厌氧性细菌

anaerobicbacteria厌氧性细菌Clostridium厌氧芽孢梭菌属Nonspore-FormingAnaerobicBacteria无芽孢厌氧菌Clostridium厌氧芽孢梭菌属anaerobic,gram-positivebacillicapableofformingendosporesthatareusuallywiderthanthediameteroftherodsinwhichtheyareformed严格厌氧菌，革兰阳性形成芽孢，比菌体大peritrichousflagella，non-capsule（exceptC.perfringens）周鞭毛，无荚膜（除产气荚膜梭菌外）exotoxin外毒素致病Preventionandtreatment：toxoidandantitoxin防治：类毒素与抗毒素C．tetani破伤风梭菌tetanus破伤风Morphology&Identificationround,terminalsporesthatareusuallywiderthanthediameteroftherodsinwhichtheyareformed.Thesporelooksliketheappearanceofadrumstick芽孢正圆，位于菌体顶端，使细菌呈鼓槌状Bloodagar,β-hemolyticzones–血平板上，有β溶血抵抗力–芽孢抵抗力很强–在干燥的土壤和尘埃中可存活数年Pathogensis&Immunity致病条件：伤口需形成厌氧微环境–伤口窄而深（如刺伤），有泥土或异物污染–大面积创伤、烧伤，坏死组织多，局部组织缺血–有需氧菌或兼性厌氧菌混合感染的伤口无侵袭力，仅在局部繁殖，其致病作用完全有赖于病菌所产生的外毒素ToxinsandEnzymestetanolysin破伤风溶素–oxygen-labilehemolysin对氧敏感的溶血素tetanospasmin破伤风痉挛毒素–plasmid-encoded,heat-labileneurotoxin质粒编码热不稳定的神经毒素–Protein蛋白质–responsibleforcausingtheclinicalmanifestations临床症状oftetanustetanospasmin破伤风痉挛毒素structure结构–producedduringthestationaryphaseofgrowth：asinglepeptide稳定期产生：一条多肽–releasedwhenthecellislysed：cleavedintoalight(Achain)andaheavy(Bchain)subunit细菌裂解释出菌体：断裂为轻链（A链）-S-S-重链（B链）–Bchain：神经节苷脂结合的单位–Achain：azincendopeptidase锌内肽酶与神经系统的结合–B链识别运动神经元外胞浆膜上的受体并结合，促使毒素进入细胞内小泡中内在化作用–小泡从外周神经末稍沿神经轴突逆行向上，到达运动神经元细胞体，进入传入神经末稍，最终进入中枢神经系统膜的转位–通过重链N端的介导产生膜的转位使轻链进入胞质溶胶胞质溶胶中作用靶的改变–A链发挥毒性作用，使储存抑制性神经介质小泡膜蛋白发生改变，阻止抑制性神经介质γ-氨基丁酸的释放，使肌肉活动的兴奋与抑制失调，造成痉挛性麻痹ClinicalFindings–trismusorlockjaw牙关紧闭–sardonicsmile苦笑面容–persistentbackspasm痉挛(opisthotonos角弓反张）免疫性破伤风免疫属外毒素免疫，主要是抗毒素发挥中和作用（毒素与中枢神经组织结合非常牢固，一旦结合即非抗毒素所能中和）病后不会获得牢固免疫力获得有效免疫力的途径是人工免疫DiagnosticLaboratoryTestsThediagnosisrestsontheclinicalpictureandahistoryofinjury.一般不进行涂片镜检和分离培养典型的症状和病史即可作出诊断Prevention&Treatmentpropercareofwoundscontaminatedwithsoilactiveimmunization：toxoids类毒素Emergencyprevention：antitoxin抗毒素（tetanusantitoxin，TAT）Treatment：–verylargedosesofantitoxin–administrationofpenicillin防治原则防止创口厌氧微环境的形成特异性预防：注射破伤风类毒素三联疫苗免疫程序：3、4、5月3次2、7岁加强2次特殊情况1次紧急预防：注射破伤风抗毒素（tetanusantitoxin，TAT）特异性治疗：早期足量使用抗毒素及抗生素C．perfringens产气荚膜梭菌alarge,rectangular,gram-positivebacillus两端平切粗大杆菌Theovalsporeisplacedsubterminally椭圆形芽孢位于次极端capsulatedandnon-motile有明显的荚膜，不能运动culutre培养特性growsrapidly,metabolicallyactive生长迅速，代谢活跃adoublezoneofhemolysisonbloodagar血琼脂平板：双层溶血环内环完全溶血-θ毒素外环不完全溶血-α毒素Naglerreactiononeggyolkmedium蛋黄琼脂平板：Nagler反应Milkmedia：stormyfermentation牛奶培养基：“汹涌发酵”Classification分型fivetypes分为5个毒素型TypeAperfringenscausesmostofthehumaninfections.