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Chapter5BacterialinfectiousdiagnosisandpreventionDiagnosisforPathogenicBacteriumSignsandsymptomsvaryaccordingtothesiteandseverityofinfection.Diagnosisrequiresacompositeofinformation,includinghistory,physicalexamination,radiographicfindings,andlaboratorydata.

laboratoryAssaysMorphologicalassaysLightorelectronmicroscopyIsolationanddifferentiationSerologicalassaysAntigen-antibodyassaysMolecularassaysMicroorganism’sgene(DNA&RNA)DiagnosisofEtiology:

Goldenstandardistodetectthepathogenicbacterium

SpecimenCollectionandProcessingObtainspecimensfromtheinfectedsiteAvoidcontaminationfromthenormalfloraTransportingandstoringcorrectlyBeforeantimicrobialdrugsareadministered.

ProvidingessentialinformationGeneralprocedureforcollectingandprocessingspecimensforaerobicand/oranaerobicbacterialculture

Directassay

MorphologicalAssayElementAssayToxinAssay

MorphologicalAssayNon-stainedmicroscopicobservationDark-fieldmicroscopyObservingthemovementoflivebacteriaStainedmicroscopicobservationsGramstainAcid-faststainFluorescencestain

ElementAssayAntigendetectionNucleicaciddetectionToxindetectionAntigendetectionCoagglutinationtestPrecipitationtestELISAFluoroimmunoassay,FIARadioimmunoassay,RIACoagglutinationtestFluoroimmunoassay,FIANucleicaciddetectionNucleotidehybridizationPCRGenechipPCRGeneChip/microarrayToxindetectionEndotoxindetection--LimulustestExotoxindetection--ElekplatetestAnimaltest--LD50,ID50LimulustestElekplatetest

Culture&Identify

Isolation&CultureIdentifyMorphologicalidentifyBiochemicalreactionSerologicalassaysAntibioticssusceptibilitytestOthersIsolation&Culture:ColonySizeShapeColorSurfacefeaturesSmooth-RoughTransparencyHemolysis

BiochemicalReactions

SugarFermentationH2STestCitrateutilization

DiffusionMethodMIC&MBCMinimumInhibitoryConcentration,MICMinimumBactericidalConcentration,MBCBactericidaldrugsusuallyhaveanMBCequalorverysimilartotheMICBacteriostaticdrugsusuallyhaveanMBCsignificantlyhigherthantheMICEtestDiffusionmethod

+Dilutionmethod

SerologicalDiagnosis

Detectionantibodiesinthepatient’sserum

Acurrentinfectionshouldbe

IgMpositiveA4-foldorgreaterriseonantibodytiterbetweentheacuteserumsampleandtheconvalescentserumsample

AgglutinationtestComplementfixationtestNeutralizationtestELISAWesternblotanalysisSpeciesAsingleIgGantibodytiterisdifficulttointerpretbecauseitisunclearwhetheritrepresentsacurrentorapreviousinfectiontheconvalescentsampleisusuallytaken10-14daysaftertheacutesample.Bythistime,thepatienthasoftenrecoveredandthediagnosisesaretrospectiveoneMajordisadvantagePreventionandTreatmentofbacterialinfectionPreventionArtificialimmunityInnateimmunityActiveimmunityPassiveimmunity

Specific

PreventionActiveimmunityPassiveimmunityPreventionPassiveimmunityActiveimmunityVaccinesAdjuvantsCytokine,LAKcellAntiserum,AntitoxinsToxoidsImmunoglobulin

Vaccinesareantigenspreparedfrompathogensthatcanraiseaprotectiveimmuneresponse,yetdonotcauseillness.

ArtificialactiveimmunityVaccinesInactivatedvaccinesLive(attenuated)vaccinesSubunitvaccinesGeneengineeredvaccineDNAvaccinesToxoidInactivatedvaccine&Attenuatedvaccine較高,維持3~5年甚至更長較低,維持?jǐn)?shù)月~2年免疫效果不易保存,4℃數(shù)周易保存,約1年保存及有效期量較小,1次量較大,2~3次接種劑量與特點(diǎn)活減毒株死,強(qiáng)毒株制劑特點(diǎn)活疫苗死疫苗區(qū)別點(diǎn)Antitoxin:

e.g.Tetanusantitoxinanddiphtheriaantitoxin

AntiserumImmunoglobulinCytokine

Artificialpassiveimmunityinvolvesgivingbothavaccinetoprovidelong-termprotection(preventiveinfection)andimmuneglobulintoprovideimmediateprotection(therapeuticandpreventiveinfectiousdisease).Active-passiveimmunityArtificialactiveandpassiveimmunityTreatoremergencyprevebtionPreventionMainusageshort,2~3WLong,severalyears~severalmonthsDurationFastslow,2~4WTimeofresponseAntibody,cytokineAntigensubstancePassiveimmunityAvtiveimmunityitms國家免疫規(guī)劃疫苗:2008年2月

以前:乙肝疫苗、卡介苗、脊灰疫苗、百白破疫苗、麻疹疫苗08:甲肝疫苗、流腦疫苗、乙腦疫苗、麻風(fēng)腮疫苗重點(diǎn)人群和地區(qū):出血熱疫苗、炭疽疫苗、鉤體疫苗預(yù)防的傳染病15種:乙肝、結(jié)核、脊灰、百日咳、白喉、破傷風(fēng)、麻疹、甲肝、流腦、乙腦、風(fēng)疹、腮腺炎、出血熱、炭疽、鉤體

AntimicrobialchemotherapyChemotherapyasasciencebeganwithPaulEhrlichinthefirstdecadeofthe20thcentury.Ehrlich’sexperimentsledtothearsphenamines(胂凡納明)forsyphilis,thefirstplannedchemotherapy.金葡菌菌血癥的死亡率

RubinRJetal.EmergingInfectDis1999;5:9-17青霉素

時代耐青霉素

時代苯唑西林時代萬古霉素

時代抗生素

前時代%

近年來,世界抗生素市場的平均年增長率約為8%,世界抗感染藥物市場銷售額為400億美元,約占全球治療性藥物市場的10%。各類抗感染藥具體銷售情況是:抗生素占最大份額(約250億~260億美元);抗病毒藥居第二位(約55億~56億美元);第三位為抗真菌藥(40億~42億美元);其余則為疫苗和抗原生動物藥等抗感染藥小品種。

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