in a ne" TB patien

"ho presents to a TB centre

• C$ronic %atient patient "ho remains smeapositi!e after completing a ?'O retreatmenregimen under super!ision


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Persons at Increased Ris& 'orDr"( Resistance

•'istory of treatment "ith TB drugs

•9ontacts of persons "ith drugresistant T

•mears or cultures remain positi!e despimonths of TB treatment

•$ecei!ed inadeuate treatment regimensI6 "eeks


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9linicians eAperience many challenges in the managemof patients "ith #$TB - uccess of treatment depends

0- Juality diagnosis testing

6- Medications , /. and drug regimens

>- The patient and the programme


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9linical signi%cance of drug

resistant TB• Treatment failure rate is 53 fold

• n case of resistance to *'/ treptomycin , the TB csuccessfully treated "ith 3 months of short coursechemotherapy

• $esistance to rifampicin is a serious problem• 8bout 4:1:@ of *' $ifampicin resistant bacilli

not respond/relapsed to treatment "ith short coursechemotherapy


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#iagnosis of drugresistant T• Kail to respond / deteriorate• 9linical criteria to con%rm failure / relapse after 6 cours

chemotherapy at least one of "hich is directly obser!ed

• 9on%rm "hether the diagnosis "as correct

• $epeat sputum 8KB and 9


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Management of drug resistant T

(#OTplus regime)• The regimen should include at least > drugs for "hich

patientLs organism ha!e pro!en in!itro susceptibility preferably that ha!e not been used to treat the patient

• 8fter diagnosis, the treatment of M#$TB is initiated a

designated #OT7lus sites, "hich are established in tcare centres (M9/large speciality hospitals)

• 7retreatment e!aluation since the drugs used are knoproduce ad!erse eects


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7retreatment e!aluation

0- #etailed history

6- 'eight, "eight

>- 9B9

2- Blood sugar

5- FKT

3- TKT

4- =rine $/. microscopy

- 7regnancy test

1- 9


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$egimen for M#$TB

INTENSI)E P*ASE+,-mont$s.

anamycin, le!o+oAacin, ethionamide, pyra&inamide,ethambutol, cycloserine

CONTINUATION P*ASE+/0 mont$s.

Fe!o+oAacin, ethionamide, ethambutol, cycloserine


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• 8s single daily dose under super!ision

• On sundays, the oral drugs "ill be administeredunsuper!ised "hereas injection anamycin "ill be o

• f any intolerance occurs, ethionamide, cycloserine a78 may be split into t"o, the morning doses taken super!ision e!ening doses selfadministered


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$egimen for


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• 8ll drugs are to be gi!en on a daily basis

• nj- 9apreomycin are to be gi!en for 3 days / "eek (nunday)

• 8ll morning doses are to be super!ised by the #OTpro!iders eAcept on sundays

• Oral medicines for are gi!en on aturday to be takenthe patient at home

• .mpty blisters of medicines taken on unday are to collected by #OT pro!ider


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• #irect obser!ation of treatment remains e!en moreimportant in


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Treatment of TB during pregnanc

•

Treated "ith *', $ifampicin and .thambutol for 6 monfollo"ed by *' $ifampicin for an additional 4 month

• f susceptible to *' $ifampicin, ethambutol can be safter the %rst month

• 7yra&inamide should be used only if resistance to other are documented

• treptomycin is 9/ in pregnancy as it may cause congendeafness

• Those taking *' should recei!e pyridoAin 0:65 mg oronce a day to pre!ent peripheral neuropathy


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9hildhood TB

• TB in children is mainly d/t failure of TB control in a

• 8n infant "hose mother has sputum smear positi!e has a high chance of becoming infected

• Because of less de!eloped immune system, children

5 years of age are more prone to de!elop the diseasemostly "ithin 6 years follo"ing infection

• 02 yrs


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#O8E. OK #$=E

• $ifampicin N 0:06mg/kg

• *' 0:mg/kg

• .thambutol 6:65 mg/kg

• 7G8 >:>5mg/kg

• treptomycin 05mg/kg


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' TB•

The ' !irus damages the bodyLs natural defences theimmune systemand accelerates the speed at "hich TBprogresses from harmless infection to life threatening co

