4/22/17
AppropriateAntibiotic
Prescribing:MakingGoodChoices
forBadBugs
ElizabethO.Hand,Pharm.D.,BCPS
PediatricInfectiousDiseasePharmacist
UniversityHealth System
ClinicalAssistantProfessor
TheUniversityofTexas atAustinCollegeofPharmacy
Disclosure
• Ihavenothing to disclose regardingthe
content ofthis presentation.
Antibioticsaretheonlymedicationin
whichuseinonepatientcanaffect
outcomesinanother.
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NotaLotontheHorizon
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InfectionsMoreDeadlyThanCancer?!
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Objectives
• Describe recent trends inantimicrobial
resistance intheUnited States
• Listthree common bacterial pathogens seen
intheprimary caresetting andavailable
treatment options
• Explain unintentional consequences of
inappropriate antibiotic prescribing
• Identifywaystoimprove appropriate
antibiotic prescribing inclinical practice
ByTheNumbers
• 266.1million antibiotic prescriptions annually
– 30- 50%inappropriate
• >60% ofexpenditures inoutpatient setting
• 80-90%of antibiotic volume in humans
• Mostcommon antibiotics
– Azithromycin and amoxicillin
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U.S.OutpatientAntibioticPrescribing
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N EJM 2013; 368(15)1461-1462.
WhatisAppropriateAntibiotic
Prescribing?
• Usingantibiotics totreat abacterial infection
• Usingthe narrowest spectrum agent(s)
needed tocoverpossible orknown pathogens
• Usingantibiotics fortheshortest timepossible
• Backedbythehighest levelofefficacydata
availabletotreatthe infection inquestion
• ANYTHING ELSEISINAPPROPRIATE
AdaptedfromslidepresentationbyDr.BradSpellberg, SIDPPresentation,Boston,MA2016
WhatAreYOURBiggestChallenges?
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ChallengesintheOutpatientSetting
• Lackofculture-driven therapy
– Viralvs.bacterial
– Fullysusceptiblevs.fullyresistant
• Lackofknowledge ormisconceptions about
resistance
– Majorityofprovidersunabletodescribelocal
trends
• Limited oral antibiotic options
• Perception antibiotics arebenign
AntibioticResistanceThreatsinthe
UnitedStates,CDC2013Report
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1. Drug-resistant
Streptococcus
pneumoniae
2. Extended-spectrum
betalactamase
producing
Enterobacteriaceae
(ESBLs)
a. E.coli
3. MRSA
www.cdc.gov
AntibioticResistance
Porin
Deletion
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Efflux
Altered
Binding
Site
Enzymatic
Breakdown
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MostCommonReasonsforAntibiotics
• Respiratory tractinfections
• Urinary tract infections
• Skin/softtissue infections
PrinciplesofEmpiricAntibiotic
Prescribing
• Presumed activity against>90%ofisolates
• Mostbenign sideeffectprofile
• Supported byclinical evidence
• Affordable forpatient
*Balancing potential risksvs.potential benefit*
MostCommonReasonsforAntibiotics
• Respiratory tractinfections
– Pathogenofconcern:Streptococcuspneumoniae
• Urinary tract infections
– Pathogenofconcern:E.coli
• Skin/softtissue infections
– Pathogenofconcern:Staphylococcusaureus
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Bacterial RespiratoryTractInfections
• Pharyngitis due toStreptococcus pyogenes
(Group Astreptococcus)
• Sometimes bacterial
– Communityacquiredpneumonia(CAP)
– Acutebacterial rhinosinusitis
– Acuteotitismedia(AOM)
• NOTBRONCHITIS
Epidemiology ofCAP
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2%
Jain Set al.N EJM 2015; 373:415-27.
Streptococcuspneumoniae
• 4million infections
– 22,000deathsannually
• Mostcommon
bacterial causeof
– CAP
– Meningitis
– AOM?
