27. rational use of antibiotics

8/9/2019 27. Rational Use of Antibiotics

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RATIONAL USE OFRATIONAL USE OF

ANTIBIOTICSANTIBIOTICS

dr. Siti Supartidr. Siti Suparti

Medical School Padjadjaran UniversityMedical School Padjadjaran University

Department of Pharmacology & TherapyDepartment of Pharmacology & Therapy


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References :References :

1. Lippincotts !ll"strated #evie$s %1. Lippincotts !ll"strated #evie$s %Pharmacology 'Pharmacology 'ndndeded

()hapter '*+()hapter '*+

'. ,"-" Pedoman "liah /arma-o-lini-'. ,"-" Pedoman "liah /arma-o-lini-

/arma-ologi !!!/arma-ologi !!!

0ilid 1 edisi '0ilid 1 edisi ' Prof. D#. erri S. Sastramihardja dr.Prof. D#. erri S. Sastramihardja dr.

Sp/Sp/


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2 medical doctor has to -no$ the2 medical doctor has to -no$ the

definite clinical pharmacology ofdefinite clinical pharmacology ofanti3iotics ho$ to select and "seanti3iotics ho$ to select and "se

them rationally.them rationally.

456 of inpatient individ"als has456 of inpatient individ"als has

3een given anti3iotics3een given anti3iotics


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Side effectSide effect Resistance

Definition Ideal antibiotics

Classification SpectraIn vitro

Chemical structures

Mechanism of action

AB


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DEFINITIONDEFINITION

2, are chemical s"3stances o3tained from2, are chemical s"3stances o3tained from

micro3es7microorganisms (3acteria f"ngimicro3es7microorganisms (3acteria f"ngi

actinomycetes+ that a3le to inhi3it oractinomycetes+ that a3le to inhi3it or

eradicate the gro$th of the othereradicate the gro$th of the other

microorganisms.microorganisms.2ntimicro3ial2ntimicro3ial all antiinfectionsall antiinfections

semisyntheticsemisynthetic syntheticsynthetic

nat"renat"re anti3ioticsanti3iotics


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IDEAL ANTIBIOTICS CRITERIAIDEAL ANTIBIOTICS CRITERIA

1.1.

Most selective most effective to infectiedMost selective most effective to infectiedmicroorganismsmicroorganisms

'.'. More 3actericidal effect in the site ofMore 3actericidal effect in the site ofactionaction

4.4. 2nti3acterial effect is not interfered 3y2nti3acterial effect is not interfered 3y3ody fl"id e8"date plasma protein or3ody fl"id e8"date plasma protein oren9ymes and persist for a long d"rationen9ymes and persist for a long d"rationin the 3loodin the 3lood

:.:. Minimal to8icityMinimal to8icity

;.;. #esistance develops slo$ly#esistance develops slo$ly. #eacha3le cost#eacha3le cost


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In vitroIn vitro

1. Primary 3acteriostatic effect1. Primary 3acteriostatic effect

inhi3it theinhi3it the

gro$th of m.ogro$th of m.o

S"lfonamide tetrac chlolamphS"lfonamide tetrac chlolampherythromycin (lo$ concentration+erythromycin (lo$ concentration+

lincomycin clindamycin and f"sidic acidlincomycin clindamycin and f"sidic acid'. Primary ,actericidal ?ffects'. Primary ,actericidal ?ffects

?radicate7-ill?radicate7-ill

Pen cef aminoglic erythromycin (highPen cef aminoglic erythromycin (highconcentration+ cotrima9ol. #ifampisinconcentration+ cotrima9ol. #ifampisinand van-omycin.and van-omycin.

Those classification is not a3sol"te 3"tThose classification is not a3sol"te 3"t

relativerelative


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SPECTRUM OF AB EFFECTSSPECTRUM OF AB EFFECTS

1. @arro$ spectr"m anti3iotics (@S2,+1. @arro$ spectr"m anti3iotics (@S2,+

Main effect % sensitive for gram positiveMain effect % sensitive for gram positive3acteria and 3acil3acteria and 3acil

e.g. % Pen. = Pen. #esistent penicillinasee.g. % Pen. = Pen. #esistent penicillinasesemisynthetics 3acitracin macrolidessemisynthetics 3acitracin macrolides

lincomycin vancomycinlincomycin vancomycin'. ,road Spectr"m 2nti3iotics (,S2,+'. ,road Spectr"m 2nti3iotics (,S2,+

