Antibiotic Smart Use

7/21/2019 Antibiotic Smart Use

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คณะแพทยศาสตร ศ ร ราชพยาบาลมหาวทยาล ยมห ดล

.

Pornpan Koomanachai

Division of Infectious diseases and Tropical MedicineDepartment of Medicine, Faculty of Medicine SirirajHospital




AS

A major threat to pu!lic health

ป ญหาหล กทางสาธารณสข




ASAnti!iotics

Commonly used in ambulatory care facility

(ใช บ อย) Antibiotics can be purchased without

prescriptions (ซ อเองได )

A systematic revie" and meta#analysis

Antibiotic prescribing in primary care Prescribing an antibiotic in primary care for

a respiratory or urinary infection developbacterial resistance to that antibiotic

Costelloe C et al.BMJ 2010;340:c2096




AS

URI and acute diarrhea: common self-limiting(การต ดเช อทางเด นหายใจส วนต นและท องร วง

เฉ ยบพล น)

The prevalence of group A streptococci !A"# inadults with sore throat attending "irira$ %ospital

&'() to **'+)

,o compelling data on antibiotic treatment ofpatients with URI other than !A" are benecial

Asawapo.ee , et al' / Infect 0is Antimicrob Agents *(1+2 3: *+*-4 Treebupachatsa.ul P et al' / 5ed Assoc Thai 677821(1#:**&1-18




AS

In healthy individuals with acute diarrhea almost always self-limited2 หายได !ง$$$$

"tandard guidelines การใช ยาต

านจลช พต

อง! "

อบ

งช

ส #า$ % $ อ empiric antibiotic therapy is recommended

only for invasive or in9ammatory diarrhea

especially in special hosts withimmunocompromised conditions

non-in9ammatory diarrhea with moderate orsevere dehydration such as cholera




AS

ส "า# กงา#คณะกรรมการ!าหารและยาส$าบ #ว% ยระบบสาธารณสข

!งค การ!#าม ย&ลก




AS

*'เ& าห!าย $ อ ลดการใช ยา&' ช วนะอย างพร # าเพร

อใน

3

(ร$ท พบบ อย- (ร$ต ดเช อทางเด นหายใจส วนบน

- (ร$ท องร วงเฉ ยบพล น- แ)ลเล อดออก

6' A"U เ& *น($รงการท หว ง)ลให เก ดการเ&ล ยนแ&ลงทางพ+ต กรร!3' A"U เห!าะก บส,านพยาบาลท การส งใช ยา&' ช วนะ!ากเก นจ #าเ& *น!

สาเหต!าจาก- $วา!ร- หรอ$วา!เช อท $าดเ$ล อน"องบ$ลากรทาง การ

แพทย .

- แรงกดด นหร อ$วา!$าดหว ง"อง)- & วย+' A"U ต งอย- บนแนว$ ดท ว าการเ&ล ยนพ+ต กรร!เร !จาก$วา!ร- แต $วา!ร- อย างเด ยวไ! เพ ยงพอในการเ&ล ยนพ+ต กรร!




P%I&'IP() *F A&TI+I*TI' S)D

'ommon Inappropriate se of Anti!ioticsC%"I,! A,TI;ITIC T%<RAP= ;A"<0 "><>= ,

"P<CTRU5 เล อกใช ยา(ดยด-แต $วา!สา!าร,ในการ$รอบ$ล!เช อPR>,!<0 U"< ? I@ A,TI;ITIC" ใช ยาฉ ดเ& *นเวลานาน

U"< ? C5;I,ATI, T%<RAP= T PR<@<,T AT;

R<"I"TA,C< ใช ยา!ากกว า

* "นานเพราะเช อว าจะ& องก นการด อยา@<RR<>IA,C< , 5ICR;I>!= R<"U>T" เล อกใช ยาตา!)ลเพาะเช อเพ ยงอย างเด ยวU"< ? AT; ?R P<R"I"T<,T ?<@<R" ใช ยาต านจลช พเพราะไ" ไ!

