消毒劑的選擇與確認(rèn)微生物的抗性不同微生物對消毒劑的抗性也各不相同。它們的順序從大到小的排列如下:Typeofmicroorganisms微生物種類examples實(shí)例Bacterialspores細(xì)菌芽胞BacillussubtilisandClostridiumsporogenes枯草桿菌，產(chǎn)抱梭菌Mycobacteria分枝桿菌Mycobacteriumtuberculosis結(jié)核分枝桿菌Nonlipid-coatedviruses親脂病毒Poliovirusandrhinovirus脊髓灰質(zhì)病毒，鼻病毒Fungalsporesandvegetativemoldsandyeast真菌胞子，生長態(tài)的霉菌與酵母菌Trichophyton,cryptococcus,andCandidaspp發(fā)群菌，隱球菌屬，念珠菌屬等Vegetativebacteria生長態(tài)的細(xì)菌Pseudomonasaeruginosa,StaphylococcusAureus,andsalmonellaspp綠膿桿菌，金色葡萄球菌，和沙門氏菌等等Lipid-coatedviruses親水病毒herpessimplexvirus,hepatitisBvirus,andhumanimmunodeficiencyvirus單純性皰疹病毒，乙肝病毒，人體免疫缺陷病毒消毒劑的分類化學(xué)消毒劑按他們的化學(xué)型分類。其中包括醛，醇，鹵素，過氧化物，季胺類化合物，和酚類化合物。Chemicalentity化學(xué)體Classification分類Example例證Aldehydes醛sporicidalagent殺胞子劑2%glutaldehydeAlcohols醇Generalpurposedisinfectant,antiseptic,Antiviralagent,一般用途的消毒劑，抗菌劑和抗病毒試劑70%isopropylalcoho1,70%alcohol,70%的異丙醇，70%的乙醇ChlorineandSodiumHypochlorite氯和次氯酸鈉sporicidalagent殺抱子劑0.5%sodiumhypochiorite0.5%次氯酸鈉Phenolics酚類化合物generalpurposeDisinfectant一般用途的消毒劑50pgpergchlorocresol,500pgpergchloroxylenol50pg/g氯甲酚,500pg/g對氯間二甲酚Ozone臭氧sporicidalagent殺胞子劑8%gasbyweight8%的氣體（重量百分比）HydrogenPeroxide過氧化氫vaporphasesterilant,liquidSporicidalAgent,antiseptic蒸汽的殺菌劑，液體殺胞子劑,抗菌劑4pgpergH2O2vapor,10%-25%solution,3%solution4pg/g雙氧水蒸汽，10%—25%溶液，3%溶液Substituteddiguanides取代的二甲雙antisepticagent抗菌劑0.5%chlorhexidinegluconate0.5%葡萄糖酸洗必太Peraceticacid過氧乙酸liquidsterilant,VaporphaseSterilant液體殺菌劑，蒸汽的殺菌劑0.2%peraceticacid,1pgpergperaceticacid0.2%peracetic酸，1pg/g過氧乙酸Ethyleneoxide環(huán)氧乙烷vapor-phaseSterilant蒸汽的殺菌劑600pgpergethyleneoxide600pg/g環(huán)氧乙烷QuaternaryAmmoniumCompounds季氨鹽化合物generalpurposedisinfectant,antiseptic一般用途的消毒殺菌劑，抗菌劑200pgpergbenzalkoniumchloride200pg/g潔爾滅氯化物p—propiolactone0—丙而酯sporicidalagent殺抱子齊！J100pgpergp-propiolactoneB一丙內(nèi)酯抗微生物化學(xué)試劑可分為三類：殺菌劑，消毒劑和殺胞子劑。這里列出的是通常與每個類別相關(guān)聯(lián)的試劑類型。殺菌劑由于蒸發(fā)快、殘留低的特點(diǎn)，消毒已被帶入APA的物品時應(yīng)使用醇類（即異丙醇和乙醇）化學(xué)試劑。除非與材料存在相容性問題，應(yīng)使用70%異丙醇（IPA）代替70%乙醇（EtOH）,因?yàn)楫惐嫉臍⒕饔帽徽J(rèn)為比乙醇稍大。雖然醇類對

