《抗生素简介》PPT课件

抗生素簡介,“Thefutureisnotwhatitusedtobe”-YogiBerra,細菌抗藥性產生,有效治療病人,抗生素,抗生素Antibiotics：是指一些由黴菌所產生的物質，能抑制細菌的生長。人類利用這種物質稍加改變，而用來對抗細菌對人類的侵襲。Antimicrobialagents:能抑制生長或殺死對人類能造成疾病的微生物（寄生蟲、黴菌、細菌、立克次體、病毒）的製劑（天然或合成）,ChineseEmperorShenNung(神農氏)wroteatreatiseontheuseofchangshan(常山）infever.,2735BC,Historyofinfectiousdiseases,抗生素的歷史,約2500年前中國用黃豆發霉發酵後製成膏藥用於治療疔瘡等感染Early1900s:arsenicandbismuthforsyphilis1929Fleming(佛來明)：實驗室受黴菌(Penicillium)污染而發現。1940年代：純化後製成第一種用於人類之抗生素-青黴素(Penicillin),細菌的分類,革蘭性陽性菌葡萄球菌Staphylococcus：MSSA,MRSA(methacillinresistantS.aureus)鏈球菌SreptococcusGroupA,B,C,G.腸球菌Enterococcus革蘭性陰性菌腸菌屬：E.coli,Klebsiellapneumoniae綠膿桿菌Pseudomonasaeruginosa;Acinetobacter厭氧菌Bacteroidesfragilis,如何選擇抗生素,病人年齡、原本疾病。疾病：感染部位細菌抗生素效果副作用價格,發燒、休克意識不清,感染？,不需使用抗生素,細菌、病毒黴菌或其他,感染部位？泌尿道、呼吸道,取得適當檢體做培養Urine,Blood,Sputum.,有抗微生物藥劑可有效治療？,選擇適當抗微生物藥劑,否,是,是,否,臨床上抗生素用在下列三方面,1.EmpiricalTherapy(經驗式療法)：治療由經驗推想的病原菌造成的感染。2.Well-knowninfection：治療已知致病病源體的感染症。3.Prophylaxis：預防可能發生的感染症。,抗生素使用原則,1.由各項臨床資料來判斷病人是否需要使用抗生素。2.若決定使用抗生素，是否已採取適當的、足夠的檢體送檢。3.此次感染最有可能的致病菌是什麼？4.對可能或已確定的病菌，最佳的藥物是什麼？5.是否需要合併使用兩種以上的抗生素？6.病人本身有無須特別考量的問題？7.經由何種途徑給藥是最佳的給藥方式？8.應該給予多少劑量？9.細菌培養得到結果後，初始之抗生素是否要做調整？10.應該要給予多久？,1.由各項臨床資料來判斷病人是否需要使用抗生素。,有明顯的細菌感染症狀蜂窩組織炎、傷口感染肺炎：膿痰、高燒、X光片泌尿道感染：頻尿、腰酸、高燒、濁尿由臨床資料判斷可能有細菌感染明顯的畏寒、發燒、白血球增多病情危急時疑似有敗血症白血球缺乏而有發燒時疑有腦膜炎或急性心內膜炎,2.若決定使用抗生素，是否已採取適當的、足夠的檢體送檢。,細菌培養血液、痰液、尿液嗜氧、厭養菌結核菌、黴菌抹片染色GramstainAcidFaststainIndianinkstain,3.此次感染最有可能的致病菌是什麼？,感染部位UTI:E.coliPneumonia:StreptpcoccuspneumoniaeCellulitis:S.aureus,GroupAsreptococcus格蘭氏染色(Gram+/-)病人之年齡、原本疾病流行病學資料,4.對可能或已確定的病菌，最佳的藥物是什麼？,該致病菌的首選藥物S.aureus:oxacillin,cephalosporinMRSA:Vancomycin,TeicoplaninS.pyogenes,S.pneumoniae:penicillinGK.pneumoniae,E.coli:CephalosporinPseudomonasaeruginosa:anti-pseudomonaspenicillinorcephalosporinLegionellapneumophila:erythromycinMycoplasmapenuomia:eythromycin,4.對可能或已確定的病菌，最佳的藥物是什麼-2？,是否有對抗生素過敏的病史抗生素對組織的穿透性CSF:BBB的穿透性膽道感染：肝臟排泄泌尿道感染：腎臟排泄藥物可能的副作用孕婦、兒童殺菌性(bactericidal)或抑菌性藥物(Bacteriostatic)廣效性(broad-spectrum)或窄效性藥物(narrow-spectrum)藥物的費用,5.是否需要合併使用兩種以上的抗生素？,需合併兩種以上抗生素的情況有敗血症或白血球過低的病人多種細菌感染需對致病菌有更強的殺菌力時為了避免抗藥細菌產生常用之合併用法Penicillin+gentamicin:streptococci,enterococciPiprilorFortum+aminoglycoside:Pseudomonasaeruginosa-lactamaseinhibior+-lactam:drugresistantbacteria,6.病人本身有無須特別考量的問題？