• ' TB interact in se!eral "ays

$eacti!ation of latent infection 65>: times more risk,because of the stoppage of "orking of the immune system

' 7rimary infection ' patients are at risk of being ne"l

infected "ith TB because their "eakened immune systemthem more !ulnerable


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$ecurring infection ' patients "ho ha!e been cureTB infection are more at risk of de!eloping TB again

DIAGNOSIS OF TB IN *I) PATIENTS

n ' patients at early stages, the symptoms of TB are sto those "ithout ' infection- 'o"e!er the diagnosis of using the standard diagnostic tools can be diicult in thead!anced ' infection because,

0- putum smear N!e, sputum culture to con%rm6- Tuberculin test N!e

>- Fess ca!itations in the 9


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DIAGNOSIS OF *I) IN TB PATIENTS

• n areas "here there is high pre!alence of ', 'testing should be systematically oered to all TB

patients, including children• erological testing

• 7atients should be counselled on beha!iour risk andmethods to pre!ent transmitting or acuiring the inf


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Bedauiline Na no!el promisindisco!ery in M#$TB

• #isco!ered in 6::2 by Pohnson Pohnson !ia screening protomore than 4:,::: chemicals by inhibition of gro"th againstmycobacterium smegmatis, a more rapidly gro"ing mycobactcompared to MTB

• Kirst described at the nter science 9onference on 8ntimicrob

agents and chemotherapy (9889) in 6::2• MO8 inhibit proton pump of 8T7 synthase in MTB- 8T7 synt

an en&yme that is essential for the generation of energy in MTBedauiline binds to the csubunit of 8T7 synthase inhibiting 8synthesis causing death of MTB


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• ndication as a part of combination therapy in adu"ith M#$TB "hen other alternati!es are not a!aila

• #osage and administration initial dose of 2::mg odaily for 6 "eeks follo"ed by 6::mg > times per "e66"eeks- t is supplied as 0::mg tablets to be takenfood and s"allo"ed "hole "ith "ater

• 8d!erse eects nausea, arthralgia, diarrhoea, paieAtremities and hyperuricemia


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8cuired resistance of MTB toBedauiline

• denti%ed in 6:02

• #ue to mutations in $!o34 , a transcriptional repreof the genes encoding Mmp5Mm7F5 eQuA pump- based resistance "as identi%ed in paired isolates fro

patients treated "ith B#J as "ell as in mice, in "hic"as con%rmed to decrease the bactericidal eicacy- eQuA inhibitors !erapamil reserpine decreasesminimum inhibitory concentration of B#J but failedincrease the bactericidal eect of B#J in mice "aunable to re!erse the eQuA based resistance in!i!o


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• n addition to B#J, delamanid and line&olid are apprby the = Kood and #rug 8dministration(K#8) and t.uropean Medicines 8gency that may oer therapeu

solution to T#$TB

• n a recent update on T#$TB, 05 cases "ith resistaall drugs tested ha!e been reported and 5 patients d


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7re!ention of #$TB

• nitial treatment "ith standardi&ed regimens ('$G.

• #irectly obser!ed therapy (#OT)

• #rug susceptibility testing for all retreatment cases

• nfection control precautions

• Monitor drug resistance through sur!eys• .ecti!e contact management


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TO7 TB T$8T.E; • Faunched in 6::3

• t is to be implemented o!er the neAt 0: years asdescribed in the Elobal plan to stop TB in 6::36:05

• t focuses on 5 principal indicators that are used tomeasure the implementation and the impact of TB c case detection, treatment, success, incidence,

pre!alence and deaths


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Targets

• By 6:05 the global burden of TB "ill be reduced byrelati!e to 011: le!els- This means reducing pre!ale

05: per 0::::: or lo"er and deaths to 05 per 0::: year or lo"er by 6:05

• The number of people dying from TB in 6:05 shouldless than approAimately 0 million including thosecoinfected "ith '

•

By 6:5: the global incidence of TB disease "ill be lthan or eual to 0 case per million population per ye


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9OM7O*.*T OK T'. T$8T.E; 8*#M7F.M.*T8TO* 877$O89'.