ลดลงI,A0<UAT< "UR!ICA> T%<RAP= A,0 >ACB ? ,,-AT;

T%<RAP= ? I,?<CTI, "าดการร ก/าร ว!อ น0ท ส #า$ %PR>,!<0 AT; T%<RAP= R PRP%=>AI" ใช ยานานเก น$วา!จ

#าเ& *น




'H**SI& AT+ +AS)D S*()(- *&SP)'T%M

Anti!iotic tissue penetrationระด บยา'#ต "าแห# (งท ) (ม )การต ดช * !AT; eDective in-vitroE unable to reach the site of infection

rinary tract infections. same patho/ens !ut$ drugs for catheter-associated bacteriuria and cystitis

diDer from those used for pyelonephritisE prostatitisEor epididymitis

?luoroFyuinolones: high concentration in the prostate

GGmoHi9oHacin2 not achieve signicant urinaryconcentration




'H**SI& AT+ +AS)D S*()(- *&SP)'T%M

Anti!iotic tissue penetration

ระด บยา'#ต "าแห# (งท ) (ม )การต ดช * !AT; eDective2in-vitroE unable to reach the site of

infection

'hronic infections # decrease vascularpermea!ility

chronic pyelonephritisE chronic prostatitisE chronic

osteomyelitis

Implanted forei/n materials

biolm- slimeglycocalyH on plasticmetal surfaces




'H**SI& AT+ +AS)D S*()(- *&SP)'T%M

Anti!iotic tissue penetrationระด บยา'#ต "าแห# (งท ) (ม )การต ดช * !

AT; eDective2in-vitroE unable to reach the site of infection

Special !arrier or a!scesses ocularE 9uidE C"?E abscess cavityE prostateE bone

aminoglycosides2 less active in the low-oHygenE low-

p%E and high-protein environment of abscessesGG drainage of abscesses to enhance antimicrobial

eJcacy




'H**SI& AT+ +AS)D S*()(- *&SP)'T%M

Anti!iotic tissue penetrationระด บยา'#ต "าแห# (งท ) (ม )การต ดช * !

AT; eDective2in-vitroE unable to reach the site of

infection

Poor Tissue 'oncentration of AT+

Ti/ecycline rinary tract 0(un/, +lood1

Daptomycin (un/

2st# and 3nd#/en ceph4 !lood#!rain !arrier

Macrolides !lood#!rain !arrier




'H**SI& AT+ +AS)D S*()(- *&SP)'T%M

+actericidal agents cause

death and disruption of the

bacteria

0isruption of cell wallo ß-lactams

cell membrane

o daptomycin

;acterial 0,A

o 9uoroFuinolones

+acteriostatic agents

inhibit bacterialreplication

without .illing theorganis

inhibiting proteinsynthesis

o

sulfonamideso tetracyclines

o macrolides

+ectericidal vs +acteriostatic therapy

การ!!ก+ทธ ข!งยา'#การย บย งการต ดช * !

G;actericidal agents are in the serious infections to

achieve rapidcure such as endocarditis and menin/itis



คณะแพทยศาสตร ศ ร ราชพยาบาลมหาวทยาล ยมห ดลP%*(*&)D S) *F I5

A&TI+I*TI'S

I5#to#P* s"itch therapyปล ) (ย#ยา, ) ดป - #ยาร บประทา#+arrier for intravenous#to#oral 0I5#to#P*1

# สยไม (ด )ก (า.แก ยาก$$$$

K Physicians are creatures of habitE and oldhabits die hardLM Burke A. Cuna! M" #$n%ectious "isease "ivision!

&intro'-(niversit) *os'ital! Mineola! +, 1101! (A/

I@ therapy: rst used for serious systemic infections 5any infections susceptible to I@ AT;

I@ therapy: the preferred mode of AT;administration




6hy$ *ral anti!iotic therapy

Advanta/es (ข !ด ))

>ower AT; acFuisition cost

,o I@ AT; administration

costs Rapid gastrointestinal

absorption N* h# even incritically ill patients

<liminates I@-line infections

0ecreased length ofhospital stay

<arlier discharge

Disadvanta/es (ข !ด !ย)

"hould not be used inthose with impairedgastrointestinal absorption

Patient in shoc.E begintherapy intravenously

Increased ecologicalhaOard

oral agent with poorbioavailability potentiate

coloniOation#

Cunha BA. Antibiotic essentials. 5th edition. 2006

Cunha BA. Drugs Today 2001;37311!"#uintiliani $% &ightingale C'. (n)ect Dis Clin *ractice 1""+;3,-ul/161!7




'ost#e7ectiveness$ I5#to#*ral S"itchtherapy

The study ofcost#e7ectiveness 'ost savin/8reduction

TusconE AE U"AE 677&by Patanwala A<'

from Q11,479 to Q8923 per a treatment

course"witOerlandE 6773

von !unten @'

