September 7, 2011 Antimicrobial Stewardship

8/18/2019 September 7, 2011 Antimicrobial Stewardship

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Building Stewardship:A Team Approach

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A Balancing Act

Appropriate initial antibiotic

while improving patient

outcomes and heathcare

Appropriate initial antibiotic

while improving patient

outcomes and heathcare

Unnecessary

antibiotics and adverse

patient outcomes and

increased cost

Unnecessary

antibiotics and adverse

patient outcomes and

increased cost


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Empiric

Initial administration of a broad-spectrum antibioticregimen that attempts to improve outcomes andminimie resistance!

"e#ned or Targeted

$odi#cation of antimicrobial therap% once the cause ofinfection is identi#ed! Therap% ma% also be

discontinued if the diagnosis of infection becomesunli&el%!1

'ocus on de-escalation of antibiotic therap% with thegoal of minimiing resistance and to(icit%) andimproving cost-e*ectiveness!2)+1. Kollef MH. Drugs. 2003;63:2157–2168.

2. Kollef MH. Crit Care Med. 2001;29:1473–1475.3. Evans RS et al. N Engl J Med. 1998;338:232–238.


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Enterococcus S. aureus

K lebsiella spp. Acinetobacter P. aeruginosa Enterobacter spp!

Boucher ,) et al) lin Infect "is 2../0:1-12


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Antimicrobial stewardship involves the optimalselection, dose and duration of an antibioticresulting in the cure or prevention of infection

with minimal unintended conse3uences to thepatient including emergence of resistance)adverse drug events) and cost!

"ellit T,) et al! I" 2..40:15/-44),and 6) et al! ,ospital 7harmacist 2..011:5/-

87as&ovat% A) et al I9AA 2..5025:1-1.

-

Ult!ate "oal s !#$ove% #atent &a$e an%

'ealt'&a$e o(t&o!es


7/724S!onsen )S* et al . +(ll ,H- 2004;82:92834


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7romoting optimal antimicrobial use=educing the transmission of infections


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Antimicrobial =esistance: 7atients andhospitals in 7eril

The linical onse3uences of

Antimicrobial =esistance Transmission ontrol to 7revent the

Spread of $"=


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Infectious DiseasesSpecialists

AntimicrobialAntimicrobialControlControl

Infection ControlAdministration

ClinicalPharmacists

Nursing

Surgical Infection!perts"Surgeons

#$ Personnel

M&$oolo"

Pulmonar%"

Intensi&ist


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7rospective audit with intervention and feedbac& 'ormular% restriction and preauthoriationSupplemental Strategies

Education) guidelines) clinical pathwa%s

"ose optimiation via 76-7"

"e-escalation>Streamlining

Antimicrobial order forms>order sets if 7


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7rospective audits%stem Stewardship

program


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Sentri4Safet%Surveillor Thera"ocomputeried ph%sician order entr%Benchmar&ing and local antimicrobials

point prevalence surve%s state ma%consider doing thisC

la$%"e /* et al. S($" nfe&t 2010;11:12531


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an&aste$ /,* et al. 'a$!a&ot'e$a# 2008;28


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Antimicrobial therap% of establishedinfection should be limited to D4 da%s)unless it is dicult to achieve ade3uate

source control Bowel inFuries due to penetrating) blunt)

or iatrogenic trauma repaired within 12 hand an% other intraoperativecontamination of the operative #eld b%enteric contents should be treated withantibiotics for G2 hours

a& of ev%en&e of nfe&tons n&l(%es* en" afe$le* 'ave no$!al

,+* an% tole$atn" an o$al %et.


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2+


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The members of the team have to #tthe personal available

Sta* ph%sician with I" interest 7T chair or committee member

,ospitalist with interest in I"

HonDI"-trained clinical pharmacist

Sta* pharmacists with certi#cation instewardshipC

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7erforming selected stewardshipactivities should be consideredsuccessful ,elping patients is the goal) not struggling

to follow guidelines at the e(pensive to asuccessful program for %our institution

@ines of authorit% and reporting are &e% Jualit% and Safet%

7T for assistance with 77 and protocolapproval

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hallenges faced b% ommunit% ,ospitals @ac& of sucient resources

7rivate I" or H< I" ph%sicians or those that do notwant to be involvedC

I" pharmacist

Ho e(tra sta* especiall% pharmac%C


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departments

when possible 2/


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+1


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7rovide descriptors of antimicrobial activit%pro#les