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• Immunization WORKS
CDC, Antibiotic Res is tance Threats in the U nited States , 2013. 7
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PneumococcalConjugateVaccine
Impact
• PCV13
– containspolysaccharidesfrompneumococcalserotypes1,
3,4,5,6A,6B,7F,9V,14,18C,19A,19F,and23F
EfficacyRates
• Evaluationof3232visitsforsuspectedpneumoniaor
invasivedisease46% for first episode of
vaccine-type CAP
75% for
vaccine-typecurrently be
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N Engl JMed 2015;372:1114-25.
PneumococcalConjugateVaccine
ImpactinPediatrics
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JPediatric Infect Dis Soc. 2016 Feb22.
ACIPRecommendations forPCV13
• Children
– Fourdoseseriesat2,4,6and12-15months
• Adults >65years
– Single dosefollowedbyPPSV23
• Adults >19withimmunocompromising
conditions
– Single dosefollowedbyPPSV23
www.cdc.gov
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RiskFactorsForPneumonia
•
•
•
•
•
•
•
Smoking
Poor oralhygiene orprosthesis
Malnutrition
Dustexposure inworkplace
Oropharyngeal dysphagia
Contact with children
Nonvaccination againstS.pneumoniae
– PPSV23vs.PCV13
Clin Pulm Med 2016; 23:99–104.
GuidelineRecommendedRegimensfor
CAP
• Previously healthy, noantibiotics inprior 3
months
– Macrolide(à azithromycin)
– Doxycycline
• Significant comorbidities (DM,alcoholism,
malignancy, asplenia, etc),useofantibiotics in
prior 3months
– Respiratoryfluoroquinolone (levo,moxi)
– Betalactam (amoxicillin)plusamacrolide
Clin Infect Dis 2007; 44: S27-72.
Macrolides
• Azithromycin
–
–
–
–
–
Oral
100%bioavailable
Once dailydosing
Fairlybenignsideeffect profile
Activeagainstatypicalpathogens, some
S.pneumoniae
• A wolf insheep’s clothing?
– Driverofpenicillin resistance inS.pneumoniae
– Concern forincreased riskofsudden cardiac death
N EJM 2012; 366:1881-1890.
Clin Infect Dis 2011;53(7):631–639
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FDADrugSafetyCommunication:
Fluoroquinlones
• “Health careprofessionals should not
prescribe systemicfluoroquinolones to
patients who haveother treatment options for
acutebacterial sinusitis, acutebacterial
exacerbation ofchronic bronchitis, and
uncomplicated urinary tract infections
becausethe risksoutweigh thebenefits in
thesepatients.”
FDA Drug Safety Communication,
Safety Announcement,
July 2016.
ReliableAntibioticsforS.pneumoniae
inCAP
• Firstline
– Penicillin,amoxicillin
– Amoxicillin-clavulanic acid
• Second line
– Cefdinir
– Cefuroxime
• Third line
– Respiratoryfluoroquinolones
Sinusitis: Treatment
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IDSA Clinical Practice G uidelines for Acute Bacterial Rhinos inus itis inChildren andAdults . Clin Infect Dis 2011. 10
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AcuteSinusitis:
Treatment
displayed.
AZITHROMYCINNOTRECOMMENDEDFOR
SINUSITISDUETOHIGHLEVELSOF
RESISTANCEINSTREPTOCOCCUS
PNEUMONIAE
IDSA Clinical Practice G uidelines for Acute Bacterial Rhinos inus itis inChildren andAdults . Clin Infect Dis 2011. RespiratoryInfections:TakeHome
Points
• Mostareviral
– Sickcontactsareaclue
• Ifbacterial, mostlyStreptococcus pneumoniae
– Macrolideresistanceisincreasing
– Highdoseamoxicillinisthemostreliableoption
– Fluoroquinolones asalastresort
MostCommonReasonsforAntibiotics
• Respiratory tractinfections
– Pathogenofconcern:Streptococcuspneumoniae
• Urinary tract infections
– Pathogenofconcern:E.coli
• Skin/softtissue infections
– Pathogenofconcern:Staphylococcusaureus
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E.coli
• Majorcauseofuncomplicated urinary tract
infections andpyelonephritis
• Highlysusceptible tomulti-drug resistant
Godzilla bug
• Antibiotic therapyshould useacombination
oftheantibiogram andpastantibiotic
exposure
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HaveYouRecentlyTraveledtoIndia?
displayed.
