The Leading-Edge of Effective Surgical Prophylaxis 2017/Antimicrobial Surgical...- 2-5% of...
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The Leading-Edge of Effective Surgical Prophylaxis Sheryl Zelenitsky Professor, College of Pharmacy University of Manitoba http://creativecommons.org/licenses/by-sa/4.0 (Wikimedia Commons)
Transcript of The Leading-Edge of Effective Surgical Prophylaxis 2017/Antimicrobial Surgical...- 2-5% of...
TheLeading-EdgeofEffectiveSurgicalProphylaxis
SherylZelenitskyProfessor,CollegeofPharmacy
UniversityofManitoba
http://creativecommons.org/licenses/by-sa/4.0(WikimediaCommons)
■ Ihavenocurrentorpastrela0onshipswithcommercialen00es,andwilldonatethecurrent$200speakinghonorariumtotheCSHPFounda0on.
■ Thisprogramlearningac0vityhasreceivednofinancialorin-kindsupportfromanycommercialorotherorganiza0on
Disclosures
AcknowledgementsDivnaCalic,PhDcandidate
ChrisLawson,BSc(Pharm)
RyanLillico,PhDcandidate
Dr.TedLakowski,Professor
Dr.G.Zhanel,Professor
Dr.RakeshAurora,CardiacSurgery
Dr.RobAriano,Pharmacy
Dr.HilaryGrocoQ,Anesthesiology
http://cibinel.com/project/apotex-centre/
https://markosun.files.wordpress.com/2015/05/aerialspov22.jpg
Outline
1. Surgicalsiteinfec0ons(SSIs)andan0microbialprophylaxis(AP)
2. Limita0onsofgold-standardtrials,meta-analyses&clinicalprac0ceguidelines
3. Whatis“effec0ve”AP?Studiesincolorectalandcardiacsurgery
4. Howtoop0mizeAPforpa0entsintheclinicalse\ng?
LearningObjective
1. Tolearnhowan0microbialpharmacodynamicscontributetoeffec0vesurgicalprophylaxis;
2. Toiden0fytheprimaryvariablesinassessingan0microbialprophylaxis.
- 2-5%ofsurgeries
- ↑hospitalstay7-10d,re-admission5X
- ↑mortality2-3X
- $350,000-$1millionannually
SSIhealthcareburden
KnoopKJ,StackLB,StorrowAB,ThurmanR.TheAtlasofEmergencyMedicine,4e;2016http://accessmedicine.mhmedical.com/ViewLarge.aspx?figid=125437734,AccessedFeb19,2017
https://www.swchildrens.org/Pages/health-safety/health-library/library-detail.aspx?docId=%7B0A696E96-7165-456D-AAAA-D8E2A9851EA5%7D,AccessedFeb19,2017
- 50%ofSSIsarepreventable
TableII.6.7(WHO:PatientSafety:GuidelinesforSafeSurgery2009)
ü modifiablepa0entrisk-factors
ü skinprepara0on,ORinfec0oncontrol,surgicaltechnique
ü thermoregula0on,glucosecontrol,O2supplementa0on
SSIprevention
Pa0entrisk-factors:• obesity• malnutri0on• smoking• diabetes• ISmeds• coloniza0on• remoteinfec0on
Surgeryrisk-factors:• OR/surgicalcontamina0on• typeofsurgery• foreigndevice• drains• dura0onofsurgery
ü an0microbialprophylaxis
- reducebacterialburdenatincisionsiteandpreventSSI
- avoidSSI-associatedmorbidity,mortality&costs
- minimizecollateralresistance(eg,MRSA,ESBL,VRE)
- avoidan0microbial-relatedadverseeffects(eg,C.difficile)
GoalsofAPareto…
? selec0ngan0microbial
? selec0ngdose
? 0mingpre-opdose(within1h)
? re-dosingduringsurgery(every2t½’s)
? con0nuingajersurgery(none,<24hor48hforcardiacsurgery)
KeyAPdecisionsare…
APclinicalpracticeguidelines(CPGs)
2013
Limitationsofgold-standardtrials,meta-analyses&CPGs
- heterogeneouspa0ents… age,weight,Clcr,co-morbidi0es
- variablesurgeries… skinprep,ORinfec0oncontrol,dura0onofsurgery
- diverseSSIpathogens… hostnormalflora,localpathogendistribu0ons
- variousan0microbials… spectrumofac0vity,resistancerates,PKs
What is “effective” AP?
