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bacteria Identification Importantfeatures

diseases Treatment

S.pyogenes(groupAstreptococci)

Bacitracintest-sensitive,unlikeotherbetahemolytics.

-Betahemolytic-Ccarbohydrate-Mprotein-lipoteichoicacid-fivetoxins-threeinvasiveenzymes.

pharyngitisandcellulitis(softtissueinfection).Impetigo,necrotizingfasciitis,streptococcaltoxicshocksyndrome,glomerulonephritis,rheumaticfeverscarletfever.

PenicillinGoramoxicillin.Mild->oralpenicillinV.Penicillin-allergicpatients1)erythromycin2)Clindamycin.

S.agalactiae(groupB)

ColordetectionofHippuratehydrolytesproducedbyitshydrolysis

-Betahemolytic-bacitracinresistant.-Mprotein-Ccarbohydrate

neonatalsepsisandmeningitisbecauseitabnormallycolonizesthebirthcanal.

PenicillinGOrampicillin(givenorally,itisn’teffectiveineradicatingtheorganism)

Enterococcusfaecalis(groupD)(also,enterococcusfaecium)

- growthonbile-esculinagar.- resistanttopenicillin.

-classicalentericG+vecocci- cangrowinhypertonic6.5%saline,theysurvivebilesalt.- resistanttopenicillinG.

Opportunistically urinarytractinfections,biliaryinfectionsandendocarditis.StrongerandmoreinfectionsthanS.bovis,becauseE.faecalisishardier.

synergisticcombinationofpenicillinandanaminoglycoside(e.g.,gentamicin)-vancomycin,butVREshaveemerged.

S.bovis(groupD)

-sensitivetopenicillinG.-growthonbileesculin.

-notenterococcal-inhibitedby6.5%NaCl

Opportunisticallyendocarditis

PenicillinG

S.pneumoniae(majoralphahemolytic,nolancefieldgrouping_

Sensitivetooptochin,bilesolublecolonies.

Alphahemolytic Queenofseriousdiseases.-1)pneumonia2)bacteremia3)meningitis,and4)URTI

Penicillinv(mild)penicillinG(severe).Erythromycin,azithromycin(pen.Allergicpatients)Vancomycin(pen.resistance)

Viridansgroup(sameaspneumococci)

Oppositeofpneumococci.

Alphahemolytic(viridans=green)

Mostcommoncauseofendocarditis

prolongedpenicillintreatment(endocarditis)

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First,importantpropertiesofstreptococci:

Second,classification:

(thisisStreptococcuspyogenes,noticethearrangement)

streptococci(especiallythoseofmedicalimportance)aresomany,that’swhyweuseaclassificationsystemtodistinguishbetweenthemandwediagnosediseasebyclassificationratherbyspecies.(E.g.wesay:apatientisinfectedwithgroupAstreptococcusratherthansayingstreptococcuspyogenes).

Wehavetwogroupingmethods:A. modeofhemolysis.Accordingtothiswehavethreetypes:

Betahemolytic

Alphahemolytic

Gammahemolytic

β-Hemolyticstreptococciformaclearzonearoundtheircoloniesbecausecompletelysisoftheredcellsoccurs.β-Hemolysisisduetotheproductionofenzymes(hemolysins)calledstreptolysinOandstreptolysinS(willpassin“Pathogenesis”later).

α-Hemolytic streptococci form agreenzonearoundtheircoloniesasaresultof incomplete lysisofredbloodcells.Thegreencolorisformedwhenhydrogenperoxideproducedbythebacteriaoxidizeshemoglobin(redcolor)tobiliverdin(greencolor).

Somestreptococciarenon-hemolytic(γ-hemolysis).

B. Lancefield(abacteriologist)grouping(aSerologicalidentification)bythisweclassifyonlybetaandmixedhemolytics(caneitheruseαorβhemolysis)togroupsfromAtoUaccordingtoacarbohydratecomponentintheircellwall.

Inthepreviouslecturewehavetalkedaboutstaphylococci,whicharethefirstgrampositivecocciofmedicalimportance.Today,we’lltalkabouttheothergram-positivecocci,Streptococci.Therewillbevariationsinorderfromtheslides.

• StreptococciareGrampositivecocciarrangedinchains(alongthesameaxis)orpairs(especiallypneumoccus).TheyareinvaderswhileStaph.arenesters.

• Allstreptococciarecatalase-negative,unlikestaphylococciwhicharecatalase-positive.

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TheonesthatholdthemostmedicalimportanceareA,B&D(thosearehumanpathogens).themajoralphahemolyticfamiliesarenotgroupedthisway.