++ to (6 <uros per a treatment course

;uDaloE ,=E U"AE 6776by Paladino /A'

from Q8E*+4 to Q4E684 per a treatmentgroup

%artfordE CTE U"AE *((3by ,ightingale C%'

Q*47E777 - Q647E777 per year

@ancouverE *((+by /ewesson P'

QC 6*E4 77 per year

,etherlandE *((6by /an.negt

,! 8&E*87 per patient per day




6hen$ *ral anti!iotic therapy

*ral a!sorption in the critically ill

- ral AT;with goodeHcellent bioavailability

rapidlywell

absorbed achieve bloodtarget tissuelevels

GGeHcept septic shoc.

- Per oral ∼ per nasogastric tube or perpercutaneous

enteroscopic gastroscopy tube

คณะแพทยศาสตรศรราชพยาบาล




%e9uirements of an oral AT+

Anti!iotic Factorsป %% ยด า#ยาต า#%ลช )พ

high degree of activityagainstpresumed.nownpathogens

high bioavailability

low resistancepotential

well tolerated with agood safety prole

Host Factorsป %% ยด า#/0 ป ( วย

patient able tosuJciently absorb anoral antibiotic

avoid in patients withimpairedgastrointestinal

absorption




คณะแพทยศาสตร ศ ร ราชพยาบาลมหาวทยาล ยมห ดลDu:e niversity Medical 'entre

'riteria

ต ว!ย (างAbsent of infectious indications reFuiring parenteralAT;

• febrile neutropenia• signicantly immunocompromised• meningitis• osteomyelitis

• endocarditis• septic shoc.• disseminated viral infections such as %"@

Moie %ro elekis an 5oul. J *os' $n%ect 2001; 4: 249 J $n%ect 199; 37#su''l 1/:3-9




คณะแพทยศาสตร ศ ร ราชพยาบาลมหาวทยาล ยมห ดลDu:e niversity Medical 'entre

'riteria Absent of infectious indications reFuiring parenteral AT;

Infection is not presently serious or life-threatening

Improved of signs or symptoms of infection

Afebrile or has consistent improvement in fever 6+ hrs

S;C count is normaliOing

,ormal gastrointestinal absorption of drugs and the

patient is able to receive enteral therapy

Moie %ro elekis an 5oul. J *os' $n%ect 2001; 4: 249 J $n%ect 199; 37#su''l 1/:3-9





What are types of IV-to-oral switch?

Stream#linin/; converting from broad-spectrum

AT; to single agent with narrow spectrum

Se9uential; converting I@ to oral agents with

same chemical

S"itch; converting I@ to oral agents with identical

potency

Step#do"n; converting I@ to oral agents withreduced

potency ศาสตราจารยแพทยหญงนลน





Bioavailability of oral antibiotics

< =>? =@#=>? @#=? B @?

'ephaleCin 'lindamycin AmoCicillin AmoCycillin8'lavulanic

acid

'otrimoCaole DoCycycline Ampicillin8

Sul!actam

'larithromyci

n(evoEoCacin *EoCacin 'iproEoCacin DicloCacillin

(ineolid Tetracycline 'efditorenpivoCil

Metronidaole 'eCime

'efti!uten

'efuroCimeaCetil

'efpodoCimeproCitil

KeEeC

Meiact

'efspan

5antin

Ginacef

'edaC





S) *F '*M+I&ATI*& TH)%AP-

Monotherapy. preferred overcom!ination

therapy - reduces the ris. of2 drug interactions

medication errors missed doses and side eDects

usually less eHpensive than combination therapy

'om!ination Therapy drug synergy

eHtended spectrum





'om!ination Therapy; Syner/y

β#lactams and amino/lycosides eChi!itssyner/ism for treatment of endocarditis

caused !y.