,腎功能情形肝功能情形病人的年齡老年人、嬰幼兒藥物過敏史先天遺傳上的問題G-6-P-D,7.經由何種途徑給藥是最佳的給藥方式？,靜脈注射肌肉注射有出血傾向或休克狀態（因肌肉循環不佳、藥物吸收不良）避免使用口服投予,8.應該給予多少劑量？,病人年齡老年人、嬰幼兒體重腎功能肝功能PK/PD,9.細菌培養得到結果後，初始之抗生素是否要做調整？,根據培養盡可能改用較窄效、傳統、無副作用、價錢便宜的藥物。病人在療程中的變化：是否退燒病情時否已獲得改善是否需要考慮其他致病菌膿瘍是否已經引流,如何評估抗生素的使用效果,臨床：發燒減退生理狀況改善：-血壓穩定、呼吸速率改善、意識狀況進步、痰量減少。全身狀況改善：-胃口進步、疼痛減少、活動力增加。實驗室診斷：WBCcount(血液、CSF、Ascites、Pleuraleffusionetc.)放射線等檢查(CxR,CT,MRI,abdominalecho,Bonescangalliumscanetc.)CRP,ESR,抗生素治療未達預期效果原因,1.診斷錯誤2.抗生素的劑量或給藥間隔有誤3.藥物吸收不足或代謝增加4.膿瘍未引流或異物未移除5.感染部位的抗生素濃度不夠6.併用抗生素有拮抗作用7.出現具抗藥性或耐受性的菌株8.另有不同的細菌造成繼發性感染,10.應該要給予多久？,Meningitis:7-14daysPneumonia:10-14daysLung/liverabscess:4-6weeksEmpyema:4-6weeksInfectiveendocarditsi:4-6weeksPyelonephritis:14-21dysCystitis:3-7days,抗生素分類,Beta-LactamPenicillinsCephalosporinsandCephamycinsCarbapenemBeta-lactamaseinhibitorsAminoglycosidesgentamicin,netilmicin,tobramycin,amikacinQuinolone,OthersTetracyclineGlycopeptideMacrolide,ClindamycinSulfonamideandTrimethoprimMetronidazoleRifampicinAnti-TB,fungal,virusagent,-lactamantibiotics,Penicillins,Cephalosporins,Monobactams,Carpapenems,ClassificationofPenicillins,NaturalpenicillinsPenicillinG,PenicillinGbenzathine,penicillinVAminopenicillinsAmpicillin,AmoxicillinPenicillinase-resistantpenicillinsMethicillin,Oxacillin,cloxacillin,dicloxacillinCarboxypenicillinsPiperacillinPenicillinsCombinedwithBeta-lactamaseinhibitorAugmentin,Unasyn,Timentin,Tazocin,Naturalpenicillin,有效範圍對革蘭氏陽性菌中的Streptococcus及Enterococcus有效；但台灣地區的Streptococcuspneumoniae50-70%具抗藥性。Treponemapallidum（梅毒）有效。對厭氧菌中的革蘭氏陽性菌如Peptococcus,Peptpstreptococcus,Clostridiumtetani（破傷風）,C.perfringens等有效。MSSA,MRSA均無效。Penicillin(3MU/vial),BenzathinePenicillin(Retarpen2.4MU),Aminopenicillins,有效範圍：對革蘭氏陽性菌中的Streptococcus及Enterococcus有效；但對MRSA,MSSA無效。對簡單的革蘭氏陰性菌如E.coli,Proteus有效，但台灣地區的抗藥性超過50%。對其他革蘭氏陰性菌及厭氧菌無效。Amoxicillin(Hiconcil250,500mg,25mg/ml);Ampicillin(Servicillin,Pentrexyl),Extended-spectrumpenicillins,有效範圍：此類藥物對更多的革蘭氏陰性細菌有效，包括簡單的E.coli,Klebsiella,Proteus，以及部分較困難的陰性腸內菌，對Pseudomonasaeruginosa亦有效。對Streptococcus及Enterococcus亦可有效。但對MRSA及MSSA則仍無效。Sulbenicillin(Lilacillin),Piperacillin(Pipril),Penicillinase-ResistantPenicillin,有效範圍：對MSSA最為有效，對Streptococcus也有效，但較NaturalPenicillin差。對MRSA,Enterococcus,即Gramnegative無效。