活細(xì)胞具有相對較好的殺菌活性，但醇類的快速揮發(fā)顯著降低了其效力。醇類殺菌劑對抱子無效。消毒劑酚類和季鏤化合物對活細(xì)胞具有廣譜殺菌活性。這些化學(xué)物質(zhì)典型特征會帶來表面殘留。緊隨它們的使用應(yīng)清除該部分殘留，例如通過異丙醇擦拭清除。殺狗子劑次氯酸鈉（漂白劑）和過氧化氫/過氧乙酸化合物是廣泛使用的殺泡子劑。過氧化氫也可用于（通常在6%濃度）提供對霉菌和一些抱子形式微生物提供抗菌活性。過氧化物比醇類抗菌活性更高，分解后形成水和氧氣，不產(chǎn)生留殘。當(dāng)消毒程序要求清除胞子類微生物時應(yīng)采用化學(xué)殺抱子劑。不幸的是，除過氧化氫外這些化學(xué)品均有一定殘留。消毒劑的作用機(jī)理以下列出了一些具有代表性的消毒劑的活性的作用位置和作用方式TargetDisinfectant目標(biāo)消毒劑Cellwall細(xì)胞壁Cellwall細(xì)胞壁Cellwall細(xì)胞壁Cellwall細(xì)胞壁Formaldehyde,hypochlorite,andmercurialsCellwall細(xì)胞壁Cytoplasmicmembrane,actiononAnilidesandhexachlorophene苯氨，六氯酚Hexachlorophene六氯酚membranepotential苯氨，六氯酚Hexachlorophene六氯酚Membraneenzymes,actiononelectrontransportchain糖皮質(zhì)激素酶，電子轉(zhuǎn)移作用ActiononATP

三磷酸腺昔作用ChlorhexidineandethyleneoxideActiononATP

三磷酸腺昔作用Actiononenzymeswith-SHgrouEthyleneoxide,glutaraldehyde,hyPS筑基酶作用PS筑基酶作用環(huán)氧乙烷，戊二醛，過氧化氫，次氯酸鹽，碘，汞制劑ActionongeneralmembranepermAlcohols,chlorhexidine,andquatereability一般膜滲透性作用naryammoniumcompoundseability一般膜滲透性作用Cellcontents,generalcoagulationChlorhexidine,aldehydes,hexachlo細(xì)胞內(nèi)含物，一般凝固細(xì)胞內(nèi)含物，一般凝固細(xì)胞內(nèi)含物，一般凝固細(xì)胞內(nèi)含物，一般凝固細(xì)胞內(nèi)含物，一般凝固rophene,andquaternaryammoniumcompounds氯己定，醛，六氯酚，季胺類化合物Ribosomes細(xì)胞內(nèi)含物，一般凝固Ribosomes核糖體Ribosomes核糖體Nucleicacids核酸Hypochlorites次氯酸鹽Thiolgroups筑基Ethyleneoxide,glutaraldehyde,hydrogenperoxide,hypochlorite,mercurials環(huán)氧乙烷，戊二醛，過氧化氫，次氯酸鹽，汞制劑Aminogroups氨基Ethyleneoxide,glutaraldehyde,andhypochlorite環(huán)氧乙烷，戊二醛，次氯酸鹽Generaloxidation一般氧化Ethyleneoxide,glutaraldehyde,andhypochloriteRibosomes核糖體Nucleicacids核酸Hypochlorites次氯酸鹽Thiolgroups筑基Ethyleneoxide,glutaraldehyde,hydrogenperoxide,hypochlorite,mercurials環(huán)氧乙烷，戊二醛，過氧化氫，次氯酸鹽，汞制劑Aminogroups氨基Ethyleneoxide,glutaraldehyde,andhypochlorite環(huán)氧乙烷，戊二醛，次氯酸鹽Generaloxidation一般氧化Ethyleneoxide,glutaraldehyde,andhypochlorite環(huán)氧乙烷，戊二醛，次氯酸鹽用于消毒程序的新的供應(yīng)商和新的殺菌化學(xué)試劑應(yīng)在使用前根據(jù)建立的程序進(jìn)行確認(rèn)。令人滿意的審計(jì)、確認(rèn)測試和清楚定義的檢驗(yàn)報(bào)告（C0A）被認(rèn)為是確認(rèn)中的重要部分。如果試劑的配方、包裝或生產(chǎn)場所有所變更，則應(yīng)進(jìn)行評估以確定是否需要重新確認(rèn)。