APforcolorectalsurgery…
Single-dose was more effective than multiple-dose gentamicin.
Incision conc
AUCsurg
Closure conc
Single-dose was more effective than multiple-dose gentamicin.
Gentamicin closure conc was strongest risk-factor for SSI.
Critical threshold = 1.6 mg/L
Gentamicin closure conc was strongest risk-factor for SSI.
APforcardiacsurgery…
Image:BaronS(2013).CardiovascularTherapeutics14:214-239.
n=55,40inPDanalysis69%male65±10y(36–82y)
90±17kgClcr74±16mL/min
⇒ SSIs at 30 days
X
X
X Incision conc
Closure conc
Istherecommendedcefazolinprophylaxisadequateincardiacsurgery?
₋ sex
₋ age
₋ weight
₋ BMI
₋ smoker
₋ Clcr
₋ diabetes
₋ Charlsonindex
₋ priorcardiacsurgery
₋ antibiotics<1month
₋ hospitalized<1month
₋ CABG,valvesurgery
₋ #grafts
₋ albumin
₋ glucose
₋ fluidbalance
₋ bloodreplacement
₋ CPBduration
₋ surgeryduration
₋ complications
₋ hospitalstay
₋ pre-opAPonly
₋ timingofpre-opAP
₋ cefazolindose
₋ totalcefazolindose
₋ cefazolinclosureconc
₋ cefazolinminconc
Cefazolin closure conc & duration of surgery were associated with SSI.
Zelenitskyetal.IDWeek2016,NewOrleans,NO.
Variable OR 95%CI p-value Cefazolinclosureconc(per10%decrease) 1.36 1.02-1.82 0.038
Durationofsurgery(per1hincrease) 2.94 1.13-7.64 0.027
AreaundertheROCcurve(95%CI)=0.789(0.583-0.996)Hosmer-Lemeshowp-value=0.21
T50 3.9 h
T25
T75
Critical threshold = 104 mg/L
₋ sex
₋ age
₋ weight
₋ BMI
₋ smoker
₋ Clcr
₋ diabetes
₋ Charlsonindex
₋ priorcardiacsurgery
₋ antibiotics<1month
₋ hospitalized<1month
₋ CABG,valvesurgery
₋ #grafts
₋ albumin
₋ glucose
₋ fluidbalance
₋ bloodreplacement
₋ CPBduration
₋ surgeryduration
₋ complications
₋ hospitalstay
₋ pre-opAPonly
₋ timingofpre-opAP
₋ cefazolindose
₋ totalcefazolindose
₋ cefazolinclosureconc
₋ cefazolinminconc
Variable OR 95%CI p-value Cefazolinclosureconc(per10%decrease) 1.36 1.02-1.82 0.038
Durationofsurgery(per1hincrease) 2.94 1.13-7.64 0.027
AreaundertheROCcurve(95%CI)=0.789(0.583-0.996)Hosmer-Lemeshowp-value=0.21
Zelenitskyetal.IDWeek2016,NewOrleans,NO.
Cefazolin closure conc & duration of surgery were associated with SSI.
“Thus,themost importantaspect inthe7minganddosingofprophylac7can7bio7csisachievingeffec7velevelsthroughoutthe7methattheincisionisopen.”
