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DurationofTherapy

MattGreeneVanderbiltUniversityMedicalCenter,InfectiousDiseases

15September2017

Outline1. Principles– “lowhangingfruit”– Goldilockszone

2. Guideposts– resources• Nelsonetal• IDSAGuidelines

– datafreezone(DFZ)

Outline3. Infections– SSTI– pneumonia• CAP• HAP/VAP

– urinaryinfection• cystitis• pyelonephritis• CAUTI

– abdominalabscess– CLABSI

• BackgroundStudies• IDSA/Sanford

Principles“Zerodaysoftherapyisanice,shortduration.”

Heckeretal• 650nonICUpatients• 2weekprospectiveobservational• approx 30%ofdaysoftherapyunnecessary

TrivediSHEA2017Heckeretal.ArchInternMed2003

PrinciplesGoldilocksZone• Q:“Howmuchantibiotics?”• A:“Justenough.”

Pros• ↓resistance• ↓adversereactions• ↓lengthofstay• ↓cost

Cons• blowback• DFZ

HotontheCase!21yo malewrestler- 3cmboilonrightthigh- I&D=MRSA- you’regoingwithTMP/SMX

A. 3daysB. 5daysC. 7daysD. 10daysE. 14days

Skin&SoftTissueInfection

Skin&SoftTissueInfection• Jenkinsetal2010

• Holmesetal2016• pediatricrandomized,non-inferiority(n=249)• excluded• nodrainage(ie,onlyabscesses)• immunecompromised• inpatient

• TMP/SMX3dvsTMP/SMX10d

JenkinsCID2010HolmesJPediatr 2016

Skin&SoftTissueInfection• Talanetal2016• randomized,double-blindsuperiority(n=1265)• excluded• <12yearsofage• <2cmfluctuantlesion(ie,onlyabscesses)for<1week• inpatient

• TMP/SMX7dvsplacebo

TalanNEJM2016

Skin&SoftTissueInfection• Duam etal2017• randomized,double-blind,superiority(n=786)• 281(36%)children

• excluded• >5cmabscess• inpatient

• clindamycin10dvsTMP/SMX10dvsplacebo• endpoint=clinicalcure7-10dlater

Duam NEJM2017

Skin&SoftTissueInfectionIDSA

Sanford“Until3daysafteracuteinflammationdisappears”

StevensetalCID2014SanfordGuideAntimicrobialTherapy

HotontheCase!62yo retiredfemalelibrarian- 9daysofpurulentcough+fever- sputum=Strep.pneumoniae- you’regoingwithceftriaxone


CommunityAcquiredPneumonia

CommunityAcquiredPneumoniaBackgroundStudies• Dunbaretal2003• randomized,double-blind,active-treatment

controllednon-inferiority(n=528)• excluded• knownresistanceorhighriskforPseudomonas• aspirationorempyema• neutropeniaorHIV+• meningitis

• LVQ750mgdaily5dvsLVQ500mgdaily10d

DunbarCID2003

CommunityAcquiredPneumonia• Lietal2007(meta-analysis)

• metaanalysisof15RCTs(n=2796)• excluded• children• aspiration• pneumocystis

• shortcourse(<7d)vslongcourse(>7d)

LiAmJMed2007

CommunityAcquiredPneumoniaIDSA=DFZ• “Thecommitteechosenottoaddress…”• solidorgan/bonemarrow/stemcellrecipients• receivingchemotherapy• long-term(>30days)corticosteroids• congenitalnoracquiredimmunodeficiencies• CD4<350

• <18yearsofage

MandellCID2007

CommunityAcquiredPneumoniaIDSA

Sanford

MandellCID2007

CommunityAcquiredPneumoniaIDSA

Sanford“5days(minimum)anduntilafebrilefor2-3days”

MandellCID2007

Hospital/VentilatorPneumonia• Chastre etal2003• prospective,double-blinduntilday8(n=197)• excluded• children• nomicrobiologicdiagnosis(ie,required+BAL)• <48hrsventilation+<5daysonsetofpneumonia• neutropenia/>1monthsteroids/AIDS• extrapulmonary infection

