HD1InfectiousDisease

IntroductiontoInfectiousDiseaseI&II
I) ApproachestoClinicalSituations
A) Approachtopatient
1) Symptomsorsigns
2) Constellationoffindings
3) Considerpatienthostdefenses
4) Isthisaninfectiousdiseaseorsomethingelse?
5) Inflammationanddistanteffects
B) Approachtodiagnosis
1) Patienthistoryis90%ofthediagnosis
2) Physicalexam
3) Tests
(a) Gramstainandcultureworktogethertoidentifypathogenicorganisms
4) Empiricaltreatmentifappropriate/necessary
5) Prevention
C) Approachtoclinicalmicrobiology
1) Draw2setsofbloodcultures
(a) Organismsisolatedonlyfrombrothareoftencontaminants,whichmakeup1020%ofall
positivecultures
2) Organismshavedifferentcapacitiesforinfection(colonization)anddisease
(a) Certainorganismscancausediseaseinanyhost
(i) Staphylococcusaureus
o Treatwithlactamsorvancomycin
(ii) GroupAstreptococci
(iii)
Streptococcuspneumoniae
D) Approachtotreatment
1) Infectiousdiseasestypicallyprogressslowly,givingthephysiciantimetomakethecorrectdiagnosis
II) BayesTheorem
A) Probabilitymodelthatcanbeusedtopredictdiseaseincidence
B) Example
1) Givenconditions
(a) 1%ofwomenatage40whoparticipateinroutinescreeninghavebreastcancer
(b) 80%ofwomenwithbreastcancerwillgetpositivemammographies
(c) 9.6%ofwomenwithoutbreastcancerwillalsogetpositivemammographies
2) Question
(a) Ifawomaninthisagegrouphasapositivemammographyataroutinescreening,whatisthe
probabilitythatsheactuallyhasbreastcancer?
3) Solution
(a) Assumingapopulationof10,000suchwomeninthisagegroupwhoallparticipateinroutine
screening,100ofthemwillhavebreastcancer(the1%)
(i) 80%ofthose100womenwillhavepositivemammographies
(b) Fromthesame10,000women,theremaining9,900willnothavebreastcancer
(i) 950ofthemwillhavepositivemammographies(the9.6%)
(c) Thus,thetotalnumberofpositivemammographiesis1,030
(i) Ofthesewomen,however,only80ofthemactuallyhavebreastcancer
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80 cases
=7.8 liklihood
1,030 positive screens
III) StagesofDevelopmentandRelatedInfections
A) Infants
1) Lackantibodiesoftheirownuntil~5monthsofage,makingthemparticularlysusceptible
2) Streptococcuspneumoniae
3) Neisseriameningitidis
4) Haemophilusinfluenzae
5) Shigellaspp.
6) Escherichiacoli
7) Rotavirus
B) Adolescents
1) Hostdefensesaretypicallyfine
2) Behavioralrisksforinfectiousdisease
C) Elderly
1) Innateandadaptivedefensesdecline
IV) MiscellaneousTopics
A) Colonizationresistance
1) Nativefloraprotectagainstcolonizationbyapathogenicorganism
2) Majorimpairmentcomesfrommicrobialuse
(a) E.g.,Clostridiumdificile
B) Feverandneutropenia
1) Thereisastrongqualitativerelationshipbetweeninfectionandneutropeniaonceathresholdhas
beensurpassed(<1,000granulocytes/L)
C) Complementdeficiency
1) Increasesriskofinfectionbyencapsulatedorganisms
(a) Neisseriameningitidis
(b) Streptococcuspneumoniae
(c) Haemophilusinfluenzae
(d) Treatthesewithceftriaxone
D) Aspleniaorsplenicdysfunction
1) Lossofsplenicfunctionincreasespredispositiontoseveralpathogenicorganisms
2) Riskofinfectionisgreatestinthefirstyearanddiminishesovertime
E) Conditionsthatimpairhostdefenses
1) Malnutrition
2) Diabetes
3) Antibodydeficiency
F) Rapidempiricaltreatmentisindicatedinsomescenarios
1) Bacterialmeningitis
2) Acuteendocarditis
3) Severesepsis/shock
4) Necrotizinginfection
5) Toxicshocksyndrome
(ii)

ApproachtoAntimicrobialChemotherapy
I) TypesofAntimicrobialTherapy
A) Prophylaxis
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1) E.g.,endocarditisprophylaxispriortosurgery
B) Preemptivetherapy
1) E.g.,treatingsubclinicalCMVinfectionsinBMT/organtransplantpatients
C) Empirictherapy
1) Definedastheuseofantibioticsinapatientwithasuspectedinfectionbeforethemicrobiologyof
theinfectionisknown
2) Microbiologytestturnaroundcanbeslowerthandesired
3) Scenariosinwhichempirictherapyisused
(a) Immunocompromisedpatients(neutropenia,asplenia,etc.)
(b) Suspectedbacterialmeningitis
(c) Septicshock
(d) Necrotizinginfections
4) Choosingempirictherapy
(a) Oftenbroadspectrum,butbasedonbestpredictionofmicroorgansimsinvolvedandtheir
susceptibility
(b) Antibiogram
(i) Generatedbyhospitalseverysixmonths(orayearorso)
(ii) Yaxisrepresentsorganismstestedonsite,Xaxisrepresentssusceptibility
(iii)
Givesthepercentageofbacterialcasesthatweresusceptibletospecificantibiotics
D) Pathogendirectedtherapy
1) Theorganismisknown,butantibioticsusceptibilityisnot
2) Mustconsiderlikelyresistanceprofilesinthatpatient,region,and/orICU
3) Canconsultangiogramifavailable
E) Susceptibilityguidedtherapy
1) Bestcasescenario,wherebothorganismandsusceptibilityareknown
2) Canstreamlinetherapybasedonmosteffective,leasttoxic,cheapest,etc.
3) Susceptibilitiesareoftenbasedontheminimuminhibitorconcentration(MIC)
(a) Providesthelowestconcentrationofantibioticthatpreventsgrowth
(b) Bacteriallocation(e.g.CSFinmeningitis)maydeterminewhetherornottheMICisinterpreted
asaresistant/susceptibleinfection
II) AlteringTherapy
A) SteppingdowntherapyfromIVtoPO(bymouth)
1) Patientisclearlyimproving
2) Gutishealthy
3) Donotstepdowntherapyincasesofmeningitis,endocarditis,andStaphylococcusaureus
bacteremia
B) Broadtonarrowspectrum
1) Basedoncultureresults
2) Basedonclinicalresponse
C) Discontinuingtherapy
1) Clinicalcourseisinconsistentwithinfection
III) HarmsofAntimicrobialTherapy
A) Relatedtoantimicrobialeffect
1) C.difficilecolitis
2) Othersuperinfections
3) Resistance
4) Interferencewithdiagnosticworkup
B) Adversedrugeffects
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1) Allergy
2) Toxicity
C) Drugdruginteractions
1) ImportantwithdrugsthataffectCYP450(e.g.warfarin)
D) IVaccesscomplications
1) Clots
2) Infection(local,bloodstream,etc.)
E) Costs
1) Drug
2) Administration
3) Labs