September 7, 2011 Antimicrobial Stewardship
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Transcript of 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
$odi#cation of antimicrobial therap% once the cause ofinfection is identi#ed! Therap% ma% also be
discontinued if the diagnosis of infection becomesunli&el%!1
'ocus on de-escalation of antibiotic therap% with thegoal of minimiing resistance and to(icit%) andimproving cost-e*ectiveness!2)+1. Kollef MH. Drugs. 2003;63:2157–2168.
2. Kollef MH. Crit Care Med. 2001;29:1473–1475.3. Evans RS et al. N Engl J Med. 1998;338:232–238.
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Enterococcus S. aureus
K lebsiella spp. Acinetobacter P. aeruginosa Enterobacter spp!
Boucher ,) et al) lin Infect "is 2../0:1-12
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Antimicrobial stewardship involves the optimalselection, dose and duration of an antibioticresulting in the cure or prevention of infection
with minimal unintended conse3uences to thepatient including emergence of resistance)adverse drug events) and cost!
"ellit T,) et al! I" 2..40:15/-44),and 6) et al! ,ospital 7harmacist 2..011:5/-
87as&ovat% A) et al I9AA 2..5025:1-1.
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Ult!ate "oal s !#$ove% #atent &a$e an%
'ealt'&a$e o(t&o!es
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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
25
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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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+.
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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
1. Infect Control Hosp Epidemiol . 2010; 31
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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
1. Infect Control Hosp Epidemiol . 2010; 31
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Initial #pisoes $ecommeneTreatment
$ild or moderate $etronidaole 5.. mg7< TI" for 1.-1 da%s
Severe ?ancom%cin 125 mg7< JI" for 1.-1 da%s
Severe) complicated ?ancom%cin 5.. mg7< JI" plusmetronidaole 5.. mgI? J,
1. Infect Control Hosp Epidemiol . 2010; 31
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$ecurrentIn%ection
$ecommeneTreatment
'irst recurrence Same as initialepisode
Second recurrence ?ancom%cin taperedand>or pulsed
1. Infect Control Hosp Epidemiol . 2010; 31
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7rospective) randomied) double-blind) placebo- controlled trial
15. patients completed stud% Strati#ed patients: mild or severe
ompared metronidaole 25. mg 7<JI" to vancom%cin 125 mg 7< JI"for 1. da%s
3. Clinic Infect Dis. 2007; 45:3027.
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3. Clinic Infect Dis. 2007; 45:3027.
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Treatment failures with bothmetronidaole and vancom%cin
Increasing rates of recurrence withboth vancom%cin and metronidaole
=is& of ?=E coloniation with bothagents
A"=s with current treatmentsespeciall%) metronidaole
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$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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