8nterococcus spp'

A viridans group streptococci ta')lococcus aureus

Penicllin and clindamycin; clinicalsyner/ism for

treatment of S. pyogenes infection





'om!ination vs monotherapy

P%*ข !ม0ลส# บส##

"ynergistic eDect in

vitro !ood outcome in

severely ill

"eptic shoc.Eneutropenia#

%igher rate of

microbiological cure

'*&ข !ม0ลค ดค า#

%igher rates of resistance

isolates %igher rates of side

eDects

>ac. of the power to

showed the consistent ofgood outcome

,o top level of gradingevidence

C$" 2011;3 #u''l 2/:33

$CAAC 2011! Cicao $"A 2011 a n rancisco! (A





'*M+I&ATI*& TH)%AP- T* P%)5)&T AT+%)SISTA&')

Anti!iotic com!inations that

prevent resistance

*# Anti-pseudomonal penicillin aminoglycoside

6# Rifampin other T; drugs

I,%E ethambutolEpyraOinamide#

3# 4-9ucytosine amphotericin ;

+# Anti-retroviral drugs in %I@AI0" therapy





'ommonly used anti!iotic com!inationsthat do not prevent resistance

ยาท ) (# ยม'ช 'ห หลายข#า#แต ( '#ความป - #%ร งไม ( ได ป !งก #ช * !ด * !ยา

*# T5P-"5

6# CeftaOidime in combination with any otherAT;

3# Cipro9oHacin in combination with any otherAT;

+# Imipenem in combination with any other AT;

4# 5ost other AT; combinations

'*M+I&ATI*& TH)%AP- T* P%)5)&T AT+%)SISTA&')

คณะแพทยศาสตรศ รราชพยาบาล



คณะแพทยศาสตร ศร ราชพยาบาลมหาวทยาล ยมห ดล

*5)%%)(IA&') *& MI'%*+I*(*-%)S(TS

$n vitro data do not diDerentiate between

coloniOers and pathogens determine whether the organism is a pathogen or a

coloniOer

coloniOation should not be treated

$n vitro data do not necessarily translate into

in vivo eJcacy VsensitiveV or VresistantV to a given antibiotic in-vitro

do not necessarily re9ect in-vivo activity

คณะแพทยศาสตรศ ร ราชพยาบาล



ณ ร รรมหาวทยาล ยมห ดล*5)%%)(IA&') *& MI'%*+I*(*-

%)S(TS

$n vitro susceptibility testing is dependent onthe microbeE methodologyE and AT;

concentration2 assumes the isolate was

recovered from bloodE and is being eHposed to

serum concentrations Usually higher AT; concentrations than in serum:

bladderE urine

>ower AT; concentrations than in serum: C"?E ocular

$n vitro data may be misleading for non-bloodstreaminfections

คณะแพทยศาสตรศ ร ราชพยาบาล



มหาวทยาล ยมห ดล

S) *F A&TI+I*TI'S F*% P)%SIST)&TF)5)%

The most common error in the managementof

persistent fevers

Changingadding additional antibiotics

insteadof determining the cause ปร บยาไม (ม )การว# %, ย

5ore important to reassess the patient

Causes of prolonged fevers include ,on-infectious medical disorders e'g'E "><#

0rug fever

In-vitro susceptibility but inactive in-vivo

คณะแพทยศาสตร ศ ร ราชพยาบาล



มหาวทยาล ยมห ดลS) *F A&TI+I*TI'S F*% P)%SIST)&T

F)5)%

InadeFuate spectrum

InadeFuate AT; bloodand

tissue levels

Undrained abscessE

?oreign body-relatedinfection

"pecial barrier C"?

rgan hypoperfusion

diminished blood supply

- chronic osteomyelitis in

diabetics#

AT; inactivationE AT;

antagonism#

?ungal superinfection

Treating coloniOation

AT;-unresponsive

infectious

diseases2 viral infections

Undiagnosed causes of

leu.ocytosis

>ow-grade fevers shouldnot be treated with

prolonged courses of AT;





&*&#AT+ TH)%AP- *F I&F)'TI*&

*perative draina/e or d!ridement !et rid of the high organism burden abscesses#

'orticosteroid; conjunction "ith AT+ therapy ;acterial meningitis

Tuberculous meningitis

<neuoc)stis 'neuonia in AI0"

Temporary discontinuation or dose reductionof

immunosuppressive a/ents

C5@ disease in organ transplant recipients or patientswith

rheumatologic disorders

Pro!ioticsancet $n%ect "is 2004;4(3):139-143

+ 8nl J Me 2004;351(17):1741-1751+ 8nl J Me 1990;323#21/:1444-140

Anaero=e 2009;15(6):274-280




มหาวทยาล ยมห ดลP%*(*&)D AT+ TH)%AP- *%

P%*PH-(AJIS

Duration of AT+ therapy Prolon/ed courses of AT+ therapy

Potential for adverse reactions

Problems with adherence

"election of AT;-resistant organisms

%igh cost





P%*PH-(AJIS

Potential for adverse reactionsDirect

Allergy

ToHicity

0rug-drug interaction

Therapeutic failure

Indirect

<Dects on commensal 9ora

W %uman Clostriiu i>cile in%ectionW Animal Increased chance of infection with

drug-resistant pathogens

<Dects on environmental 9ora





P%*PH-(AJIS

Duration of AT+ therapy <Hamples of optimal durationE shorter but

eDective course Uncomplicated UTI in women 3 days

Community-acFuired pneumonia 4 days

@entilator-associated pneumonia 1 days

GG not suJcient for the treatment of infections due

to <. aeruinosa or in immunocompromised patients <ndocarditisE osteomyelitisE +-8 wee.s

