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Mdm Ang BeeChanisa55-year-oldChineseFemalewhoisADLindependentandcommunityambulant.Sheisanonsmokerandnonalcoholic.Herpremorbids includeT2aN1M0StageIIBLeftBreastCancerER-,PR+,Her2-ve,status-postmastectomyandaxillaryclearanceandiscurrentlyonadjuvantchemotherapy.SheiscurrentlyundergoingDoxorubicinandCyclophosphamideQ3weeklyfor4cyclesviaaCentralCatheterLine.Herotherpremorbids includeprevioushaemorrhoids andhypertensiononamlodipine5mg.
Shepresentswitha2dayshistoryoffeverofmax37.8aswellasbreathlessnessonwalking.Thereisnochestpainorpalpitations,nodiaphoresis.Shecomplainsofamildcoughandsorethroat.Onexamination,hervitalsareBP110/67,HR60,RR22,SpO295%onRA.Temp38.0.Sheisalertandspeakingfullsentences,conjunctivaearepale.Sheislookingalittlelethargicaswell.HS1S2noaudiblemurmurs.Lbilaterallyairentryintactnoobviouscrepitations.Asoftnontender.
YouaretheEmergencyMO,whataresomeofthekeyexaminations/investigationsyouwouldliketodo?(Choose5outof11)ABGStat FullBloodCountwithdifferentialcounts RenalPanelLiverPanel PeripheralBloodCultureX1 PeripheralBloodculture(peripheral+line)DRE CXR CTThorax UrineDipstick
Mdm Ang BeeChanisa55-year-oldChineseFemalewhoisADLindependentandcommunityambulant.Sheisanonsmokerandnonalcoholic.Herpremorbids includeT2aN1M0StageIIBLeftBreastCancerER-,PR+,Her2-ve,status-postmastectomyandaxillaryclearanceandiscurrentlyonadjuvantchemotherapy.SheiscurrentlyundergoingDoxorubicinandCyclophosphamideQ3weeklyfor4cyclesviaaCentralCatheterLine.Herotherpremorbids includeprevioushaemorrhoids andhypertensiononamlodipine5mg.
Shepresentswitha2dayshistoryoffeverofmax37.8aswellasbreathlessnessonwalking.Thereisnochestpainorpalpitations,nodiaphoresis.Shecomplainsofamildcoughandsorethroat.Onexamination,hervitalsareBP110/67,HR60,RR22,SpO295%onRA.Temp38.0.Sheisalertandspeakingfullsentences,conjunctivaearepale.Sheislookingalittlelethargicaswell.HS1S2noaudiblemurmurs.Lbilaterallyairentryintactnoobviouscrepitations.Asoftnontender.
YouaretheEmergencyMO,whataresomeofthekeyexaminations/investigationsyouwouldliketodo?(Choose5outof11)ABGStat FullBloodCountwithdifferentialcounts RenalPanelLiverPanel PeripheralBloodCultureX1 PeripheralBloodculture(peripheral+line)DRE CXR CTThorax UrineDipstick
APPROACH TO COUGHAcute < 3 weeks
Subacute3-8 weeks
Chronic >8 weeks
Respi « URTI« Asthma exac« COPD exac« Acute bronchitis « PE« Pneumonia
« Post infective « Other
acute/chronic causes
« PND *commonest cough (allergic rhinitis)
« Chronic bronchitis/ COPD« Cough variant asthma« Bronchiectasis « Tb « Malignancy « Pulmonary fibrosis « Recurrent aspiration « Sarcoidosis
Cardio « APO« Decompensation
« Heart failure
Others « Drugs « Croup « ALTB« Foreign body
« Drugs – Ace i« GERD « Chemical/ Occupational« Smoker’s cough« Psychogenic
To rule out (Red flags)
« PE« APO« Pneumonia
« Malignancy « TB
Aetiology
APPROACH TO FEVER AetiologyDisorder Common Uncommon RareMalignancy10-30%
Lymphoma Hypernephromas
Preleukaemias/ myelodysplastic syndromesHepatomasMyeloproliferative disorderMetastases to liver