Dicloxacillin(Diclocin),Oxacillin(Prostaphlin):500mg/vial,1-2gq4-6h,Beta-lactamaseinhibitor,-lactamaseinhibitor:clavulanicacid,sulbactam,tazobactam.上市之商品有：Unasyn:Ampicillin+SulbactamAugmentin:Amoxicillin+ClavulanicacidTimentin:Ticarcillin+ClavulanicacidTazocin:Piperacillin+Tazobactam細菌因製造-lactamase而具抗藥性時，可藉此恢復抗菌力對厭氧菌效果更加強。,Chemicalstructuresofampicillin,sulbactamandsultamicillin1,2,S,N,O,O,O,O,CH2,O,C,CH3,S,O,N,CONH,H,NH2,C,O,Sultamicillin,N,S,NH2,CHCONH,H,CH3,CH3,COOH,O,Ampicillin,N,S,O,O,CH3,CH3,COOH,O,Sulbactam,Esterase,1.Campoli-RichardsDM,BrogdenRN.Drugs1987;33:577609.2.FriedelHAetal.Drugs1989;37:491522.,CH3,C,O,CH3,CH3,H,Mechanismofactionof-lactamaseinhibitors,WilliamsJD.IntJAntimicrobAgents1999;12(Suppl1):S3S7.,Inhibitorinactivates-lactamase,-Lactamcanreachpenicillin-bindingprotein(PBP),-Lactamalonemaybedegradedby-lactamase,PBP,PBP,PBP,Withinhibitor,Withoutinhibitor,-Lactam,-Lactamaseinhibitor,-Lactamase,InvitroactivityversuskeyGram-positiveorganisms,Susceptibility(%isolates)aAmpicillinA/SStaphylococcusaureus,OR(n=110)1NR58.2Staphylococcusepidermidis,OR(n=80)1NR98.8Streptococcuspneumoniae,Pen-S(n=53)20.03b0.03bStreptococcuspyogenes(n=294)30.25b0.25bA/S,ampicillin/sulbactam;OR,oxacillin-resistantisolates;NR,notreported;Pen-S,penicillin-susceptibleisolates.aUsingNCCLSbreakpoints.bNoNCCLSbreakpointsavailable;datapresentedasMIC90(g/ml).,1.MarshallSAetal.DiagnMicrobiolInfectDis1995;21:15368.2.JohnsonDMetal.DiagnMicrobiolInfectDis1996;25:13741.3.CullmanW.JChemother1995;7:215.,InvitroactivityversuskeyGram-negativeorganisms,Susceptibility(%isolates)aAmpicillinA/SHaemophilusinfluenzae,-lac+(n=35)10.084.0Moraxellacatarrhalis(n=111)116b0.25bKlebsiellapneumoniae(n=319)27.289.3Klebsiellaoxytoca(n=75)20.088.0Proteusmirabilis(n=196)293.499.5Escherichiacoli(n=1354)262.379.0Acinetobacterspp.(n=70)217.195.7Pseudomonasaeruginosa(n=569)21.85.3A/S,ampicillin/sulbactam;-lac+,-lactamase-producingisolates.aUsingNCCLSbreakpoints.bNoNCCLSbreakpointsavailable;datapresentedasMIC90(g/ml).,1.SmayevskyJetal.DiagnMicrobiolInfectDis2000;37:2614.2.MarshallSAetal.DiagnMicrobiolInfectDis1995;21:15368.,Invitroactivityversuskeyanaerobicorganisms,MIC90(g/ml)SpeciesAmpicillinA/SaBacteroidesfragilis10025648OtherBacteroidesfragilisgroupspecies25616