• 8dvs15d

Chastre JAMA2003

Hospital/VentilatorPneumonia• Hedricketal2007• retrospectivesubgroupNFGNB(n=154)• 3-8dtherapy(n=27)vs>9(n=127)

• nomortalitynorrecurrencedifference

• Dimopoulos etal2013• meta-analysisof4RCTs(n=883)• 7-8dvs10-15d

HedrickSurg Infect2007Dimopoulos Chest2013

Hospital/VentilatorPneumoniaIDSA

Sanford“Notwelldefined”• 8dfor“relativelysusceptiblepathogens”• 14dforMRSA,PSA,Acineto,Steno,etc.

Kalil CID2016

HotontheCase!30yo femalemedicineresident- 2daysofdysuria- UA=>600WBCsgrowingE.coli- you’regoingwithnitrofurantoin


CystitisBackgroundStudies• Trienekens etal1989• randomized,double-blind,placebo-controlled

(n=327)• excluded• <12yearsofage• GUabnormality/pregnant• signs/symptomspyelonephritis• immunesuppressed(includingdiabetics)

• 3dv7dTMP/SMX• norecurrenceat1,2and6weeks

Trienekens BMJ1989

Cystitis• Iravani etal1999• randomized,double-blind(n=521)• 3dcipro vs7dTMP/SMXv7dnitrofurantoin• norecurrenceat4-6weeks

• cipro =91%,TMP/SMX=79%,nitro=82%

• Guptaetal2007• randomized,open-label(n=338)• 3dTMP/SMXvs5dnitrofurantoin• clinicalcureat30days

Iravani JAntimicrob Chemother 1999GuptaArchInternMed2007

CystitisIDSA+Sanford

GuptaCID2011

PyelonephritisBackgroundStudies• Talenetal2000• randomized,double-blind,placebo-controlled

(n=255)• CVAtenderness+fever+pyuria• excluded• <18yearsofage• sepsis• GUabnormality/pregnant• immunecompromised(includingdiabetes)• renaldysfunction

• 7dciprofloxacin+7dplacebovs14dTMP/SMXTalenJAMA2000

Pyelonephritis• Klausner etal2007• double-blind,non-inferiority(n=311)• excluded• obstruction• eGFR <50• knownresistance

• 5dLVQ750mgPOdailyvs10dcipro 500mgPOBID

Klausner Curr MedResOpin 2007

PyelonephritisIDSA• 5dLVQ750mgPOdaily• 7dciprofloxacin500mgPOBID• 14dTMP/SMXPOBID• “oralβ lactamsarelesseffective”• “insufficientdata”=10-14d

Sanford• 5dLVQor 7dciprofloxacinor 14dother

GuptaCID2011

CAUTI“The mostcommonhealthcare-associatedinfectionworldwide.”

IDSA• 7dif“promptresolution”• 3difwoman≤65yearsoldwithoutUUTS• 5dLVQifnot“severelyill”

• 10-14dif“delayedresponse”

Sandford• seeHootonetalCID2010

HootonCID2010

AbdominalAbscessIDSA• 4-7dafter“adequatesourcecontrol”• 24hforperforationcontrolled<24hrs• ≤24hrsforpenetratinginjuryrepaired<12hrs• onlypre-operativeforsimpleappendicitis• i.e.,noperforationnorabscess

Solomkin CID2010

AbdominalAbscess• Sawyeretal2015• randomized,open-label(n=518)• compositeendpoint=SSI,recurrenceordeath• monitoringfever+leukocytosis+ileus

• excluded• <16yearsofage• lackofsourcecontrol

• determinedbyPIandlocalinvestigator

• 2dafterresolutionvs“fixed”4±1d

SawyerNEJM2015

HotontheCase!71yo malenursinghomeresident- 3daysoffeverandchills- bloodcultures+PICC=MRSE- you’regoingwithvancomycin


CLABSIIDSA

Mermel CID2009

Questions?

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