Atrial myxomaMultiple myelomaCNS tumoursRenal cell caPancreatic caColon caSarcomas
Infections20-40%
including inadequately treated infx
TuberculosisIntra-abd abscessSubacute bacterial endocarditisTyphoidMalaria Prostatitis
EBVCMV Splenic abscessAbscessesOsteomyelitisCat scratch feverProstatitis
Chronic sinusitisVertebral osteomyelitisBrucellosis HistoplasmosisLyme diseaseHIV
Rheumatologic15-20%
Still’s diseasePolymyalgia rheumatica
RA SLEKikuchi’s diseaseBehcet’s diseaseTemporal arteritisRheumatoid feverIBD
Misc10-25%
Drug feverHabitual hyperthermia
Pulmonary embolism HaematomaFamilial fevers Hyperthyroidism
PhaeochromocytomaAdrenal insufficiency Liver cirrhosisDeep vein thrombosisSarcoidosis Factitious feverCardiac myxoma
FEVEREstablish patient group
■ Community acquired
■ Nosocomial
■ Immunocompromised
■ Returning traveler
■ Drug fever
■ Post-transfusion
■ Post-op
■ Fever in patient with foreign body (indwelling catheters, vp shunt, metallic valve)
FEVERFeverhistoryHeight,duration,frequency,associatedchillingorsweatsFeverpattern/descriptionUseofantipyretics– doesithelp?
Localizingsymptomsofinfection/systemicreviewSystemsreview:infective/connectivetissue/malignancy/drugs/miscLocalizingsymptomsofinfxJointpainLymphadenopathyCalfswelling,pain,redness– dvtConstitutional:nightsweats,fever,weightlossTravelhistory/ContacthistoryTravel:destination,durationofstay,dateofreturn,(mayworkoutincubationperiod)prophylaxis,pre-travelvaccinations,hygienelevel,freshwater,food,contactwithanimalsunprotectedsex
Drug(drugsmaycausefever)Antibioticuse– isoniazid,penicillin,erythromicin,Chemotherapy,Others:allopurinol,heparin,procainamide,phenytoin,
PmhxRecenthospitalizationForeignbodyinsitu/linesMalignancy- lymphomaChronicillnessesPreviousinfections/recurrentinfx:MSSA/MRSA(ifnotadequatelyRx,IEnotR/O),Undrainedabscesses,Indwellingprosthesis(includingAVGs),RecurrentUTIandkidneystonesVaccinationImmunosuppression:oldage,DM,malignancy(lymphoma,leukemia,myeloma),chronicsteroids,immunosuppressants andorganrecipients,AIDS,asplenia&complementdefectsSurgeries:Turp,Dentalextraction
Socialhistory:Occupation,Hobbies+interest,SexualHx
Familyhx:Familialfevers
Previousmanagement:Includingabx,antipyretics
Mdm Ang BeeChanisa55-year-oldChineseFemalewhoisADLindependentandcommunityambulant.Sheisanonsmokerandnonalcoholic.Herpremorbids includeT2aN1M0StageIIBLeftBreastCancerER-,PR+,Her2-ve,status-postmastectomyandaxillaryclearanceandiscurrentlyonadjuvantchemotherapy.SheiscurrentlyundergoingDoxorubicinandCyclophosphamideQ3weeklyfor4cyclesviaaCentralCatheterLine.Herotherpremorbids includeprevioushaemorrhoids andhypertensiononamlodipine5mg.
Shepresentswitha2dayshistoryoffeverofmax37.8aswellasbreathlessnessonwalking.Thereisnochestpainorpalpitations,nodiaphoresis.Shecomplainsofamildcoughandsorethroat.Onexamination,hervitalsareBP110/67,HR60,RR22,SpO295%onRA.Temp38.0.Sheisalertandspeakingfullsentences,conjunctivaearepale.Sheislookingalittlelethargicaswell.HS1S2noaudiblemurmurs.Lbilaterallyairentryintactnoobviouscrepitations.Asoftnontender.