Bacteriodesthetaiotamicron253.1Bacteroidesvulgatus256.3Clostridiumdifficile44Fusobacteriumspp.322Peptostreptococcusspp.81A/S,ampicillin/sulbactamaMIC90basedonampicillinconcentration,EdnieLMetal.AntimicrobAgentsChemother1998;42:5962.,Summary,Broad-spectrumantimicrobialactivityGram-positiveaerobesStaphylococcusaureus,Staphylococcusepidermidis,Streptococcuspneumoniae,StreptococcuspyogenesGram-negativeaerobesHaemophilusinfluenzae,Moraxellacatarrhalis,Enterobacteriaceae(Klebsiellapneumoniae,Enterobacterspp.,Proteusspp.,Escherichiacoli)AnaerobesBacteroidesfragilis,Bacteroidesspp.,Clostridium,FusobacteriumandPeptostreptococcusspp.,Piperacillin-tazobactam(Tazocin)抗菌範圍,Gram(+):大部分有效但下列無效MRSA,MRSEPenicillinresistantstreptococcusAmpicillinresistantenterococcusGram(-):Enerobacteriae:E.coli,P.mirabilis,K.pneumoniaeH.influenzae,B.catarrhalisPseudomonaeaeruginosa多重抗藥性G(-)bacilliAnaerobes,Dosage,Amoxicillin-Clavulanicaicd:Augmentin600mg/vial,1(875/125)g/tab,457(400/57)mg/5mlIV:1.2gq6hrs,PO:1#q12hrs,40-45mg/kg/dayAmpicillin-Sulbactam:Unasyn1.5gm/vial1.5-3gmq6hrsPiperacillin-Tazobactam:Tazocin2.25gm/vial2.25-4.5q4-6hrs,AllergicreactionstoPenicillins,Immediatereaction(2-30min)ErythemaorpruritusUrticariaAngioenemaWheezing,rhinitisHypotensionorshockAcceleratedractions(1-72hr)EyhthemaorpruritusUrticariaAngioedemaLaryngelaendemaWheezing,rhinitis,Latereaction(72hrs)MorbilliformeruptionsUritcaria-agioedemaUrticaria-arthralgiaSerumsicknessLesscommonreactionImmunehemolyticanemiaPulmonaryinfiltrationwitheosinophiliaInterstitialnephritisGranulocytopeniaThrombocytopeniaDrugfeverHypersensitivityvasculitisErythemamultiformDrug-inducedsystemiclupuserythematosus,Cephalosporin(Cephem)頭芽孢菌素,此類藥物的正確名稱為cephem類依結構再分為cephalosporin(對厭氧菌無效)cephamycin(對厭氧菌有效)依抗菌範圍分為第一、二、三及第四代,第一代Cephalosporins,有效範圍：以革蘭氏陽性細菌為主：MSSA、Streptococcus部分簡單的革蘭氏陰性桿菌：E.coli,Klebsiella,Proteus等。所有的cephalosporin對腸球菌(Enterococcus)均無效。Cephalothin、Cephalexin(Keflex)、Cefadroxil(Duracef)、Cephaloridin、Cephradin(Lofadine,Recef-A,U-save,Lacef)、Cefazolin(Cefamezin,Winzolin)等。,第一代Cephalosporins,RoutinesurgicalprophylaxisMethicillin-susceptibleS.aureusinfectionAnalternativeagentsforpenicillin-susceptibleS.pneumoniae,S.pyogenes,Viridansstreptococci.Community-acquiredgram-negativespathogensuchasE.coli,K.pneumoniae.Cellulitis,communityacquiredpneumoniaUTI,mildacutecholecystitis.,第二代CephalosporinsTruecephalosporin,有效範圍：對革蘭氏陰性細菌的活性增加如E.coli,Klebsiella,Proteus，對H.influenzae也有效。