7rovide surrogate mar&ers to predict drug

activit% Integrate LbugM and LdrugM data

Host

PathogenAntimicrobial PK/PD


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N-lactams Lnot much happens until an ade3uate

proportion of 7B7 are occupiedM

Smaller doses) more fre3uentl% 7rolonged or continuous infusion

TimeO$I

Aminogl%cosides>'luoro3uinolones AP:$I

ma(>$I

"ose AH" $I matter ++


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+5


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Best representedb% TimeO$I

MIC


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Best representedb% ma(:$I ratio

ma(:$I ratioO-12 associatedwith clinicalsuccess


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"ose-fractionation e(periment with lomeQo(acin in an animalmodel

Same total dose given as di*erent regimens

.mg>&g 32h

.mg>&g 312h

2.mg>&g 38h

ontrol

@ode) et al! lin Inf "is 1//024:++


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?aries b% particular isolate of organism LSame drug) di*erent bugM

E(! iproQo(acin vs! Pseudomonas

Time

- on c en

t r at i on

AP>

$I $I$IG1 mcg>m@

$IR mcg>m@AP>$I

ipro-sensitive ipro-resistant


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Traditional pharmaco&inetic parameteralculated based on total serum

concentrations of drug


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Surrogate for AP of unbound drug atsite of infectionat receptor site

"oes not account for susceptibilit% of

organism"icult to measure in clinical practice

7rotein Binding Entr% into infected site Access to bacterial target

Assa%ed E*ective


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Dudley & Ambrose. Curr Opin Microbiol

2000!"#$#%#2$

andom pharmaco'inetics

and M(C values

)rom dataset

*lot results in

a probability chart

Calculate

pharmacodynamic

parameter

AUC M(C

AUC"M(C


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$onte arlo simulation

determine distribution of antimicrobial potenc%eg $I distributionC

determine distribution of antimicrobial

e(posureseg APsC

computer program randoml% selects parametersfrom each of the distributions 5..) 5...

iterations R patientsC and the probabilit%distribution of achieving the preset levelpharmacod%namic target attainment R speci#cAP:$I or TO$IC is computed

+icolau & Ambrose. Am , Med 200$$$$-A/"$!1$


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ram-positive anaerobic bacteria

E(oto(in producing

'ecal-oral transmission C. difcile infection "IC onset median 2-+

da%s

$ost common cause of infectiousdiarrhea 2.-+. of antibiotic-associated diarrhea

1. Infect Control Hosp Epidemiol . 2010; 31


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S(nens'ne et al. leve ln / Me%. 2006;73:18797.

(. )o!in A * B Production

leads to colon damage

+", pseudomembrane

1. Ingestion

of spores transmitted

from other patients

&ia the hands of healthcare

personnel and en&ironment

2. -ermination into

groing /&egetati&e0form

3. Altered loer intestine flora

/due to antimicrobial use0 allos

proliferation of

C. difficile in colon


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Age

,ospital duration

Antibiotic usage

hemotherap%

astrointestinal disruption



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Clinicale!nition

Supporti"e clinical ata

$ild or moderate ;B less than 15)... AH" Srless than 1!5 times premorbid

level

Severe ;B greater than 15)...


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"iscontinue an% potential causativeagent

Immediatel% initiate empiricaltreatment Severe or complicated

"ata of probiotic usage is inconclusive Hot recommended for primar% proph%la(is



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Initial #pisoes $ecommeneTreatment

$ild or moderate $etronidaole 5.. mg7< TI" for 1.-1 da%s

Severe ?ancom%cin 125 mg7< JI" for 1.-1 da%s

Severe) complicated ?ancom%cin 5.. mg7< JI" plusmetronidaole 5.. mgI? J,



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$ecurrentIn%ection

$ecommeneTreatment

'irst recurrence Same as initialepisode

Second recurrence ?ancom%cin taperedand>or pulsed



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7rospective) randomied) double-blind) placebo- controlled trial

15. patients completed stud% Strati#ed patients: mild or severe

ompared metronidaole 25. mg 7<JI" to vancom%cin 125 mg 7< JI"for 1. da%s

3. Clinic Infect Dis. 2007; 45:3027.


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3. Clinic Infect Dis. 2007; 45:3027.