WHO– 55,ECOGgood,Fit.Malignancys/pcurativeoperation.
WHAT– Fever.Coughandsorethroat
WHY– ?Infection
WHEN– 2days
HOW– SickorNotSick?!
Patientwassubsequentlybroughtuptotheward.YouarenowtheclerkingHOandyouareseeingthispatientforthefirsttime.Sheisabletogiveyouafullhistory.Shecomplainsofhavingacoughandsorethroatforabout3daysduration.NotedtohavefeverathomeofTMax 38.0.Hasbeendrinkingwaterbutduetothepaininherthroat,ithasbeendifficult.AbletoPUandBOwithnodifficulties,occasionallybloodstainedduetoherhaemorrhoids.Shehasnonauseanovomitting Herlastchemotherapywas1weekago.Astheon-callHO,youaresenttoclerkthepatient,kindlyanswerthebelowquestionsinshortanswers.
ShetellsyouthatshehastheCVClineinherforabout2monthsnowforherbloodtakingandchemotherapySheexplainedthatthisisher3rdcycleofchemotherapyHR nowis95,RR22,T38.0BP110/50LungauscultationrevealsintermittentcrepitationsHS1S2nomurmurBasiclaboratorystudiesperformedbytheA&Ereveal:
Hb 7.2(frompreviousbaselineof10.2)TW1.45AbsoluteNeutrophilCount0.73Plt 55
Anelectrocardiogramshowssinustachycardia.TheCXRisshownbelow.
Q3.Whatisthediagnosisforthepatient?(Answerbrieflyin1/2words)
Na137K3.8Cl104HCO322Cr50,CrtCL >100Troponinsnormal
■ A irway■ B ones■ C ardiac■ D iaphragm■ E ffusion■ F ields (lung)■ G astric bubble■ H ilum
/mediastinum
ShetellsyouthatshehastheCVClineinherforabout2monthsnowforherbloodtakingandchemotherapySheexplainedthatthisisher3rdcycleofchemotherapyHRnowis95,RR22,T38.0BP110/50LungauscultationrevealsintermittentcrepitationsHS1S2nomurmurBasiclaboratorystudiesperformedbytheA&Ereveal:
Hb 7.2(frompreviousbaselineof10.2)TW1.45AbsoluteNeutrophilCount0.73Plt 55
Anelectrocardiogramshowssinustachycardia.TheCXRisshownbelow.
Q3.Whatisthediagnosisforthepatient?
Na137K3.8Cl104HCO322Cr50,CrtCL >100Troponinsnormal
FEBRILE NEUTROPENIA
Fever T>38.3 once or T>38 for more than 1h
ANC <500 (or <1000 predicted to drop<500)
Usually happens 10-14 DAYS AFTER CHEMO (dep on regimen)
MEDICAL EMERGENCY
Potentially fatal if not treated appropriately
Febrile neutropenia
CommonsideeffectofchemotherapyLowneutrophilsà immunocompromisedANC<1.0x109/Là neutropeniaANC<0.5x109/Là severeneutropenia
Don’tbecaughtoutbyTotalWBCà calculatetheANC
WHAT BLOODS SHOULD I DO?IDSA Guidelines: Neutropenic FeverFBC+UECR+LFT
Atleast2setsofbloodculturesarerecommended,withasetcollectedsimultaneouslyfromeachlumenofanexistingcentralvenouscatheter(CVC),ifpresent,andfromaperipheralveinsite;2bloodculturesetsfromseparatevenipuncturesshouldbesentifnocentralcatheterispresent(A-III).
Bloodculturevolumesshouldbelimitedto,1%oftotalbloodvolume(usually>70mL/kg)inpatientsweighing,40kg(C-III).