Main effect % sensitive for gram positiveMain effect % sensitive for gram positiveand gram negative 3acteriaeand gram negative 3acteriae

e.g. % Pen. (ampicillin and amo8ycillin+e.g. % Pen. (ampicillin and amo8ycillin+cefalosporins tetracyclinscefalosporins tetracyclinschloramphenicol trimetroprim andchloramphenicol trimetroprim ands"lfonamidess"lfonamides


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Aidely "sed of ,S2,Aidely "sed of ,S2, an "m3rella inan "m3rella in

treating the "nidentified 3acterialtreating the "nidentified 3acterial

infectioninfection

resistanceresistance

#?S!ST2@)? and#?S!ST2@)? and

M?)2@!SM B/ 2)T!B@ recall inM?)2@!SM B/ 2)T!B@ recall in

micro3iologymicro3iology


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SIDE EFFECTSSIDE EFFECTS

1.1. 2LL?#=!) #?2)T!B@2LL?#=!) #?2)T!B@

'.'. TBC!) #?2)T!B@TBC!) #?2)T!B@Direct effects in "nproper dose e.g. %Direct effects in "nproper dose e.g. %aminoglycosidesaminoglycosides

4.4. SUP?#!@/?)T!B@ % ne$ infection ca"sed 3ySUP?#!@/?)T!B@ % ne$ infection ca"sed 3y

pathogen micro3es or f"ngi d"ring 2,pathogen micro3es or f"ngi d"ring 2,therapy to primary infection.therapy to primary infection.

SUP?#!@/?)T!B@ % fre"entSUP?#!@/?)T!B@ % fre"ent

potentially harmed ris-potentially harmed ris-

)a"sa % ?ntero3acter Pse"domonas)a"sa % ?ntero3acter Pse"domonas)andida and other f"ngi. Those agents are)andida and other f"ngi. Those agents arediffic"lt to 3e eradicated 3y to day availa3lediffic"lt to 3e eradicated 3y to day availa3leanti3iotics.anti3iotics.


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AVOIDING SUPERINFECTIONAVOIDING SUPERINFECTION

1.1. Stop the giving anti3ioticsStop the giving anti3iotics'.'. )"lt"ring the microorganism that)"lt"ring the microorganism that

ca"ses s"perinfectionca"ses s"perinfection

4.4. Treatment according to 3acterialTreatment according to 3acterialidentification and sensitivity testidentification and sensitivity test

The specimen $as ta-en from fecesThe specimen $as ta-en from fecesand secretion of "pper resoiratoryand secretion of "pper resoiratorytract to 3e analy9edtract to 3e analy9ed


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RATIONAL THERAP OF ANTIBIOTICSRATIONAL THERAP OF ANTIBIOTICS

P2#M2)B!@?T!)SP2#M2)B!@?T!)S

P2#M2)BD!@2M!)SP2#M2)BD!@2M!)S

ANTIBIOTICS HOST


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)2#2)T?#!ST!))2#2)T?#!ST!)

B/ 2@T!,!BT!)SB/ 2@T!,!BT!)S

HOST ASPECTS

BIOCHEMICAL !

PHSIOLOGICAL !PATHOLOGICAL

CONDITIONS


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DEFINITION OF RATIONAL USE OFDEFINITION OF RATIONAL USE OF

ANTIBIOTICS "#HO$ANTIBIOTICS "#HO$

P#BP?# !@D!)2T!B@P#BP?# !@D!)2T!B@

P#BP?# D#U=P#BP?# D#U=

P#BP?# DBS2=?P#BP?# DBS2=?

S? MB@!TB#!@=S? MB@!TB#!@=


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#2T!B@2L US? B/ 2,#2T!B@2L US? B/ 2,

P#B)?DU#?SP#B)?DU#?S

ST?PS TB P#B)?DU#?SST?PS TB P#B)?DU#?S

Define t%e &'tient &ro()e*s s&ecif+ t%e

t%er'&e,tic o(-ectivesVerif+ t%e s,it'()e of +o,r &erson')

tre't*ent

St'rt t%e tre't*ent

Give infor*'tion. instr,ction 'n/ 0'rnin1

Monitorin1 'n/ sto& tre't*ent

C)inic') /i'1nosis

I/entific'tion. sensitivit+ test of('cteri'