Onlythosewhicharecoagulasenegativeandcatalasenegativearegrouped

Amethodusedtoestablishgroupingislatexagglutinationtest.Onthelatexwehavewellscontainingantibodiesthatcanreacttotheserumorthebacteriawehave.

Theantibodiesareboundonlatex,onceyoupasstheserumonthelatex(wells)beads(clumps)willforminthewellwhereantibodiesreactwiththeirantigen(seeninB).Iftheantigenisnotpresenttothatspecificantibodyonthelatex,nobeadsform(D).

V. Importanttable:

Bothutilizebileesculin

Notesonthetable:v Thistablegivesusallthegroupswecareabouttogether.Thestreptococciare

groupedaccordingtohemolysisfirstintoalpha,betaandmixedhemolytics,thensomearefurthergroupedbyLancefieldgroupingintoA,BandDgroups.

v ifwegetabetahemolyticbacteriafromthegutit’susuallyGroupDstreptococci(guttypestreptococci)

v Viridansgroupincludesmanybacteria,likeS.mitis,S.mutans,S.sanguinis,S.salivarius,S.gordonii,S.anginosus,S.milleri.

-RememberhowwesaidthatonewouldgetpartialimmunitywhentheymeetStaphylococcus?Thecasewithstreptococcusisbothbetterandworse.Betterbecausewegetfullimmunityagainstastrainofstrepwemet.However,AntibodytoMproteinprovidesONLYtype-specificimmunity.AndTherearesomanyserotypesthatwecan’tpossiblybeimmunetoalloftheminourlife.Forexample;thereare86typesofpyogenes.Whichaidsintheoccurrenceofimmunogenicdiseases(keepinmindthemlater).

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Unlikestaphylococci,whereallthefameandfortunewereofS.aureus,herethefameandfortunearedividedtothethreemostviciousgroups:

1) GroupA-βhemolyticstreptococci(S.Pyogenes)becauseithasallthemechanismsofevilaction,toxigenic,immunogenic,pyogenic.

2) Entericstreptococci(E.Faecalis)becausetheydevelopanti-microbialresistance.theyinhabitthecolonandtheyareexposedtosomanyantimicrobials,sotheydevelopresistanceeventually.

3) S.pneumoniae(pneumococci),becauseitcausesmostoftheseriousdiseaseswhichwillbediscussedseparately.

Details:

Betahemolyticstreptococci:

ThefirstonegroupAknownasStreptococcipyogenes,theotheroneisgroupBknownasstreptococcusagalactiae.

Differentiationbetweenthetwobetahemolytics:weuseBacitracintest,whichisanantibiotic,theonesensitivetoitisthepyogenes,theotheroneisresistant.

Therearetwoimportantantigensthataremostprominentinβ-hemolyticstreptococci:• (1)Ccarbohydratedeterminesthegroupofβ-hemolyticstreptococci.(usedforgrouping).Itislocatedinthecellwall,anditsspecificityisdeterminedbyanaminosugar.

• (2)MproteinisthemostimportantvirulencefactoranddeterminesthetypeofgroupAβ-hemolyticstreptococci.(usedfortyping;furtherclassificationofβhemolytic).Itprotrudesfromtheoutersurfaceofthecellandinterfereswithingestionbyphagocytes(i.e.itisantiphagocytic).

Streptococcuspyogenes(groupA):

Diseases:groupAstreptococci(S.pyogenes)istheleadingbacterialcauseofpharyngitis(presentswithexudateonthetonsils)andcellulitis(skin/softtissueinfections),sepsis,endometritisandthesearethepyogenicdiseases,italsocausesimpetigo(characteristic:honeycoloredcrustedlesionsonskin)andlymphangitiscanoccur.AndNecrotizingfasciitisandstreptococcaltoxicshocksyndromeandscarletfeverwhicharetoxigenicdiseases.UnlikeStaph.aureus,whichhasanassociationwith

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Kawasakidisease(butit’snotwellestablished).Streptococcuspyogeneshaswellestablishedimmunogenicdiseases,rheumaticfeverandacuteglomerulonephritis.

• Theypossesstwofactorsthatallowthemtoadheretopharyngealepithelium:pilicomposedoflipoteichoicacidandtheMprotein.• Manystrainshaveahyaluronicacidcapsulethatisantiphagocytic

MproteinisthemainantiphagocyticcomponentofS.pyogenes(itpreventscomplementactivation).

Mproteinistheimmunogenicstructurethatcausesthetwoimmunogenicdiseases.Thereareapproximately80serotypes(bacterialantigens)basedontheMprotein,hence,youcangetmultipleinfectionswithS.pyogenesfromdifferentserotypes.