“Thus…toprovideserumand7ssueconcsexceedingtheMICsformostprobableorganisms…atthe7meof incision,andforthedura7onoftheprocedure.”
What is “effective” AP?
How can this optimize AP for patients in the clinical setting?
Bratzleretal.AmJHealth-SystPharm2013;70:195-283.
30 40 50 60 70 80 90AGE
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Proportion per B
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Proportion per B
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0.05 0.10 0.15 0.20VDL
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1.0 1.5 2.0 2.5 3.0T12
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Proportion per B
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0.2 0.3 0.4 0.5KE
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Proportion per B
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1 2 3 4 5 6 7 8 9CL
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Cou
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0.02 0.03 0.04 0.05 0.06 0.07 0.08 0.09 0.10CLKG
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0.01
0.02
0.03
0.04
0.05
0.06
0.07
0.08
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0.10
Proportion per B
ar
0
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Cou
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0.05 0.10 0.15 0.20F
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Proportion per B
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0.00
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Proportion per B
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50 60 70 80 90 100 110 120 130CLCR
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0 5 10 15 20 25VD
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Proportion per B
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1.0 1.5 2.0 2.5 3.0T12
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0.02 0.03 0.04 0.05 0.06 0.07 0.08 0.09 0.10CLKG
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Proportion per B
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Proportion per B
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1.0 1.5 2.0 2.5 3.0T12
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Proportion per B
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Proportion per B
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Proportion per B
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CLKG
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Proportion per B
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Proportion per B
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Proportion per B
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Proportion per B
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E.coli32%
MSSA15%
MRSA4%
P.aeruginosa10%
Klebsiellaspp9%
Streptococcusspp9%
S.epidermidis9%
Enterobacterspp8%
Proteusspp4%
30 40 50 60 70 80 90AGE
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Proportion per B
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Proportion per B
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Proportion per B
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Proportion per B
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Proportion per B
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Proportion per B
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Proportion per B
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0.02 0.03 0.04 0.05 0.06 0.07 0.08 0.09 0.10CLKG
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0.01
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0.03
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0.05
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Proportion per B
ar
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Proportion per B
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Proportion per B
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10 20 30 40 50 60 70CP
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Proportion per B
ar
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30 40 50 60 70 80 90AGE
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Proportion per B
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Cou
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0.00
0.02
0.04
0.06
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0.12
0.14
0.16
Proportion per B
ar
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100
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Cou
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50 60 70 80 90 100 110 120 130CLCR
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0.01
0.02
0.03
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0.06
0.07
0.08
0.09
0.10
Proportion per B
ar
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100
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Cou
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0.05 0.10 0.15 0.20VDL
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0.04
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0.06
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0.08
Proportion per B
ar
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100
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Cou
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0 5 10 15 20 25VD
0.00
0.02
0.04
0.06
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0.14
Proportion per B
ar
0
100
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300
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Cou
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1.0 1.5 2.0 2.5 3.0T12
0.00
0.01
0.02
0.03
0.04
0.05
0.06
0.07
0.08
Proportion per B
ar
0
100
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400
Cou
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0.2 0.3 0.4 0.5KE
0.00
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0.03
0.04
0.05
0.06
0.07
0.08
Proportion per B
ar
0
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Cou
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1 2 3 4 5 6 7 8 9CL
0.00
0.01
0.02
0.03
0.04
0.05
0.06
0.07
0.08
0.09
0.10
Proportion per B
ar
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100
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300
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Cou
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0.02 0.03 0.04 0.05 0.06 0.07 0.08 0.09 0.10CLKG
0.00
0.01
0.02
0.03
0.04
0.05
0.06
0.07
0.08
0.09
0.10
Proportion per B
ar
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100
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400
500
Cou
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0.05 0.10 0.15 0.20F
0.00
0.01
0.02
0.03
0.04
0.05
0.06
0.07
0.08
Proportion per B
ar
0
100
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400
Cou
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100 200 300 400FD
0.00
0.01
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Proportion per B
ar
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100
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Cou
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10 20 30 40 50 60 70CP
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0.04
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Proportion per B
ar
0
100
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Cou
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%ofcaseswhereAPcoversprobableSSIpathogens
duringsurgery
MCSn=5,000
Pa0entdemographics–age,wt,Clcr An0microbialPKs–Vd,t½,%free
SSIpathogen,MICdistribu0onsSurgerydura0on
Zelenitskyetal.JAC2016;;71:2902-8.