P%'r*'co/+n'*ics

P%'r*'co2inetics

Host f'ctors


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RATIONAL USE OF ANTIBIOTICSRATIONAL USE OF ANTIBIOTICS

THERAPYTHERAPY ?#2D!)2T!@=?#2D!)2T!@=

M.BM.B

D?/!@!T!E? T?#2PFD?/!@!T!E? T?#2PF

?MP!#!) T?#2PF?MP!#!) T?#2PF

ROH!"A#ISROH!"A#IS

IN NON S$R%ICA"NON S$R%ICA" CONDITIONS

IN S$R%ICA"S$R%ICA" CONDITIONS

R&'&NTION IN HI%HR&'&NTION IN HI%H

S$SC&TIBI"IT! TOS$SC&TIBI"IT! TO

%&T IN(&CTION%&T IN(&CTION


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DEFINITIVE THERAPDEFINITIVE THERAP

!t is the most effective least to8icity!t is the most effective least to8icityand the narro$est selectionand the narro$est selection

,ased on %,ased on %

G identification of 3acteriaG identification of 3acteria

G sensitivity testG sensitivity test

G interpretation in the content of theG interpretation in the content of the

overall clinical pict"reoverall clinical pict"re

G the 2, of choice directed to M.BG the 2, of choice directed to M.B


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EMPIRIC AB THERAPEMPIRIC AB THERAP

=iving 2, directly $itho"t identification=iving 2, directly $itho"t identification

and sensitivity test of 3acteria 3"tHHand sensitivity test of 3acteria 3"tHHobtaining specimen for lab. analysisobtaining specimen for lab. analysisbefore giving AB.beforegiving AB.

?mpiric 2, therapy 3ased on local?mpiric 2, therapy 3ased on local

epidemiological data %epidemiological data %I Ahat is the pathogen M.B potentiallyAhat is the pathogen M.B potentially

infectedinfected

I 2, given 3ased on s"scepti3ility pattern2, given 3ased on s"scepti3ility patternI !nitiated after o3taining specimen!nitiated after o3taining specimen

I Started $ith 2M com3ination or singleStarted $ith 2M com3ination or single,S2,,S2,


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SELECTING AB IN EMPIRIC THERAPSELECTING AB IN EMPIRIC THERAP

The site of infectionThe site of infectionThere are 3arriers inside the 3ody %There are 3arriers inside the 3ody %

3rain prostate 3one3rain prostate 3one

Bther % foreign 3odiesBther % foreign 3odieslocal factorslocal factors

Patients history %Patients history %


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INDICATION IN EMPIRIC THERAPINDICATION IN EMPIRIC THERAP

!nfection of "n-no$n origin!nfection of "n-no$n origin

@e"tropenic patients@e"tropenic patients

)haracteristic symptoms of meningitis)haracteristic symptoms of meningitis

M!SUS? of 2, %M!SUS? of 2, %Treatment of "ntreata3le infectionTreatment of "ntreata3le infection

Therapy of fever of "n-no$n originTherapy of fever of "n-no$n origin

!mproper dosage!mproper dosage

!nappropiate reliance on 2, alone!nappropiate reliance on 2, alone

Lac- of ade"ate 3acterial informationLac- of ade"ate 3acterial information


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STRATEGIC FOR EMPIRIC THERAPSTRATEGIC FOR EMPIRIC THERAP

?mpiric therapy %?mpiric therapy %

)overage 3y a com3ination of anti3iotics s"ch as)overage 3y a com3ination of anti3iotics s"ch as

)lindamycin pl"s gentamycin)lindamycin pl"s gentamycin

?ffective against gram positive gram negatives and anaero3es?ffective against gram positive gram negatives and anaero3es

BrBr 2 single 3road spectr"m 2,2 single 3road spectr"m 2,

S"ch as imipenem7cilastatinS"ch as imipenem7cilastatin

#eceive c"lt"re report#eceive c"lt"re report

Aith sensitivitiesAith sensitivities

!f gram positive only!f gram positive only if mi8edif mi8ed

)ontin"e gram pos.)ontin"e gram pos. contin"e therapycontin"e therapy

)overage discontin"e)overage discontin"e as initiated as initiated

=ram neg. and anaero3ic=ram neg. and anaero3ic

)overage)overage

!f gram negative only!f gram negative only !f anaero3ic only!f anaero3ic only

)ontin"e gram neg.)ontin"e gram neg. contin"e anaero3ic coveragecontin"e anaero3ic coverage

coverage discontin"ecoverage discontin"e discontin"e gram positivediscontin"e gram positive

=ram pos. and anaero3ic=ram pos. and anaero3ic and gram negative coverageand gram negative coverage

)overage)overage

C%'&ter 34. Fi153456 Li&&incott7se/53n/


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P#BPFL2C!SP#BPFL2C!S

SU#=!)2LSU#=!)2L

1.1. )ontaminated op.)ontaminated op.