Imaginethattherearefewofthemthatcausepharyngitis,antibodiesproducedagainstthosearecrossreactivetotheheart,theseantibodiesendupattackingtheheartandjoints,causingRheumaticfever,theseserotypesareknownasRheumatogenic.

Otherserotypesthatcauseskininfections,induceABsproductionthatarecrossreactivetothekidney,theseattackthekidneycausingaconditioncalledglomerulonephritis,theseareknownasnephritogenic.(Mproteintype49causesAGNmostfrequently)

->Ittakestwoweeksforthetiterofantibodiesagainstthesebacteriatorisetoalevelhighenoughtocausetheseimmunogenicdiseases,sowecan’tdetectbacteriainthesecasesbutwelookfortheantibodies.(post-streptococcalinfections).

->mostly,pediatricpatientsareaffectedbytheseconditions,becausetheyare morepronetostreptococcalinfections.

Transmission:S.pyogenesisfoundontheskinandintheoropharynxinsmallnumber,that’swhywecan’tdifferentiatebetweenitandthenormalflorabyswabundermicroscopeinvestigation(cannotbevisuallydistinguished).TransmissionbySkintoskininteraction.However,stainedsmearsfromskinlesionsorwoundsthatrevealstreptococciarediagnostic

Pleasenotethattheinitialinfectiondidnotinvolve theorgansaffectedlaterbyimmunogenic diseases,rathertheinflammation inducedbytheantibodiescausedthesymptomsintheseorgans.i.e.thebacteriadonotinfecttheheartorjointsinthecaseofrheumaticfever,it’stheantibodiesproducedagainstthebacteriainthepharynx thatcausedtheinflammation intheheartandjoints.

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Pathogenesis:

Noticehowallofthemhavepyogenicfeatures,meaningtheycausediseaseinanareawheretheyinfect.However,pyogeneshasmorewaysofinducingbadeffects.

Note:thetablehasinformationaboutotherbacteria,buttheonethatatemostofthepiehereisS.pyogenes.

Itcausesdiseasebythreemechanismswementionedbefore:1) pyogenicinflammation.Inducedlocallyatthesiteoftheorganisms’presencelikeinthecaseofcellulitisorpharyngitisOrsystematicallyiftheorganismreachesthebloodlikeinthecaseofsepsis.

2) exotoxinproduction.Cancausespreadsystemicconditions,inplacesfarfromtheorganism.Likescarletfeverortoxicshock.Still,instreptococcaltoxicshockbacterialcultureismostlypositivebecausetheorganismispresentintheblood.3)Immunogenic,whichisabouttheantibodies’crossreactionwediscussedbefore.Theymightcauseinflammation,BUTtherearenoorganismsfoundin

Botharecasesofpharyngitisbuttheoneontherighthasexudateandpus-thewhitisharea-andthisisacharacteristicofgroupAsrep.Infection.Noticetheoneontheleftisjusthighlyinflamedandreddened (hyperaemia)withoutthepus,thisismostprobablyaviralinfection.

Veryimportanttable

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thosecases,becausemostlythey’repostinfectioncomplications,thatwedetectbyfindingantibodiesagainstthebacteria,nottheprimarybacterialcause.

ApartfromitsmechanismsS.pyogenesproducesmanyenzymesthathelpsitinvade,insteadofnesting.Theseare:

(1)Hyaluronidase,thisdegradeshyaluronicacid,whichisthegroundsubstanceofsubcutaneoustissue(helpswithinvasion),thisiswhyHyaluronidaseisknownasspreadingfactor.(flesheatingbacteria)

(2)Streptokinase(fibrinolysin)activatesplasminogentoformplasmin,whichdissolvesfibrininclots,thrombi,andemboli.Itcanbeusedtolysethrombiinthecoronaryarteriesofheartattackpatients.(nowweusealteplasetodissolveclots)

(3)DNase(streptodornase)degradesDNAinexudatesornecrotictissuebecausethere’ssomuchDNAexitingcausingDNAhindrance.(anti-DNaseBisusedtodetectpreviousskininfectionwithGAS(groupAstreptococcus).

Toinducethetoxigeniceffectwediscussed,S.pyogenesproducesfivetoxins:(refertoslidesforpictures)(1) Erythrogenictoxincausestherashseeninscarletfever(erythemamarginatum)whichhasacharacteristicstrawberrytongue.ItsmechanismofactionissimilartothatoftheTSST(toxicshocksyndrometoxin)ofS.aureus(actsasasuperantigen).(skinandtonguearemostlyaffected).(2) StreptolysinOisahemolysin–breaksdownRBCsforiron.It’sOxygenlabile.Itisantigenic-importantinimmunogenicdiseases-.AntibodytostreptolysinO(anti-ASO)developsaftergroupAstreptococcalinfections.Thetiteroftheseantibodiescanbeimportantinthediagnosisofrheumaticfever.(rememberwesaidweuseABstiterfordiagnosis).