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Treatment failures with bothmetronidaole and vancom%cin

Increasing rates of recurrence withboth vancom%cin and metronidaole

=is& of ?=E coloniation with bothagents

A"=s with current treatmentsespeciall%) metronidaole


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$acroc%cles) a new class of antibacterials for oraladministration

Bactericidal against C. difcile, with a 7AE of 8-1. hrs Inhibits =HA s%nthesis b% =HA pol%merases 'ecal concentration are 5... times the $I/. of C

difcile isolates 7reservation of the microbiota of the I tract

compared with vancom%cin $inimal s%stemic absorption measured in the ng>ml

range 'ood does increase s%stemic absorption but increased

serum concentration is HmlC

o(e * et al. 2009;53:22328$o%(&t ael f&% 2011


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NEJM 2.110 +8: 22-81


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Inclusion riteria:

Adult patients O 18 %!o!C with a diagnosis of C.difcile infection 7resence of diarrhea: a change in bowel habits) O +

unformed bowel movements in the 2-hour period beforerandomiation

C di. To(in A) B) or both in a stool specimen obtained hours before randomiation

E(clusion riteria: =eceived: oral bacitracin) fusidic acid) or rifa(imin

@ife-threatening of fulminant C. di infection) to(icmegacolon) previous e(posure to #da(omicin) ahistor% of ulcerative colitis or rohns disease) or O1 occurrence of C. difcile infection within +months before the start of the stud% were e(cluded


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linical ure: resolution of diarrhea withmaintenance of resolution for duration of therap%and no further =(

linical failure: persistence of diarrhea) need for

additional =() or both lobal cure: resolution of diarrhea without

recurrence linical recurrence: If subFects remained in stud%

and had a follow up assessment at da% +8-.) afterrandomiation the% were evaluated for recurrence!"e#ned as reappearance of diarrhea within wee&safter stopping stud% medication) U to(in assa%) andneed for treatment


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Subgroup MITT&iax

MITT'anco

P"alue

PP&iax

PP'anco

P"alu

e

Age V 85%ears

2.>1.+1/C

.>1+1+.!5C

.!.5 18>51/C

+1>1.++.C

.!.

Inpatient 2>1+81C .>1824C .!.5 1/>1.81C 2/>11128C .!15

Ho7revious

episode of"I

+.>2111C

52>2142C

.!.1 22>1451+C

1>1+22C

.!.2

HA71>BI>.24

18>5/24C

1>8421C

.!2 11>52C

1+>552C

.!/+

HonHA71>BI>.2

4

12>1141.C

+>1212C

G.!..1

>1.+ C 24>1.825!5C

G.!..1

oncurrent 1>1 5>/. 2C .!1. >58 1C 2.>85 .!.+(!e$Atotal n(!e$


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ommerciall% available test in the world to detect anddi*erentiate the epidemic strain of C. difcile .24>HA71>BIC!B;ith rapid and accurate identi#cation of epidemic strain)Infection ontrol professional can sta% ahead of potentialoutbrea& situation!Innovative multiple( design enables detection of C. difcile Infection "IC and .24>HA71>BI strain call-out in a singlecartridgeBepheids Wpert C. difcile>Epi is a real time 7= test that runs onthe eneWpert s%stem

BeneWpert s%stem is the #rst to full% automate and integrate allthe steps re3uired for 7=-based "HA testing: samplepreparation) "HA ampli#cation and detection


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;h% the changesK Better 767" data and &nowledge about

resistance mechanism especiall% ESB@s Z Amp;hat were the% based uponK

$ostl% 7") e(pert opinion and a few case series!,ow does the change impact treatmentK $a% use an% agent based on the observed $I

result and pts factors) carbapenem are not

alwa%s needed,ow does it impact reporting of ESB@K Susceptibilit% of cephalosporins should H


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4.


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Some ESB@ producing isolates are susceptible in-vitro

7oor outcomes in patients with infections due toESB@s cephs

Bacteria often have ESB@s and Amp-li&een%mes

Ho need for ESB@ testing or con#rmator% testwith new brea&points!

,ospitals using '"A-approved AST devices canutilie e(isting '"A interpretive brea&points

Either '"A or @SI susceptibilit% interpretivebrea&points are acceptable to accrediting bodies!


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Drug Susceptible

Interm $esistance

"oripene

m

Y 1 2 V

Ertapenem

Y .!25 .!5 V1

Imipenem Y 1 2 V

$eropenem

Y 1 2 V

42

@SI $eeting $inutes 9an 2../


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September 7, 2011 Antimicrobial Stewardship