對革蘭氏陽性細菌中的MSSA較第一代差，對Streptococcus大致有效。對MRSA及Enterococcus無效。Cefaclor(Keflor)、Cefotiam(Pansporin)、Cefuroxime(Zinacef,Zinnant):0.75-1.5gmq6-8hrs,第二代CephalosporinsTruecephalosporin,UTI:尤其是可能或已知對第一代具抗藥性CommunitypneumoniaCOPDwith2ndinfection.Cefuroxime不建議用來治療腦膜炎,第二代Cephalosporinscephamycin,有效範圍：對革蘭氏陰性細菌的活性增加如E.coli,Klebsiella,Proteus，對H.influenzae也有效。對革蘭氏陽性細菌中的MSSA較第一代差，對Streptococcus大致有效。大部分的厭氧菌有效對MRSA及Enterococcus無效。Cefoxitin(Mefoxin,Lofatin)、Cefmetazole(Metacin):1gq6-8hrs,第二代Cephalosporinscephamycin,IntraabdominalinfectionsPeritonitis(原發性或次發性如盲腸炎破裂）IntraabdominalabscessPelvicinflammatorydisease,tuboovarianabscessSofttissueinfectionsPressuresoresDiabeticfootinfectionsAspirationpneumonia,Unasyn和2oCephalosporin的比較,第三代Cephalosporinsnon-anti-Pseudomonasagent,有效範圍具更強的對革蘭性陰性細菌的活性，對簡單的及較困難的陰性菌均有效。對MSSA無效，但Streptococcus則仍具效力。對MRSA及Enterococcus仍無效。對Pseudomonas無效Cefixime(Cefspan)、Cefpodoxime(Banan)、Cefotaxime(Claforan)、Ceftriaxone(Rocephin)、Ceftizoxime(Epocelin)、*Flomoxef(Flumarin),第三代Cephalosporinsnon-anti-Pseudomonasagent,MeningitisSalmonellainfectionGramnegativeSepsisGonorrheaSevereintraabdominalinfection:FlomoxefDrugresistantGramnegativebacilli,第三代CephalosporinsAnti-Pseudomonasagent,有效範圍具更強的對革蘭性陰性細菌的活性，對簡單的及較困難的陰性菌均有效。對MSSA無效，對Streptococcus效果差。對MRSA及Enterococcus仍無效。對Pseudomonas有效。Cefoperazone(Cefobid)、Ceftazidime(Fortum),第四代Cephalosporins,有效範圍：具更強的對革蘭性陰性細菌的活性，對簡單的及較困難的陰性菌均有效。對MSSA，Streptococcus均有效。對MRSA及Enterococcus仍無效。對Pseudomonas有效。Cefepime(Maxipime),Cefpirome,Monobactam,Aztreonam(Azactam)效力類同於：Anti-pseudomonas第三代cephalosporin但對所有格蘭氏陽性菌無效。對PenicillinorCephalosporin無交叉過敏性。Azactam1-2gmq8hrs.,Carbapenem,Imipenem(Tienam),Meropenem(Mepem)對各種格蘭氏陽性陰性菌及厭養菌均有效。但MRSA,腸球菌,Stenotrophomonasmaltophilia,Burkholderiacepacia具抗藥性。,Tienam,Imipenem-cilastatin(250/250,500/500mg)Cilastatin:避免imipenem被腎臟代謝維持imipenem的濃度減少imipenem的腎毒性Dosage500mgq6-8hrSideeffect:Seizure50y/oagewithsteroidesusages.atthefirstsignoftendonpainorinflammation,quitquinolone.,Precautioninuse,DonotuseinpatientswithhistoryallergictoquinolonesAvoiduseinchildren(50%GroupAstreptococcus30%MRSA:80%,MSSA:30-50%具抗藥性。