(3) StreptolysinSisahemolysin.(oxygenstable).(4) PyrogenicexotoxinAthetoxinresponsibleformostcasesofstreptococcaltoxicshocksyndrome.IthasthesamemodeofactionasTSST.(invadingtheblood).(5) ExotoxinBisaproteasethatrapidlydestroystissueandisproducedinlargeamounts

Weknowthatantibodiestiterpeaksaround twoweeksafterinfection,soifakidpresentedwithsymptomsofrheumaticfeverandyoudoantibodiesdiagnosisandfindtheantibodiesagainststreptolysinO,thisisanindicationofpreviousinfectionwithGASe.g.pharyngitis.

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bysomestrainsofS.pyogenes,theso-called“flesh-eating”streptococcithatcausenecrotizingfasciitis

Moreaboutimmunogenicpoststreptococcalnon-suppurativediseases:

Acuteglomerulonephritis:

Itoccurs2-3weeksafterskininfection,becauseitrequiresantibodyproduction.

• Occursmostlyinchildren

Themoststrikingclinicalfeaturesare:• hypertension(almostalwaysaveryoddfindinginchildren)• edemaoftheface(especiallyperiorbitaledema)andankles(lossofprotein),puffykid.•“smoky”urine(duetoredcells,orproteinintheurine)

• Mostpatientsrecovercompletely,howevertheyarestillpronetodevelopthisagainifreinfectionwithstreptococcihappens,anditgivesthesameeffects.

• Itcanbepreventedbyearlyeradicationofnephritogenicstreptococcifromskincolonizationsitesbutnotbyadministrationofpenicillinaftertheonsetofsymptoms,becausethecauseofthesesymptomsisn’ttheorganism,buttheaftermathofitbeingthere,theantibodyisalreadymade.

Acuterheumaticfever:

Approximately2weeksafteragroupAstreptococcalinfection—usuallypharyngitis.characterizedby:

1- Fever,

2- Migratorypolyarthritis(hisknees,orhiselbowshurtsuddenly)

3- Carditis,maydevelopandit’sthemostserious,asdamagetothemyocardialandendocardialtissue,especiallythemitralandaorticvalves,canresultinvegetation(abnormalgrowththatmaycontaindebris)onthevalves.4- Uncontrollable,spasmodicmovementsofthelimbsorface(chorea)mayalsooccur.

->acuterheumaticfeverpresentswithcirclesoferythemawithcentralclearing.

Thesecomplicationscanbepreventedbyprompttreatment(within8days)oftheorganisminfectingthepatient–beforeproducingantibodies.

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unlikepoststrepAGN,itisGREATLYexacerbated(madeworse)byrecurrenceofstreptococcalinfections.Eachtimethepatientgetsinfected,itgetsmoreandmoreexaggerated,causesmoredamagetotheheart.

topreventfurtherpain,ifthepatientisinfectedagain,wegiveprophylacticsfortherestofhislife.(prophylacticsaremedicationsusedforpreventingadiseaseorinfection,they’regivenoncesignsorsymptomsofearlyinfectionoccur).

mostcasesofpharyngitiscausedbygroupAstreptococcioccurinchildrenage5to15years,andhencerheumaticfeveroccursinthatagegroup.

Treatment:• GroupAstreptococcalinfectionscanbetreatedwitheitherpenicillinGoramoxicillin

• InmildgroupAstreptococcalinfections,oralpenicillinVcanbeused.

• Inpenicillin-allergicpatients,erythromycinoroneofitslong-actingderivatives(e.g.,azithromycin)canbeused.However,erythromycinresistantstrainsofS.pyogeneshaveemerged.

• Clindamycincanalsobeusedinpenicillin-allergicpatients.

*Remember:immunogenicdiseases(AGN,RF)can’tbetreatedwithantibioticsbecausetheantibodiesarealreadyproduced,theorganismismostprobablygone.Prevention:RheumaticfevercanbepreventedbyprompttreatmentofgroupAstreptococcalpharyngitiswithpenicillin.ThereisnoevidencethatpatientswhohavehadAGNrequiresimilarpenicillinprophylaxis.1)Insusceptiblepeople(previousinfection)Preventionofstreptococcalinfections(usuallywithbenzathinepenicillinonceeachmonthforseveralyears).