Culturespecimensfromothersitesofsuspectedinfectionshouldbeobtainedasclinicallyindicated(A-III).
Achestradiographisindicatedforpatientswithrespiratorysignsorsymptoms(A-III).
Q4.Astheon-callHO,whichofthefollowingtherapies
wouldyouinitiate?(Choose3of10)FluidchallengewithNacl 0.9%1.5L Fluidchallengewith5%Albumin
NebSalbutamol FungalCulture
StartIVCeftriaxonewithPODoxycycline StartIVCefepime
StartIVAztreonam Transfuse500mlFFP
Transfuse1unitofpackedredbloodcells StartSubcutaneousGCSF
Q4.Astheon-callHO,whichofthefollowingtherapies
wouldyouinitiate?(Choose3of10)FluidchallengewithNacl 0.9% Fluidchallengewith5%Albumin
NebSalbutamol FungalCulture
StartIVCeftriaxonewithPODoxycycline StartIVCefepime
StartIVAztreonam Transfuse500mlFFP
Transfuse1unitofpackedredbloodcells StartSubcutaneousGCSF
WHAT ABX SHOULD I GIVE?IDSA Guidelines: Neutropenic FeverHigh-riskpatientsrequirehospitalizationforIVempiricalantibiotictherapy;monotherapywith■ anantipseudomonalb-lactamagent,suchascefepime,acarbapenem
(meropenem orimipenem-cilastatin),orpiperacillin-tazobactam,isrecommended(A-I).
■ Otherantimicrobials(aminoglycosides,fluoroquinolones,and/orvancomycin)maybeaddedtotheinitialregimenformanagementofcomplications(eg,hypotensionandpneumonia)orifantimicrobialresistanceissuspectedorproven(B-III).
ROLE OF GCSFFilgrastim is a growth factor that stimulates the production, maturation, and activation of neutrophils (a type of white blood cell).
Filgrastim also stimulates the release of neutrophils from the bone marrow.
In patients receiving chemotherapy, filgrastimcan accelerate the recovery of neutrophils, reducing the neutropenic phase (the time in which people are susceptible to infections).
WHAT ABOUT GCSF?IDSA Guidelines: Neutropenic FeverProphylacticuseofmyeloidCSFs(alsoreferredtoashematopoieticgrowthfactors)shouldbeconsideredforpatientsinwhomtheanticipatedriskoffeverandneutropeniais>20%(A-II).
CSFsarenotgenerallyrecommendedfortreatmentofestablishedfeverandneutropenia(B-II).
Bythenextmorning,theprimaryteamhasarrivedandisseeingthepatient.Itturnsoutthatyouhavebeenallocatedtooncologyafteryourcallandnowyouarethepatient'smaindoctor.Whenyouassessthepatientagainaftergivinghertheantibiotics,hersaturationscontinuedtoworsenSheisnotspeakinginshortphrases.Thereisnoaudiblewheezehowevertherearebilateralcrepitations.Despitegivingherantibiotics,shecontinuetofeelbreathless.Theimpressionfromtheprimaryteamnowis:NeutropenicSepsis
Q5.AllofthefollowinginvestigationsarereasonabletoorderedEXCEPT(Choose1):
Bronchoscopy ColonoscopyCTThorax CoagulationProfileTransthoracicEchocardiogram
Bythenextmorning,theprimaryteamhasarrivedandisseeingthepatient.Itturnsoutthatyouhavebeenallocatedtooncologyafteryourcallandnowyouarethepatient'smaindoctor.Whenyouassessthepatientagainaftergivinghertheantibiotics,hersaturationscontinuedtoworsenSheisnotspeakinginshortphrases.Thereisnoaudiblewheezehowevertherearebilateralcrepitations.Despitegivingherantibiotics,shecontinuetofeelbreathless.Theimpressionfromtheprimaryteamnowis:NeutropenicSepsis
Q5.AllofthefollowinginvestigationsarereasonabletoorderedEXCEPT(Choose1):
Bronchoscopy ColonoscopyCTThorax CoagulationProfileTransthoracicEchocardiogram
Additionally,theuseofrectalthermometers,enemas,suppositories,andrectalexamsarecontraindicatedamongHSCTrecipientstoavoidskinormucosalbreakdown(DIII).