Whenchoosinganewantimicrobialchemicalagentfromasupplier,evaluatethesupplier's:在從一個供應(yīng)商處選擇一個新的殺菌化學(xué)試劑時，要評估供應(yīng)商的:?Productliterature/technicaldata產(chǎn)品文字/技術(shù)數(shù)據(jù)Materialsafetyinformation物料安全信息Materialcompatibility物料相容性Compatibilityinformation相容性信息Storageconditions存貯條件Packagingpresentations包裝Expiringdating有效期Disposalrequirements處理要求Efficacydata有效性數(shù)據(jù)Sterilityandsterilizationinformation(iftheproductisprovidedsterile)無菌和滅菌信息(如果產(chǎn)品是作為無菌產(chǎn)品)Inevaluatingsupplierinformationrelatedtotheefficacyofanantimicrobialchemicalagent,itisimportanttounderstandthetestingmethodologyandstandardsused.Theseoftenvarydependingonwheretheagentwasregisteredandtheclaimsmaderegardingitsuse.在評估關(guān)于殺菌化學(xué)試劑有效性的供應(yīng)商信息時，了解所用的測試方法和標(biāo)準(zhǔn)非常重要。這些通常根據(jù)試劑注冊地不同，以及關(guān)于其用途的聲明而有差異。Dependingonthespecificuseoftheantimicrobialchemicalagentandexperiencewiththespecificsupplier,anauditmayneedtobeperformed.Extraattentionshouldbegiventothefollowingduringanaudit:根據(jù)殺菌化學(xué)試劑的特定用途和特定供應(yīng)商的經(jīng)驗(yàn)，可能需要進(jìn)行審計(jì)。在審計(jì)中需要注意以下方面：Environmentalcontrolandcleaningofthemanufacturingorpackagingareaandequipmentusedtomanufacturetheantimicrobialchemicalagent.用于生產(chǎn)殺菌化學(xué)試劑的生產(chǎn)或包裝區(qū)域和設(shè)備的環(huán)境控制和清潔Controlanddisinfectionorsterilizationoftheantimicrobialchemicalagentpackagingcontainers.殺菌化學(xué)試劑包裝容器的控制和消毒或滅菌Documentationandreviewofantimicrobialchemicalagentproductionprocessingactivities.殺菌化學(xué)試劑生產(chǎn)處理活動的文件記錄和審核Forasepticallyfilledagents,theenvironmentalmonitoring(EM)programdata,includingalertandactionlevels,trending,correctiveactionstaken,andtheuseofneutralizingagentsfortheEMmediaused.對于無菌灌裝試劑，環(huán)境監(jiān)測（EM）程序數(shù)據(jù)，包括警戒限和行動限、趨勢、所采取的糾正措施以及所用EM培養(yǎng)基的中和劑使用Foragentslabeledassterile,sterilitytestingdataandqualificationofthesterilizationprocess.對于標(biāo)識為無菌的試劑，無菌測試數(shù)據(jù)和無菌工藝確認(rèn)Watersystemsandthequalityofwaterusedinthemanufacturingprocess.水系統(tǒng)和工藝用水的質(zhì)量Packageorcontainerintegritystudies.包裝或容器完整性研究Fordouble-andtriple-baggedcontainers,disinfectionoffilledcontainerandoverwrappingintegrity.對于雙層或三層袋裝容器，灌裝容器消毒和外包裝完整性Fordouble-andtriple-baggedcontainerswhereaclaimofsterilityismadeforinnerbags,qualificationofthesterilizationprocessused.對于雙層和三層袋裝容器，如果內(nèi)袋有無菌聲明，所用的滅菌過程的確認(rèn)Handlingandstorageoffinishedproductcontainersorworkinprogress.成品容器或中間產(chǎn)品的處理和存貯Studyresultstosupportlabelclaimofagent.