章、細(xì)菌感染檢查與防治

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(zhǎng)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(guó)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(shí)代耐青霉素

時(shí)代苯唑西林時(shí)代萬(wàn)古霉素

時(shí)代抗生素

前時(shí)代%

近年來(lái)，世界抗生素市場(chǎng)的平均年增長(zhǎng)率約為8%，世界抗感染藥物市場(chǎng)銷(xiāo)售額為400億美元，約占全球治療性藥物市場(chǎng)的10%。各類(lèi)抗感染藥具體銷(xiāo)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(dòng)物藥等抗感染藥小品種。