Whileyouarerushingwithallyourbusiness,andrunningaroundinthewards,shesuddenlystopsyouandcomplainsaboutthissorethroatandcoughthatsheisveryirritatedby.Youlookedintoheroralcavity.
Q6:Whatwillyoustartheron?(Choose1)
OralbicarbonatetabletsLignocaine1%MouthwashLozengesNystatinMouthwashOralSeven Moisturing MouthwashOralfluconazole
Whileyouarerushingwithallyourbusiness,andrunningaroundinthewards,shesuddenlystopsyouandcomplainsaboutthissorethroatandcoughthatsheisveryirritatedby.Youlookedintoheroralcavity.
Q6:Whatwillyoustartheron?(Choose1)
OralbicarbonatetabletsLignocaine1%MouthwashLozengesNystatinMouthwashOralSeven Moisturing MouthwashOralfluconazole
Mdm Ang continuedtodowellinpatientunderyourcare.Shewasstartedprompty on
antibioticsandherrecoveredgradually.Intheward,shecontinuestochatwithyou.
Onelifesaved.
Q7.Inadditiontopharmacologicaltherapy,youwouldadviseallofthefollowing
EXCEPT(Choose1)
Eatonlycookedfood
Wearamaskwheneveryougoout
Limittheamountofpeoplewhovisitsyou
Isolatethepatientinanegativepressureroom
Maintaingoodoralhygiene
Mdm Ang continuedtodowellinpatientunderyourcare.Shewasstartedprompty on
antibioticsandherrecoveredgradually.Intheward,shecontinuestochatwithyou.
Onelifesaved.
Q7.Inadditiontopharmacologicaltherapy,youwouldadviseallofthefollowing
EXCEPT(Choose1)
Eatonlycookedfood
Wearamaskwheneveryougoout
Limittheamountofpeoplewhovisitsyou
Isolatethepatientinanegativepressureroom
Maintaingoodoralhygiene
XII.WhatEnvironmentalPrecautionsShouldbeTakenWhenManagingFebrileNeutropenicPatients?
Recommendations• Handhygieneisthemosteffectivemeansofpreventingtransmissionof
infectioninthehospital(A-II).• Standardbarrierprecautionsshouldbefollowedforallpatients,and
infection-specificisolationshouldbeusedforpatientswithcertainsignsorsymptoms(A-III).
• HSCTrecipientsshouldbeplacedinprivate(ie,singlepatient)rooms(B-III).AllogeneicHSCTrecipientsshouldbeplacedinroomswith.12airexchanges/handHEPAfiltration(A-III).
• Plantsanddriedorfreshflowersshouldnotbeallowedintheroomsofhospitalizedneutropenicpatients(B-III).