支持試劑標(biāo)簽聲明的研究結(jié)果Documentationrelatedtoregulatoryapprovalofagent.與試劑法規(guī)批準(zhǔn)有關(guān)的文件記錄Changecontrol:customernotificationofingredientchangesorprocesschangesthatwouldaffectthefinishedproduct一forexample,wrapping,irradiation,andsterilization.變更控制：會影響成品，例如，包裝、輻射和滅菌，的成分變更或工藝變更時對客戶的通知消毒劑的確認(rèn)Qualificationtestingofanewantimicrobialchemicalagentshouldincludebothlaboratoryandinsitutesting.Chemicalanalysisoftheactivesandmicrobialefficacytestingshouldbeperformed.對一個新的抗菌化學(xué)試劑的確認(rèn)測試應(yīng)包括化驗(yàn)室和現(xiàn)場測試。要進(jìn)行活性化學(xué)分析以及微生物有效性測試。Chemicalanalysisoftheactivesmaybeprovidedbythevendoror,alternatively,performedin-houseorbyaqualifiedcontractlaboratoryusingthevendor，smethod.Microbialefficacytesting,whetherinsuspensionorincarrierstudies,shouldbeperformedin-houseorbyaqualifiedcontracttestinglaboratory.活性化學(xué)分析可以由供應(yīng)商提供，或者內(nèi)部測試，或由一個經(jīng)過確認(rèn)的合同化驗(yàn)室使用供應(yīng)商的方法進(jìn)行測試。微生物有效性試驗(yàn)，如果是在混懸液中或在載體研究中，應(yīng)內(nèi)部進(jìn)行測試，或由經(jīng)過確認(rèn)的第三方化驗(yàn)室進(jìn)行測試。Theantimicrobialschemicalagentsusedfortestingshouldbeclosetoorbeyondtheirstatedin-useexpirationdate(thisshouldtakeintoaccountareadytouseand/orausedilutionpreparedfromaconcentrateexpiry).Testingshouldbedoneinreplicateonmultiplelotsoftheantimicrobialchemicalagentwhereapplicable.Itshouldbenotedthatsignificantregistrationtestingonmultiplelotsoftheagentisperformedbythecompanyregisteringtheproducttoensureproductconsistencybetweenlotsandstabilitythroughoutthestatedshelflife.用于測試的抗菌化學(xué)試劑應(yīng)鄰近或超出其使用有效期(這里要考慮直接使用和/或稀釋使用時濃縮液的有效期)。如果可以的話，應(yīng)對多個批次進(jìn)行平行測試。要注意的是對多批試劑的重要的注冊測試是由注冊公司來進(jìn)行的，以確保產(chǎn)品不同批次之間的一致性，以及其所聲明的整個貨架期的穩(wěn)定性。Additionalqualificationmaybeperformedifchangesinproductformulationorpackagingorsiteinvestigationsdeemitnecessary.Informationsupportingthequalificationincludesthefollowingsevenareas:如果生產(chǎn)配方或包裝進(jìn)行了變更，或現(xiàn)場調(diào)查認(rèn)為必要時，可能需要進(jìn)行再次確認(rèn)。