and intra-abdominal abscesses

Cocrane "ata=ase )st ?ev 200;#2/:C"00462

Clin $n%ect "is. 2003;37#6/:72-760 JAMA. 2003;290#19/:2-29





P%*PH-(AJIS

Duration of AT+ prophylaCis

Presur/ical AT+ prophylaCis To reduce the incidence of postoperative

surgical siteinfections

The AT; should cover the most li.elyorganisms and

be present in the tissues At the initial incision

Clin $n%ect "is. 2004;3#12/:1706-171





P%*PH-(AJIS

Duration of AT+ prophylaCis

Presur/ical AT+ prophylaCis AdeFuate serum concentrations during the

procedure A single dose of a cephalosporin such as

cefaOolin#

within * hour before the initial incision

Avoiding unnecessary broad-spectrum AT; 0uration2 should not eHceed 6+ hours

Clin $n%ect "is. 2004;3#12/:1706-171





'ase Study

#year#old man

?ever 1 w.s

>eft cervical lymphadenopathy 1w.s

,auseaE vomitingE and hiccup 1w.s

Seight loss 4.g8w.s

Chronic hepatitis C infection 3 yrs%epatomegaly with $aundice

Anemia





Di7erential dia/nosis

(ymphoma

T+8&ontu!erculous myco!acterium0&TM1

Infectious mononucleosis 0)+51

Solid tumor; CA nasopharynHE CAesophagusE

%epatoma

LHI5 pportunistic infection or lymphoma#

Histoplasmosis

C5@Cat scratch disease

%epatitis C





'ase Study

>#year#old man

,ecessary Investigations were performed ;lood smear

%C for bacteriaE mycobacteriaE fungus

>, biopsy

;5 aspiration and biopsy

CT2 ,asopharyHE thoraHE abdomen

%e was treated with ceftriaHone 6g ivE 0 for 3days'

?ever was still high and >?T hepatocellula rin$ury#

was worsening with anemiaE thrombocytopeniaE

leucopenia'

The AT; was changed to meropenem at day-3 of

ceftriaHone'

• ,o appropriate provisional diagnosis• Use AT; to treat prolonged fever

• Changed AT; without reassessment thepatient





;one marrow and >,: >ymphoma with

hemophagocytis Treatment - I@IgE 0eHamethasone I@ - clinical improved

Chemotherapy

The patient developed febrile neutropenia'

"eptic wor. up was performed and meropenem wasprescribed for 4 days and the fever was decreasingwhile

neutrophil was increasing from *47 to 167'

"putum culture grew A. =auannii on day-4 ofmeropenem then colistin was prescribedE continued

meropenem'

'ase Study

• Use AT; based on culture result to treat

coloniOation• Changed AT; without reassessment thepatient• AT; as a ris. of adverse eDect2 renal toHicitywithout

any benet





The patient still has low grade fever after & days

of

colistinE neutrophil was increasing from *47 to*E767' Cr

rising from *'6 - 3'6E sputum C" grew A.

=auannii

but resist to colistin' Clinical is similar topreviously but

this timeE no AT; was prescribed'

'ase Study

• Increasing adverse eDect2 renal toHicitywithout

any benet

คณะแพทยศาสตร ศ ร ราชพยาบาลมหาวทยาลยมหดล




Messa/es

6hat is the dama/eof inappropriateAT+

5orbidity X mortality

Adverse eDects

%igh cost-ineDectivesness

<mergence ofresistant

Ho" to /et

appropriate AT+

An accurate diagnosis

The need for AT;E which AT;

and timing of AT; RH Using the narrowest

spectrum

and shortest duration of RH

"witching to oral agents A"AP

0osing regimens of diDerentagents

%ost characteristics

,on-AT; interventions




Pornpan Koomanachai, MD

Antibiotic Smart Use

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