WHAT CAN I DO TO PREVENT?IDSA Guidelines: Neutropenic Fever
BONUSQUESTIONSMdm Ang wasofficiallydischargedfromthehospitaltheresoon
afterandshewentaboutherdailychores.Howeverwhenyouwenthomethatnight
shewasdischarge,youhadthreeseparatedreamsandthesewerethedreamsthatyou
had.Whatwouldyoudointhosesituations
Q7a:Inyourfirstdream,Mdm Ang continuedtospiketemperaturedespitebeingon
IVCefepime for4days.Whichantibioticswouldyouaddon?(Choose1)
Amikacin Azithromycin
Tamiflu Doxycyclin
Vancomycin Imipenem
Tigecycline
BONUSQUESTIONSMdm Ang wasofficiallydischargedfromthehospitaltheresoon
afterandshewentaboutherdailychores.Howeverwhenyouwenthomethatnight
shewasdischarge,youhadthreeseparatedreamsandthesewerethedreamsthatyou
had.Whatwouldyoudointhosesituations
Q7a:Inyourfirstdream,Mdm Ang continuedtospiketemperaturedespitebeingon
IVCefepime for4days.Whichantibioticswouldyouaddon?(Choose1)
Amikacin Azithromycin
Tamiflu Doxycyclin
Vancomycin Imipenem
Tigecycline
Q7b:Inyourseconddream,despiteIVCefepime andIVVancomycinfor7
days,Mdm Ang continuedtospiketemperature.Hercountsremainedlowon
dailygcsf.Whatelsewouldyoudo?(choose1)
EscalateantibioticstoMeropenem
ChangeVancomycintoDaptomycin
ChangeIVCefepime toIVTazocin
AddIVCaspofungin
StartIbruprofen
Q7b:Inyourseconddream,despiteIVCefepime andIVVancomycinfor7
days,Mdm Ang continuedtospiketemperature.Hercountsremainedlowon
dailygcsf.Whatelsewouldyoudo?(choose1)
EscalateantibioticstoMeropenem
ChangeVancomycintoDaptomycin
ChangeIVCefepime toIVTazocin
AddIVCaspofungin
StartIbruprofen
Q7c:Inyourlastdream,beforeyouwokefromallyournightmares,Mdm Ang was
notedtohaveacatheter-relatedlineinfection.Whicharethemicroorganisms,if
growingfromtheline,doNOTrequireyoutoremovetheline?(Choose1)
Staphylococcusaureus
Pseudomonasaeruginosa
Candida
Staphylococcushaemolyticus
Mycobacteria
Q7c:Inyourlastdream,beforeyouwokefromallyournightmares,Mdm Ang was
notedtohaveacatheter-relatedlineinfection.Whicharethemicroorganisms,if
growingfromtheline,doNOTrequireyoutoremovetheline?(Choose1)
Staphylococcusaureus
Pseudomonasaeruginosa
Candida
Staphylococcushaemolyticus
Mycobacteria
Recommendation■ Differentialtimetopositivity(DTP)>120minofqualitativebloodculturesperformedonspecimens
simultaneouslydrawnfromtheCVCandaveinsuggestsacentralline–associatedbloodstreaminfection(CLABSI)(A-II).
■ ForCLABSIcausedbyS.aureus,P.aeruginosa,fungi,ormycobacteria,catheterremovalisrecommendedinadditiontosystemicantimicrobialtherapyforatleast14days(A-II).Catheterremovalisalsorecommendedfortunnelinfectionorportpocketsiteinfection,septicthrombosis,endocarditis,sepsiswithhemodynamicinstability,orbloodstreaminfectionthatpersistsdespite>72hoftherapywithappropriateantibiotics(A-II).
■ FordocumentedCLABSIcausedbycoagulase-negativestaphylococci,thecathetermayberetainedusingsystemictherapywithorwithoutantibioticlocktherapy(B-III).
■ Prolongedtreatment(4–6weeks)isrecommendedforcomplicatedCLABSI,definedasthepresenceofdeeptissueinfection,endocarditis,septicthrombosis(A-II)orpersistentbacteremiaorfungemiaoccurring>72haftercatheterremovalinapatientwhohasreceivedappropriateantimicrobials(A-IIforS.aureus,C-IIIforotherpathogens).
IDSA Guidelines: CENTRAL LINE ASSOCIATED BLOOD STREAM INFECTION
LEARNING POINTSSKILLS
1. Evidence-basedmedicine:touseyourclinicalreasonining andunderstandofevidence
2. Synthesisofinformationandgeneratingalistofproblems
3. Approachtoclinicalquestions
CONTENT
1. NeutropenicSepsis
2. INFECTIONSINANIMMUNOCOMPROMISEDHOST