• E.coli
– 83%resistancetoceftriaxone
– 84%resistancetofluoroquinolones
– 11%resistancetocarbapenems
CCEDPResistance Map,2014.
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E.Coli inSanAntonio
Amoxicillin
Ampicillin-sulbactam
Cefazolin
Cefpodoxime
SMX/TMP
Ciprofloxacin
Nitrofurantoin
%susceptible
44
54
83
84
65
75
93
“Susceptible”basedonabilitytoclearasystemicinfection
OralEmpiricOptions forE.coli
• Nitrofurantoin
– Onlyuncomplicated cystitis
• Sulfamethoxazole/tri methopri m
• Ciprofloxacin, levofloxacin
• Oral third generation cephalosporins
– Cefpodoxime, cefdinir
– $$$
• Fosfomycin
– 3gramsingle dose (aka“theFosfo bomb”)
– $$$
Which AgentisBest?
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• Possiblyalgorithm
• FirstuncomplicatedUTI?
• Nitrofurantoin
• FirstcomplicatedUTI
• Sendforculture
• Ciprofloxacin
• RepeatUTIs
• Sendforculture
JAMA 2014;312(16):1677- 168 4.
Early clinicaland
bacterial cure
>~90%formost
regimens
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BewareAsymptomaticBactiuria
• Diagnosis ofUTI
– Symptoms (akadysuria) +positiveculture
– Symptoms +positive urinalysis
• Discharge + dysuria?
– Don’t forgetsexuallytransmitted diseases
• Only treat asymptomatic bactiuria inSPECIFIC
populations
– Pregnantwomen, thoseunderlying GI/GU surgery,
immunosuppressed patients (+/-)
UrinaryTractInfections:TakeHome
Points
• E.coli is aproblem
– Resistance increasing withno signsof slowing down
– MDR pathogens becoming more common in the
community
• Reserve broader spectrum agents forsecond UTI
or more complicated cases
– Nitrofurantoin preferred firstline
• Send for culture, even though results are delayed
MostCommonReasonsforAntibiotics
• Respiratory tractinfections
– Pathogenofconcern:Streptococcuspneumoniae
• Urinary tract infections
– Pathogenofconcern:E.coli
• Skin/softtissue infections
– Pathogenofconcern:Staphylococcusaureus
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Staphylococcusaureus
• Gram positive cocci
• Three “flavors”
– Penicillin susceptible
– Methicillin susceptible (MSSA)
– Methicillin resistant(MRSA)
• Varying mechanisms ofresistance
– Penicillin susceptible à penicillin resistant
• Beta lactamaseproduction
– Methicillin susceptible à methicillin resistant
• Alterationinbindingsite
MRSAakaTHEKING
• Colonizes ~30%ofUSpopulations
• >80,000 invasiveinfections annually
– Bacteremia, endocarditis,pneumonia,boneand
jointinfections
– >11,000deaths
• WhyisMRSAso
muchworse?
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www.cdc.gov
Clin Microbiol Rev 2015; 28(3): 603-61.