支持確認(rèn)的信息包括以下七個方面：Descriptionofpackaging,label,andcontainertype包裝、標(biāo)簽和容器類型描述Descriptionofingredientsandconcentrations成分和濃度描述Lotorbatchnumber批號Efficacytestingresults有效性測試結(jié)果Irradiationorothersterilizationverificationcertification輻射或其它滅菌確認(rèn)認(rèn)證Safetydatasheetinformation安全數(shù)據(jù)信息表Disposalinformation處理信息EfficacyTesting有效性測試Thedemonstrationofantimicrobialchemicalagentstoprovidetheirrespectivekillsisafunctionoftheconcentrationofmicroorganismspresent,thetypeofmicroorganisms,thechoiceofagent,theconcentrationoftheagent,theporosityortextureofthesurfacetobecleaned,themethodofapplication,andthecontacttime.Routinely,theagentusedshouldbeeffectiveagainstthenormalmicrobialvegetativeflorarecoveredfromthefacility.Manyefficacytestingguidelines,suchastheAssociationofOfficialAnalyticalChemist(AOAC),suggesthighmicroorganisminoculumlevelsrequiringlongercontacttimestodestroythepopulationofcells.Asthenormalcleanroombioburdenlevelisverylow,theinoculumlevelsfortestingwouldideallydepictlevelsseeninthecontrolledarea.Asthiswouldnotbepracticalinatestenvironmentahigherinoculumlevelshouldbeusedandshouldnotexceed105.Theantimicrobialchemicalagentusedwithintheindustrycanbebrokenintothreegeneralareas:sanitizers,disinfectants,andsporicides.抗菌化學(xué)試劑殺滅效果是被殺滅微生物濃度、微生物類型、試劑選擇、試劑濃度、要清潔的表面的孔隙度或質(zhì)地、所使用的方法以及接觸時長的函數(shù)。一般來說,所用的試劑應(yīng)對從設(shè)施中回收到的常規(guī)微生物植物群落有效。許多有效性測試指南，例如美國分析化學(xué)家協(xié)會(A0AC),建議高濃度微生物接種需要更長的接觸時長以摧毀細(xì)胞群。由于常規(guī)潔凈間生物負(fù)載水平非常之低，測試的接種水平理想地描述了受控區(qū)域所見水平。由于這種情況在測試環(huán)境中不現(xiàn)實(shí)，需要使用更高的接種水平，應(yīng)超出105。行業(yè)內(nèi)所用的抗菌化學(xué)試劑可以分為三個常規(guī)區(qū)域：滅菌劑、消毒劑和殺胞子劑。Sanitizers滅菌劑Sanitizersprovideminimalreductioninthirtysecondstotenminutesandareoftenusedforlowlevelsofvegetativemicroorganisms.Thetypeofsanitizerwilldictatetheappropriatecontacttimerequired.Alcoholisanexampleofacommonlyusedsanitizer.殺菌劑提供在30秒到10分鐘最小減少量，通常用于低水平的植物性微生物。滅菌劑的類型決定了所需適當(dāng)?shù)慕佑|時長。乙醇是常用的滅菌劑的例子。Disinfectants消毒劑Disinfectantsexhibitahigherlevelofefficacythansanitizers,andtheirkillisdependentontheinoculumsandthecontacttime.Disinfectantswilltypicallykillvegetativemicroorganismswiththeexceptionofspore-formingmicroorganisms.Examplesincludequaternaryammoniumcompoundsandphenolics.消毒劑比滅菌劑具有更高的有效性，其殺滅性與接種水平和接觸時長無關(guān)。消毒劑一般會殺滅植物性微生物，抱子形態(tài)除外。消毒劑例子包括季胺鹽和酚醛物。Sporicides殺他子劑Sporicidesprovideuptoatotalkilldependingontheinoculumsandthewetcontacttimeandwillkillbacteri