台灣地區使用Macrolide多用於其他的Atypical的致病菌如Legionella,mycoplasma,Chlamydia等,ErythromycinAtypicalpneumoniaAcne500mgq6hpo,ivClarithromycinAtypicalpneumoniaHelicobacterpylori肺結核二線用藥Toxoplasmosis500mgq12hAzithromycinAtypiclpneumoniaChlamydiatrachomatis500mgonday1then250mgQDonday2-5,Clindamycin,Clindamycin,臨床用於：groupAstreptococci,MSSA,S.pneumoniae.厭氧菌：Bacteroidesfragilis,Clostridiumperfringens.Acnevulgaris.CNStoxoplasmosis,PneumocystiscariniiinAIDS.BabesiosisandmalariaSideeffect:rash,diarrhea,pseudomembranouscolitisClindamycin(Cleocin300mg/amp,150mg/tab)300-600mgq6hr,Chloramphenicol,Chloramphenicol,臨床上用於：因對bete-lactam藥物過敏病人的腦膜炎，Hinflenzae感染。BrainabscessRickettsial,Salmoneaaltyphi,Chlamydiapsittaciinfections,Toxicity:Bonemarrowsuppression,aplasticanemiaGray-babysyndrome,Metronidazole,Metronidazole,臨床用於：厭氧菌的感染如：Bacteroidesfragilis,其他Bacteroides,Clostridiumspp.,Fusobacterium,Peptococcus.抗生素引起Clostridiumdifficile感染之腹瀉。Parasites:Entamoebahistolytica(Amebiasis),Trichomoniasis,Giardiasis.HelicobacterbacterpyloriinpepticulcerdiseaseMetronidazole(Flagyl,Metronidazole,FrotinVag),Metronidazole,Dosage:250-500mgq6-8hrs肝臟代謝Sideeffects:Carcinogenicpotential:孕婦及嬰幼兒避免使用PeripheralneuropathyAnticoagulationinferferenceGIsymptoms:nausea,vomiting,abdominalpain,diarrhea.Metabolic,unpleasanttaste,Tetrecycline,Tetrecycline,用於Rickettsia、Chlamydia及Mycoplasma之感染。其他如：Lymedisease,Acne,Syphilis,Vibriospp。Sideeffect:Teethandbone:depressionofbonegrowthandgray-browndiscolorationoftheteethHepatitis,hypersensitivity,GItracteffects.Tetracyclin(Achromycin),Minocycline(Minocin),Doxycycline(Doryx),Trimethoprim-Sulfamethoxazole,(TMP-SMX),Trimethoprim-SulfamethoxazoleTMP-SMX,抗菌範圍Enterobacteriaceae:E.coli,P.mirabilis,Salmonella,ShigellaH.influenzaeB.catarrhalisGram(+):S.aureus,Streptococcuspneumoniae但台灣地區多已具抗藥性,Trimethoprim-SulfamethoxazoleTMP-SMX,臨床治療InfectivegastroenteritisUrinarytractinfectionCystitis,acutepyelonephritis,prostatitisPneumocystiscariniiinfectionNocardiaspp.StenotrophomonasmaltophiliaUTI:2#bid(1#=TMP80mg,SMX400mg)Severeinfection:15mg/kg/dayTMP,Linezolid:FirstAntibacterialfromaNewStructuralClass,Morpholinogroupenhancespharmacokineticprofile&improveswatersolubility,Strategicallylocatedfluorineatomimprovesactivity,C-5acylaminomethylgroupessential,5-(S)-configurationnecessary,N-Arylgrouprequired,ZYVOX:UniqueSiteofAction,InitiationFactors,30Sribosome,mRNA,50Sribosome,30S+mRNA,fMet-tRNA,ElongationFactors,70SInitiationComplex,PeptideProduct,Elongation,AminoglycosidesMacrolidesStreptogramins,Linezolidblocksformationoftheinitiationcomplex,Asia-PacificZAPS,Oralbioavailability,100%(basedonAUC),Foodeffect,NoeffectonextentSlightdecreaseinrate,Volumeofdistribution,50liters,Plasmaproteinbinding,31%,Eliminationhalf-life,6hours,PharmacokineticCharacteristicsofZyvox,Linezolid:DemonstratedClinicalEfficacy,Nosocomialpneumonia,includingMRSAHospitalizedpatientswithcommunity-acquiredpneumoniaSkinandsofttissueinfections,includingMRSAVancomycin-resistantEnterococcusfaeciuminfectionsatanysite,includingbacteremia,ZyvoxTM(linezolid)PackageInsert2001,ClinicalUseofZyvox,Zyvox(采福適)的核准適應症,因肺炎鏈球菌或金黃色葡萄球菌所引起的院內感染肺炎因肺炎鏈球菌或金黃色葡萄球菌所引起的社區感染肺炎，包括併發菌血症的病例因金黃色葡萄球菌、Spyogenes或Sagalactiae所引起的皮膚及軟組織的感染對萬古黴素有抗藥性的腸球菌感染，包括併發菌血症的病例,Zyvox(采福適)民國91年4月1日健保給付生效,給付規定:1)證實為MRSA感染，且證明為vancomycin抗藥菌株或使用vancomycin、teicoplanin治療失敗者或對vancomycin、teicoplanin治療無法耐受者2)證實為VRE感染，且無其他藥物可供選擇者3)骨髓炎及心內膜炎病患不建議使用4)其他抗藥性革蘭氏陽性菌感染，因病情需要，經感染症專科醫師會診確需使用者(申報費用時需檢附會診記錄相關之病例資料),Isoniazid(INH,H),Bactericidal(0.05-0.20ug/ml)Usualdose5mg/kg,Max:300mg/dayComplication:Hepatitis:themajortoxiceffectPeripheralneuropathy:morecommoninDM,uremia,alcoholism,malnutritionsupplypyridoxine10-25mg/dayInteractionwithphenytoin:monitorserumlevelofphenytoin,Rifampin(RMP,R),Bactericidial(0.5ug/ml)Usualdose10mg/kg/day,Max600mg/dayComplication:Gastrointestinalupset:themostcommonOrangecolorsecretion:urine,tears,sweat,andotherbodyfluids.Skinrasheruptions.Accelerateclearanceofdrugsmetabolizedbytheliver:methadone,coumadin,glucocorticoid,estrogens,oralhypoglycemicagents,digitalis,anticonvulsants,ketoconazole,andcyclosporin.hepatitis:4%Thrombocytopenia.,Ethambutol(EMB,E),Bacteriostatic15-25mg/kgComplication:球後視神經炎(Retrobularneuritis):themostfrequentandseriousadverseeffect視力模糊,中央盲點(centralscotomata)及紅綠色盲(red-greencolorblindness)八歲以下幼童宜避免使用Goutyarthritis,Pyraziamide(PZA,Z),bactericdialinanacidenvironment(pH50kg:RFN3002#QD50kg:RFN1503#QD,Azoles,Azole,Imidazole(MicronazoleandKetoco