HowWe GotHere
1960
FirstMRSA
isolate
identified
1981
MRSA
outbreak
amongstIVDU
in Detroit
1998
25fold
increasein
rateof
hospitalizatio
ns dueto
MRSAin
patientswith
norisk factors
2003-2008
MRSA
infectionsin
USacademic
centers
double
IncreaseinED
visits dueto
MRSASSTIs
from1.2to
3.4million
U nivers ity of Chicago MRSA Res earch Center
http:/ / mrs a-res earch-cent er.bs d. uchicag o.ed u/ tim eline. ht ml
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TheEmergenceofMRSA
70
60
Prevalence
50
40
All pts
ICU
30
UHInpts
UHOutpts
20
10
0
1998
2000
Ann Clin Microbiol
Antimicrob 2006
U HS Antibiograms
1998-2009
2002
2004
2006
2008
MRSAinRecentYears
• Significant reductions inMRSAbacteremia
since2005
– 30%reductioninhospital-associatedMRSA
infections
• Possible slight reduction inMRSAskin/soft
tissue infections inthe lastdecade
• Morbidity andmortality remain high
WhereAreWeNow?
• Community onsetMRSA
– ~40-45%ofallS.aureus infections
• Common causeofskin/softtissue infections
• Rare causeofcommunity-acquired
pneumonia
– <1%
• Canaffectanyone,certain riskfactors doexist
– IVDU,hemodialysis,FQuse?
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MRSAbyAge
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Guidelines forSSTIManagement
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IDSAGuidelinesforManagementofSSTIs,2014.
MRSAManagement
• Vancomycin
– Preferred agentforsevere,invasiveinfections
requiring intravenoustherapy
• Oral antibiotic options
–
–
–
–
–
Sulfamethoxazole/trimethoprim
Doxycyline
Minocycline
Clindamycin
Linezolid
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OralOptions forMRSA
• Highly active invitro (>95%)
– Sulfamethoxazole/trimethoprim
• Sulfaallergy,rash,hyperkalemia
– Linezolid
• Druginteractions(SSRIs),peripheralandopticneuropathy,
bonemarrowsuppression,wallettoxicity
– Doxycyline, minocycline
• GIupset,bindingofdivalentcations
• Modest activity (60-70%)
– Clindamycin
• C.difficile associateddiarrhea
NewKids ontheBlock
• Dalbavancin, oritavancin
– Intravenous agentswithactivityagainstMRSA
– Approved in2014for acute bacterialskin/skin
structure infections
– Halflivesrangefrom 10-14 days
– 1to2dose regimens
• $$$$$
• Jury still outonclinical utility
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Nothing
Kills
likea
BetaLactam
IDSAGuidelinesforManagementofSSTIs,2014.
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AvoidableAntibioticExposureinSSTIs
• Retrospective cohort studyinColorado
• 364cases(pediatric andadult)
– 155cellulitis,168abscess
• 139casesofdrained abscesses
– Antibioticsgivenin80%ofcases
– Average 7dayduration
• Overall46%ofallantibiotic usewasdeemed
AVOIDABLE
Am J Med 2013; 126(12)1099-1106.
SkinSoftTissueInfections:TakeHome
Points
• Purulence? à think Staphylococcusaureus
–IF anantibiotic isneeded, cover forMRSA
• SMX/TMP,doxycycline,linezolid
• Non-purulent
– Cephalexin
– Clindamycin
• Five daysisenough
TipsonPickingtheRightDrug
DRUG
•
•
•
•
BUG
Interactionevaluatedinthemicrobiologylab
Effectofdrugonbugatasetconcentration
Staticinteraction
ONEPIECEOFTHEPUZZLE
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BUG
DRUG
DOUG
WrappingUp
• Antibiotics are a shared resource
• Mostantibiotic prescribing occurring in the
outpatient setting
• Limited development innew antibiotics
• Knowing your resistant pathogens and treatment
optionsis key
CDC12StepstoReducingAntibiotic
Resistance
• 1.Vaccinate
• 2.Get thecatheters out
• 3.Target the pathogen
• 4.Accesstheexperts
• 5.Practice antimicrobialcontrol
• 6.Uselocaldata
• 7.Treat infection,notcontamination
• 8.Treat infection,notcolonization
• 9.Knowwhentosay“no”tovanco
• 10.Stoptreatment when infectioniscuredorunlikely
• 11.Isolatethepathogen
• 12.Containthecontagion
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VS.
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Thankyou!
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