2)Inpatientswithdamagedheartvalveswhoundergoinvasivedentalprocedures,endocarditiscausedbyviridansstreptococcicanbepreventedbyusingamoxicillinPREoperatively.AgainPREOPERATIVLEYNote:Toavoidunnecessaryuseofantibiotics,itisrecommendedtogiveamoxicillinprophylaxisonlytothosepatientswhohavethehighestriskofsevereconsequencesfromendocarditis(e.g.,thosewithprostheticheartvalvesorwithpreviousinfectiveendocarditis)andwhoareundergoinghigh-riskdentalprocedures,suchasmanipulationofgingivaltissue.

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Streptococcusagalactiae:(groupB)Diseases:Streptococcusagalactiae(groupBstreptococcus)istheleadingcauseofneonatalsepsisandmeningitis;thishappensinwomenwhoarecolonizedwithGBS-becausethefirstbacteriathatababygetsexposedtoarethebacteriainthebirthcanal-andhavehadPROM(prolongedruptureofthemembrane-thesackofthebaby),thedelayinbirthandtheexposureofthefetuspredisposesthemtotheinfection.Itcausesneonatalpneumonia.->GBSisstillcapableofcausinginfectionsinadults(suchaspneumonia,endocarditis,arthritis,cellulitis,andosteomyelitis)DiabetesisthemainpredisposingfactorforadultgroupBstreptococcalinfections(howcome?)-therearetheories,themostacceptedisthattheriseofsugarinbloodreducesthefunctionoftheimmunesystem,alsocausesreductioninbloodflow(recruitmentofWBCs)andnervedamage(alsopreventsproperimmunefunction)

Testing:It’sbacitracinresistant,sowefurtherconfirmit’sBbyHippuratetest(ithydrolyzesitintotwomolecules(glycineandbenzoicacid)thatcanbecolordetected.(itturnsblue)(CAMPtest):theproductionofaproteinthatcausesenhancedhemolysisonsheepbloodagarwhencombinedwithβ-hemolysinofS.aureus

Transmission:Itabnormallycolonizesthefemalegenitaltract.(occursinthevaginaandcolon)Postpartumendometritisalsooccurs(infectionoftheliningofuterusafterbirth)whyafterbirth?Thisisaskinpathogen,openingoftheusuallyclosedenvironmentoftheuterusduringbirthandmanipulationbyhospitalstaff(whoarecolonizedwiththesebugs).

Pathogenesis:GroupBstreptococcihaveapolysaccharidecapsulethatisantiphagocytic,andanticapsularantibodyprotective.PathogenesisbygroupBstreptococci(S.agalactiae)isbasedontheabilityoftheorganismtoinduceaninflammatoryresponseunlikeS.pyogenes,nocytotoxicenzymesorexotoxinshavebeendescribed,andthereisnoevidenceforanyimmunologicallyinduceddisease(notoxigenicityandnoimmunogenicinduceddiseases).

Treatment:ThedrugofchoiceforgroupBstreptococcalinfectionsiseitherpenicillinGorampicillin,SomestrainsmayrequirepenicillinGwithaminoglycosidetoeradicatetheorganism.

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Prevention:AsforGBS,theincidenceofneonatalsepsiscanbereducedbyacombinationoftwoapproaches:

• (1)ScreeningofALLpregnantwomenat35to37weeks’gestationbydoingvaginalandrectalcultures(RST).Ifculturesarepositive,thenpenicillinG(orampicillin)shouldbeadministeredintravenouslyatthetimeofdelivery.

• (2)Ifthepatienthasnothadculturesdone,thenpenicillinG(orampicillin)shouldbeadministeredintravenouslyatthetimeofdeliverytowomenwhoexperienceprolonged(longerthan18hours)ruptureofmembranes1,whoselaborbeginsbefore37weeks’gestation2,orwhohaveafeveratthetimeoflabor3.Ifthepatientisallergictopenicillin,eithercefazolinorvancomycincanbeused.

• OralampicillingiventowomenwhoarevaginalcarriersofgroupBstreptococcidoesnoteradicatetheorganism.

Mixedhemolyticstreptococci(groupD):Wearestudyingtwo:a. enterococci->classicalentericGram-positivecocci,e.g.Enterococcusfaecalis&Enterococcusfaecium.

b. non-enterococci->e.g.,S.bovis.

Wedifferentiatebetweenthetwoby2mechanisms:1stNaCl6.5%hypertonicsaline,enterococcicansurviveit,whileS.boviscan’t.

2ndpenicillin,enterococcusisresistantwhileS.bovisissensitive.Theybothcangrowonbileesculinandturnitblack.

🌸 Their hemolysis is variable, some are beta, most are alpha andothersarenon-hemolytic.