对人致病的：A型Pathogenesis&ImmunityToxinsandEnzymesAlphatoxinα毒素–lecithinase卵磷脂酶–Thistoxinisassociatedwithincreasedvascularpermeabilitywithmassivehemolysisandbleeding,tissuedestruction(asfoundinmyonecrosis),hepatictoxicity,andmyocardialdysfunction引起血管通透性增加伴大量溶血、组织坏死、肝脏、心功能受损Enterotoxin肠毒素Pathogenesis所致疾病gasgangrene气性坏疽–Atype–Conditionsaresimilartothoseinrelationtotetanus.致病条件与破伤风梭菌相同–spreadsin1-3days，rapidlyprogressingnecrosis,toxemiaanddeath.1－3天发病，快速进行性坏死，毒血症，死亡气性坏疽–主要由A型产气荚膜梭菌引起–致病条件与破伤风梭菌相同–潜伏期短，发展迅速，病情险恶，死亡率高组织坏死，气肿和全身中毒为特征组织坏死、血管内皮损伤，通透性上升出血、水肿、局部坏死分解糖产气，压迫软组织、血管加重组织坏死（捻发音）分解组织，病变迅速扩散，引起全身中毒症状foodpoisoning食物中毒–theingestionoflargenumbers(108to109organisms)ofclostridiathathavegrowninwarmedmeatdishes食入被大量细菌污染的食物（多为肉类）–diarrhea--usuallywithoutvomitingorfever--in6-18hours在6-18小时内引起无发热、无呕吐的腹泻坏死性肠炎–C型DiagnosticLaboratoryTestsThelaboratoryperformsonlyaconfirmatoryrole实验室检查仅有证实作用Themicroscopicdetection直接涂片镜检–gram-positivebacilliinclinicalspecimens,usuallyintheabsenceofleukocytes革兰阳性杆菌，白细胞少culture分离培养–adoublezoneofhemolysisonbloodagar–Naglerreactiononeggyolkmedium–Milkmedia：stormyfermentationfoodpoisoningisdocumentedbyrecoveryofmorethan105organismspergramoffoodor106bacteriapergramoffecescollectedwithin1dayoftheonsetofdisease如怀疑食物中毒，在发病后一日内，检出大于105病菌/克食品或106病菌/克粪便可确诊Prevention&Treatmentpromptandextensivesurgicaldebridement及时和扩大的清创Administrationofantimicrobialdrugs,penicillin服用抗生素Polyvalentantitoxin多价抗毒素Hyperbaricoxygen高压氧C．botulinum肉毒梭菌Spore：ovalandsubterminal芽孢呈椭圆形，粗于菌体，位于次极端Sporewithstandboilinginwaterforseveralhours,usuallydestroyedbymoistheatat120℃within5min.芽孢抵抗100℃几小时，湿热120℃5分钟破坏。fourgroups(ItoIV)分四个群(ItoIV)Eightserotype：A,B,C1,C2,D,E,F,GPathogensis&ImmunityToxin–Cbotulinumtoxins肉毒毒素areamongthemosthighlytoxicsubstancesknown.Thelethaldoseforahumanisprobablyabout0.1μg.剧毒，对人致死量为0.1µgdestroyedbyheatingfor1minutesat100℃.100℃1分钟破坏Similartotetanustoxin与破伤风外毒素相似Mechanism作用机制肉毒毒素经胃肠道吸收入血后，作用于中枢神经系统的脑神经核和外周神经一肌肉神经接头处以及自主神经末梢，阻碍乙酰胆碱的释放，引起运动神经末梢功能失调，导致肌肉弛缓性麻痹。毒素经内化作用进入细胞内由细胞膜形成的小泡中，不像破伤风毒素从外周神经末梢沿神经轴突上行，而是留在神经肌肉接头处。ClinicalFindings所致疾病FoodborneBotulism肉毒食物中毒–进食污染食物（多为罐头、肉制品、豆制品）发生食物中毒---食入毒素–临床表现：少见胃肠道症状，主要为神经末梢麻痹（flaccidparalysis弛缓性麻痹）乏力、头痛→眼肌麻痹：复视、斜视、眼睑下垂→咽部肌肉麻痹：吞咽、咀嚼困难、口齿不清→膈肌麻痹，呼吸困难→窒息死亡神志清楚病死率高InfantBotulism婴儿肉毒病–细菌进入肠道，繁殖，产生毒素而致病–以6个月以内的小婴儿居多–症状与肉毒食物中毒类似，便闭、吸乳、啼哭无力–病死率不高Woundbotulism创伤感染肉毒病DiagnosticLaboratoryTests微生物学检查法specimen标本–toxin毒素–foodbornedisease：leftoverfood食物中毒患者：食物–infantbotulism：bowelcontents(feces)婴儿肉毒病患者：粪便–heatingthespecimenfor10minut