'.'. )lean )lean

contaminated opcontaminated op

4.4. Selected opSelected op maymay

s"ffers"ffer

postIop.infectionpostIop.infection

NON SURGICAL

PREVENT :

65 Stre&tococc') infection in

&'tient 0it% ' %istor+ of

RHD

35 In &re8/ent') e9tr'ction

0%o %'ve i*&)'nte/

&rost%etic /evices

5 TB;*enin1itis in c)osecont'ct in/ivi/,')


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D!S2@E2@T2=?S TB P#BPFL2)T!) 2,D!S2@E2@T2=?S TB P#BPFL2)T!) 2,

1.1. To8ic7allergic reactionTo8ic7allergic reaction

'.'. S"perinfection $ith more resistantS"perinfection $ith more resistant

floraflora

4.4. The infection may 3e temporarilyThe infection may 3e temporarilymas-edmas-ed

:.:. ?cology of the hospital flora may 3e?cology of the hospital flora may 3e

alteredaltered


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)BMMB@ )2US?S B/ /2!LU#? B/ 2,)BMMB@ )2US?S B/ /2!LU#? B/ 2,T?#2PFT?#2PF

D#U=S %D#U=S % inappropriate dr"ginappropriate dr"ginade"ate doseinade"ate dose

improper ro"te of administrationimproper ro"te of administration

accelerated inactivationaccelerated inactivation

poor penetrationpoor penetration

BST %BST % poor host defencepoor host defence

"ndrained p"s"ndrained p"s

retained infected foreign 3odiesretained infected foreign 3odies

cr"sta7necrotic tiss"escr"sta7necrotic tiss"es


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)ont.)ont.

I PathogenI Pathogen dr"g resistencedr"g resistence

s"perinfections"perinfection

d"al infection initiallyd"al infection initially

I La3oratory %I La3oratory %

erroneo"s report of s"scepti3leerroneo"s report of s"scepti3le

pathogenpathogen


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2, )BM,!@2T!B@2, )BM,!@2T!B@

Synergisme (4+ %Synergisme (4+ %

1+ ,loc-ade of se"ential steps in1+ ,loc-ade of se"ential steps in

a meta3olit se"encea meta3olit se"ence

I Trimethoprim I s"lfametho8a9olI Trimethoprim I s"lfametho8a9ol

'+ !nhi3ition of en9ymatic inactivation'+ !nhi3ition of en9ymatic inactivation

I 2mo8ycillin I clav"lanatI 2mo8ycillin I clav"lanat

4+ ?nhancement I 2minoglycosides4+ ?nhancement I 2minoglycosides

I Penicillins I 2minoglycosidesI Penicillins I 2minoglycosides


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2ntagonism ('+ %2ntagonism ('+ %

1. !nhi3ition of cidal activity 3y static1. !nhi3ition of cidal activity 3y staticagentagent

I Tetracyclines ,etalactam 2,I Tetracyclines ,etalactam 2,

'. !nd"ction of en9ymatic inactivation'. !nd"ction of en9ymatic inactivation

I 2mpicillin I PiperacillinI 2mpicillin I Piperacillin


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)L!@!)2L !@D!)2T!B@ B/ 2,)L!@!)2L !@D!)2T!B@ B/ 2,

)BM,!@2T!B@ %)BM,!@2T!B@ %

Mi8ed infectionMi8ed infection

Synergism effectSynergism effect #is- of developing resistant#is- of developing resistant

organism organism

!ncrease 2, coverage or!ncrease 2, coverage or !nfection of "n-no$n origin!nfection of "n-no$n origin


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D!S2DE2@T2=?S B/ 2, )BM,!@2T!B@D!S2DE2@T2=?S B/ 2, )BM,!@2T!B@

I !ncrease ris- of to8icityI !ncrease ris- of to8icityI !ncrease MD#IpathogensI !ncrease MD#Ipathogens

I !ncrease costI !ncrease cost

I !ncrease antagonism (3acteriostaticI !ncrease antagonism (3acteriostatic

3actericide+ 3actericide+


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27. rational use of antibiotics

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