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EnterococcusFaecalis:Enterococcus,isahardyorganism,it’stheonlygrampositivewefindinthecolon,

becauseit’stheonlyGrampositivehardyenoughtosurvivetheharshenvironmentofthestomachandthebile.EnterococcusfaecalisisanimportantcauseofHospital-AcquiredUrinaryTractInfections(nosocomialinfections)andendocarditis,normallyitcausesnodiseasesbecauseit’spartofthenormalflora.It’sanopportunisticbacterium,thatgetsnaughtyifitreachestheblood.Itcausesurinary,biliary,andcardiovascularinfections.Enterococcialsocauseendocarditis,particularlyinpatientswhohaveundergonegastrointestinalorurinarytractsurgeryorinstrumentation,thisiswhytheyarenotcommon,wedoalotmoredentalproceduresandintroduceviridansgroupthatwedoGIorUTsurgery.Theyalsocauseintra-abdominalandpelvicinfections,typicallyincombinationwithanaerobes(thesameasotherstreptococci,ifgiventheaccessandchancetheywillcauseabcess)

• HAUTIsareduetotheuseofcatheterscombinedwithbedpans-contamination• Thus→Indwellingurinarycathetersandurinarytractinstrumentationareimportantpredisposingfactors.

->About10%ofendocarditiscasesarecausedbyenterococci,butanyorganismcausingbacteremiamaysettleonalreadydeformedvalves.Transmission:•enterococciandanaerobicstreptococciarelocatedinthecolonTreatment:sinceEnterococciaretough,weuseasynergisticcombinationofpenicillinandanaminoglycoside(e.g.,gentamicin)tokillit.Vancomycincanalsobeused,butvancomycin-resistantenterococci(VRE)haveemergedandbecomeanimportantandmuchfearedcauseoflife-threateningnosocomialinfections.• Enterococcalendocarditiscanbeeradicatedonlybyapenicillinorvancomycincombinedwithanaminoglycoside.

• Enterococciresistanttomultipledrugs(e.g.,penicillins,aminoglycosides,andvancomycin)haveemerged.

• ResistancetovancomycininenterococciismediatedbyacassetteofgenesthatencodetheenzymesthatsubstituteD-lactateforD-alanineinthepeptidoglycan.ThesamesetofgenesencodesvancomycinresistanceinS.aureus

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• Atpresent,twodrugsarebeingusedtotreatVREinfections:linezolid(Zyvox)anddaptomycin(Cubicin).

Streptococcusbovis:

(NonenterococcigroupD)→theclassichumanpathogenofthisgroupisS.bovis,cancausesimilarinfectionstotheEnterococci,buttheyarenotstrongasEnterococci.

->S.boviscausesendocarditis,especiallyinpatientswithcarcinomaofthecolon.ThisassociationissostrongthatwhenwefindpatientswithS.bovis,bacteremia,orendocarditis,thesepatientsshouldbeinvestigatedforthepresenceofcoloniccarcinoma.Treatment:penicillinG.

Alphahemolyticstreptococci:Thesearetwo,Streptococcuspneumoniaandtheviridansgroup,wedifferentiatebetweenthetwoby,1)bilesolubility,wherepneumococciarebilesolubleandviridansaren’t2)optochinsensitivity,wherepneumococciaresensitiveandviridansaren’t.

PathogenesisbyS.pneumoniaeandtheviridansstreptococciisuncertain,asnoexotoxinsortissue-destructiveenzymeshavebeendemonstrated.Streptococcuspneumonia:lancet-shapedcocci(areovalwithsomewhatpointedendsratherthanbeinground موثلك مأ تاراظن ):arrangedinpairs(diplococci)orshortchains

Diseases:1) pneumonia(symptoms:suddenchill,fever,cough,shortnessofbreath,andpleuriticpain-chestpainthatincreaseswithchestmovement-breathing).• Sputumisaredorbrown“rusty”color,capsulatedbacteriacausessputumcoloration.Bacteremiaoccursin15%to25%ofcases.

Spontaneousrecoverymaybeginin5to10daysandisaccompaniedbydevelopmentofanticapsularantibodies.

2) bacteremia3)meningitis,and4)URTI(upperrespiratorytractinfections)-suchasotitismedia,mastoiditis,andsinusitisbymigrationthroughtheblood.5)sepsisinsplenectomizedindividuals(theycan’tgetridofcapsulatedbacteria).6)conjunctivitis,especiallyinchildren.

Virulencefactors:

1)ThemainvirulencefactorofS.pneumoniaeisitsantiphagocyticpolysaccharidecapsule1whichhas85antigenicallydistincttypes.(thussplenectomypatientscantclearthisorganism).Withtype-specificantiserum,capsulesswell(quellungreaction),andthiscanbeusedtoidentifythetype

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Thiscapsuleshieldsthebacteriaasitmoveswiththebloodto:

thebraincausingmeningitis,lungcausingpneumonia,andtheURTIswementioned.