MonteCarlosimulation(MCS)modelling
Zelenitskyetal.JAC2016;71:2902-8.
Ertapenem1g
Cejriaxone2gGentamicin5mg/kgLevofloxacin500mg
Cefazolin2gCefoxi0n2g
%ofcaseswhereAPcoversallprobableaerobicSSIpathogens
Metronidazole500mgErtapenem1g
Clindamycin900mgCefoxi0n2g
Zelenitskyetal.JAC2016;71:2902-8.
%ofcaseswhereAPcoversallprobableanerobicSSIpathogens
5mg/kg
S.aureusOtherEnterobacteriaceaeE.coliAllSSIaerobes
3mg/kg 1.5mg/kg
Zelenitskyetal.JAC2016;;71:2902-8.
%ofcaseswheregentamicincoversallprobableaerobicSSIpathogens
OtherAPquestions…
“Thus, themost important… is achieving effec7ve levels throughout the7methattheincisionisopen.”(WHOGlobalguidelinesforthepreven0onofSSI2016)
? selec0ngan0microbial
? selec0ngdose
? 0mingpre-opdose
? re-dosingduringsurgery
? con0nuingajersurgery
- Whentousecejriaxoneinsteadofcefazolinincolorectalsurgery?- ShouldazithromycinbeaddedtocefazolininC-sec0ons?(Titaetal,NEJM2016)
- Howtodosecefazolininobesepa0entsie,3gfor>120kg?
Today’s Hospital 2005 – “Why timing is everything with AP and surgery” Medscape ID 2013 – “Surgical AP: Timing doesn’t alter risk”
- Howtoconsiderrenalfunc0oninre-dosing?- Shouldcon0nuousinfusioncefazolinbeusedincardiacsurgery?
Selectreferences(recentprac0ceguidelines,reviewsandresources):
§ Andersonetal.Strategiestopreventsurgicalsiteinfec0onsinacutecarehospitals:2014update.InfectControlHospEpidem2014;34(6):605.
§ Banetal.AmericanCollegeofSurgeonsandSurgicalInfec0onSociety:Surgicalsiteinfec0onguidelines,2016update.JAmCollSurg2017;224(1):59.
§ Bratzleretal.Clinicalprac0ceguidelinesforan0microbialprophylaxisinsurgery.AmJHealth-SystPharm2013;70(3);195.
§ Bronwenetal.Surgicalsiteinfec0ons:anupdate.InfectDisClinNAm2016;30:909.
§ CanadianPa0entSafetyIns0tute:SurgicalSiteInfec0ons(Ge\ngStartedKit)(hQp://www.pa0entsafetyins0tute.ca/en/Topic/Pages/Surgical-Site-Infec0on-(SSI).aspx);(hQp://www.pa0entsafetyins0tute.ca/en/toolsresources/pages/ssi-resources-ge\ng-started-kit.aspx)
§ Najjaretal.Prophylac0can0bio0csandpreven0onofsurgicalsiteinfec0ons.SurgClinNAm2015;95:269.
§ WHOGlobalguidelinesforthepreven0onofsurgicalsiteinfec0on2016(hQp://www.who.int/gpsc/ssi-guidelines/en/)
§ WHOGuidelinesforSafeSurgery2009.(hQp://www.who.int/pa0entsafety/safesurgery/tools_resources/9789241598552/en/)
Thankyou!Questions?