0- 7ursuing high uality #OT eApansion and enhanc

•. 7olitical commitments "ith increased and sustained%nancing

•. 9ase detection through ualityassured bacteriology

•. tandardi&ed treatment "ith super!ision and patiensupport

•. 8n eecti!e drug supply and management system

•. Monitoring and e!aluation system and impactmeasurement


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6- 8ddressing TB/', M#$TB and other challenges

• mplement collaborate TB/' acti!ities

• 7re!ent and control M#$TB

• 8ddress prisoners, refugees, other high risk groups andspecial situations

>- 9ontributing to health system strengthening

• 8cti!ely participate in eorts to impro!e system "ide phuman resources, %nancing, management, ser!ice deli!

and information system• hare inno!ations that strengthen health systems, inclu

the practical approach to lung health(78F)

• 8dapt inno!ations from other %elds


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2- .ngaging all care pro!iders

• 7ublicpublic and publicpri!ate miA approaches

•

mplement international standards for TB care5- .mpo"ering people "ith TB and communities

• 8d!ocacy , communication and social mobilisation

• 9ommunity participation in TB care

• 7atientsL charter for TB care

3- .nabling and promoting research• 7rogramme based operational research

• $esearch to de!elop ne" diagnostics, drugs and !ac


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$*T97 daily treatment regim

T%e o' TBcases

Treatmentre(imen IP

Treatmentre(imenCP

*.? 6'$G. 2'$.

7$.O=F;T$.8T.#

6'$G.R0'$. 5'$.


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#aily dosage schedule for adu 2ei($t

cate(or

N"m3er

o'

cons"med

ta3#ets to

3e

in4ection

stre

cin

7 97

'$G. '$.

45/05:/2::/ 645mg/tab

45/05:/645 mg/tab Eram

65>1 kg 6 6 :-5 g

2:52 kg > > :-45 g

5531 kg 2 2 0 g


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THE END TB STRATEGY 2016-2035VISION A world free of TB - Zero deaths, disease and suering due to TB

GOA! En" t#e G$%&a$ TB E'i"e(i)*I!ESTONES +OR 2025 75% reduction in TB deaths (compared with 2!5" 5% reduction in TB incidence rate (less than 55 T!, population" #o aected families facing catastrophic costs due

TARGETS +OR 2035 $5% reduction in TB deaths (compared with 2!5" $% reduction in TB incidence rate (less than ! TB ca

!, population" #o aected families facing catastrophic costs due to T

,RINI,!ES - o&ernment stewardship and accounta'ilit, with monitoring a - )trong coalition with ci&il societ organi*ations and communit - +rotection and promotion of human rights, ethics and euit - Adaptation of the strateg and targets at countr le&el, with gcolla'oration

• ,I!!ARS AND O*,ONENTS


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• 1. INTEGRATED/ ,ATIENT-ENTRED ARE AND ,REVENTIONA .arl diagnosis of TB including uni&ersal drug suscepti'ilit testing/ and sstemof contacts and high-ris0 groupsB Treatment of all people with TB including drug-resistant TB/ and patient supporA 1olla'orati&e TB34 acti&ities and management of comor'iditiesB +re&enti&e treatment of persons at high-ris0/ and &accination against TB

• 2. BO!D ,O!IIES AND S,,ORTIVE SYSTE*SA +olitical commitment with adeuate resources for TB care and pre&entionB .ngagement of communities, ci&il societ organi*ations, and pu'lic and pri&ate1 6ni&ersal 3ealth 1o&erage polic and regulator framewor0s for case noticatiregistration,

ualit and rational use of medicines, and infection control8 )ocial protection, po&ert alle&iation and actions on other determinants of TB

• 3. INTENSI+IED RESEARH AND INNOVATIONA 8isco&er, de&elopment and rapid upta0e of new tools, inter&entions and strateB 9esearch to optimi*e implementation and impact, and promote inno&ations


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DRUG RESISTANT TUBERCULOSIS.pptx

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