2)IthasanenzymethathelpsitbreakdownIgA(IgAprotease)2,thatalongwithcapsuleandteichoicacidhelpinitsattachmenttomucosalsurfaces,causinginfection.

3)Teichoicacid3inthecellwallistheC-substance(alsoknownasC-polysaccharide),towhichCRP(C-reactiveprotein)reacts,andthisiswhywe*usethesebacteriatomeasureCRPindiagnosingacuteinflammationandheartdisease(c-substanceholdsmedicalimportance)**anelevatedCRPappearstobeabetterpredictorofheartattackriskthananelevatedcholesterollevel.

4)Pneumolysin4,thehemolysinthatcausesα-hemolysis,maycontributetopathogenesis.

5)Lipoteichoicacid5:complementactivator,itinducesinflammatorycytokineproductionwhichcontributestotheinflammatoryresponseandtothesepticshocksyndromeinsomecases

Factorsthatlowerresistanceandpredisposepersonstopneumococcalinfection:• INCLUDE factors that reduce mucus clearing or factors that decrease immunereaction),accumulationofmucusisahappyevent,ifithappenspneumococcihappilycausepneumonia→ THISISTHEMOSTIMPORTANTPIECEOFINFORMATION

(1) anythingthatcandepressthecoughreflux:alcoholordrugintoxicationorothercerebralimpairment(theydon’tcough,theydon’tclearmucous,itaccumulatesandpneumoniahappilyhappens)

(2) abnormalityoftherespiratorytract(e.g.,viralinfections),poolingofmucus,

bronchialobstruction,andrespiratorytractinjurycausedbyirritants(whichdisturbtheintegrityandmovementofthemucociliaryblanket)allpreventclearingofmucusandpredisposetopneumoniacausedbypneumococcus.

(3) abnormalcirculatorydynamics(e.g.,pulmonarycongestionandheartfailure)willcongestthebloodinthelung,increasepulmonarysecretions→pneumococcuscomes.

(4)splenectomy(capsule,reducesimmunity)andcertainchronicdiseasessuchassicklecellanemiaandnephrosis,patientswithsicklecellanemiaauto-

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infarcttheirspleen,becomefunctionallyasplenic,andarepredisposedtopneumococcalsepsisRemember:nospleen,noclearingofcapsulatedbacteria!

(5)Traumatotheheadthatcausesleakageofspinalfluidthroughthenosepredisposestopneumococcalmeningitis

Transmission:

• Humansarethenaturalhostsforpneumococci;thereisnoanimalreservoir.

• Becauseaproportion(5%–50%)ofthehealthypopulationharborsvirulentorganismsintheoropharynx,pneumococcalinfectionsarenotconsideredtobecommunicable(ithappensfromyourownflora)

�� ھیف لمعأ وش تفرع ام غارف

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Labdiagnosis:• Cultureofcerebrospinalfluidisusuallypositiveinmeningitis(bydetectingitscapsularpolysaccharideinspinalfluidusingthelatexagglutinationtest).

• Arapidtestdetectsurinaryantigen(C-carbohydratenotthecapsule)forthediagnosisofpneumococcalpneumoniaandbacteremia.• Becauseoftheincreasingnumbersofstrainsresistanttopenicillin,antibioticsensitivitytestsmustbedoneonorganismsisolatedfromseriousinfections

treatment:

• standardantibiotic:penicillin(severeinfections)anderythromycin(ifsensitivetopenicillin),penicillinV(mildinfections),althoughsignificantresistancetopenicillinshasemerged• Afluoroquinolonewithgoodantipneumococcalactivity,suchaslevofloxacin,canalsobeused.• Anincreasingpercentageofisolatesshowhigh-levelresistance,whichisattributedtomultiplechangesinpenicillinbindingproteins(insteadofproducingβ-lactamase)• Vancomycinisthedrugofchoiceforthepenicillinresistantpneumococci,especiallyforseverelyillpatients.• Ceftriaxoneorlevofloxacincanbeusedforlessseverelyillpatients(weuseitifwesuspectpneumococcalinfection,especiallyinkids(preventivemeasure)

Prevention:

• Pneumococciaretheonlybacteriaoftheoneswementionedthathaveavaccine.

• Specificantibodytothecapsuleformsandopsonizestheorganism,facilitatesphagocytosis,andpromotesresistance.Weusethattogiveabacterialpolysaccharidevaccine,thatgivesimmunityagainstS.pneumoniae.

•Themortalityrateofpneumococcalinfectionsishighinimmunocompromised(especiallysplenectomized)patientsandchildrenundertheageof5years.Suchpersonsshouldbeimmunizedwiththe13-valentpneumococcalconjugatevaccine(Prevnar13).• Theimmunogeninthisvaccineisthepneumococcalpolysaccharideofthe13most

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prevalentserotypesconjugated(coupled)toacarrierprotein(diphtheriatoxoid).Theunconjugated23-valentpneumococcalvaccine(Pneumovax23)shouldbegiventohealthyindividualsage50yearsorolder.

• Thesevaccinesaresafeandeffectiveandprovidelong-lasting(atleast5years)protection.

Asecond‘’booster’’doseisrecommendedfor•(1)peopleolderthan65yearswhoreceivedthevaccinemorethan5yearsagoandwhowereyoungerthan65yearswhentheyreceivedthevaccine,and•(2)peoplebetweentheagesof2and64yearswhoareasplenic,infectedwith(HIV),receivingcancerchemotherapy,orreceivingimmunosuppressivedrugstopreventtransplantrejection.

Viridansgroup:

• Severalspeciesthatareusuallycommensal(nonpathogensinimmunecompetentpatients)butareopportunisticinimmunecompromisedpatients.

• Viridansstreptococci(e.g.,S.mutans,S.sanguinis,S.salivarius,andS.mitis)arepartofthenormalfloraofthehumanpharynxandintermittentlyreachthebloodstreamtocauseinfectiveendocarditis(majorcause).• S.mutans(oneofthegroup)synthesizespolysaccharides(dextrans)thatarefoundindentalplaqueandleadtodentalcaries• Biofilmformationandfermentationofsugarsandproductionofacidsisthemainmechanismthatcausesdestructionofenamel,meansit’sinfectingdeeper.

Poordentalhealth->potentialheartproblem.

Transmission:ViridansstreptococciandS.pneumoniaearefoundchieflyintheoropharynx.

• TheyTYPICALLYenterthebloodstream(bacteremia-bacteriainblood)fromtheoropharynxafterdentalsurgery,eventuallyreachingtheheart.

Pathogensisofendocarditis:Oncethesebacteriagetintotheblood,theyhitandsticktothemarginsofthevalves(inthecaseofviridansbyproducingglycocalyx;astickysugarcoattoformbiofilm),inlargenumberstheyprecipitateonthevalvesandstarteatingthevalvulartissuearoundthem,thuscausesfailingofthevalves->heartsymptomspresentation.

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• Signsofendocarditis:arefever(teichoicacidinducesinflammatoryreaction),heartmurmur(vegetationanddestructionofheartvalves),anemia,andembolicevents(emboliintheblood.Emboliarelikeaballofbacteriathatformsonthemarginsthendissociatesandtravelswiththeblood)thatcausesymptomssuchassplinterhemorrhages,subconjunctivalpetechialhemorrhages,andJanewaylesions.• Thevegetationoftheheartvalvesis100%fatalunlesseffectivelytreatedwithantimicrobialagent(prolongedpenicillintreatment.).

->Viridansstreptococci,especiallyS.anginosus,S.milleri,andS.intermedius,arealsoacauseofbrainabscesses.asmentionedbeforetheseareusuallymulti-pathogenicandareseenoftenincombinationwithmouthanaerobes(amixedaerobic–anaerobicinfection).dentalsurgeryprovidesaportalfortheviridansstreptococciandtheanaerobesintheoropharynxtoenterthebloodstream(bacteremia)andspreadtothebrain.

Insummary:thesearethegeneralmodesofpathogenesis:viridans=biofilm,pneumococcus=capsule,GAS=exotoxinsandinvasiveenzymes,GBS=inflammatory

Therapidsteptest:

WeuseitalotforgroupAfastidentification,toprescribetheappropriateantibioticfast.

Therapidtestdetectsbacterialantigensinathroatswabspecimen.Inthetest,specificantigensfromthegroupAstreptococciareextractedfromthethroatswabwithcertainenzymesandarereactedwithantibodytotheseantigensboundtolatexparticles

->Thespecificityofthesetestsishigh,butthesensitivityislow(i.e.,false-negativeresultscanoccur)

->ArapidtestisalsoavailableforthedetectionofgroupBstreptococciinvaginal&rectalsamples.ItdetectstheDNAoftheorganism,andresultscanbeobtainedinapproximately1hour.

Lookatthefirstthree,thefirst(control)lineispresent,anditshouldalwaysbethere.Itmeansthatitworks,ifnot*likesample4and5*,it’snotworking.

Evenifthesecond(test)lineisfaint,it’sstillconsideredpositive!

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