（抗生素教学讲解课件）Introduction-for-Antibiotics.ppt

1、Introduction for Antibiotics R3 孔祥琪孔祥琪Last revised:July 6,2003Section of Infectious DiseasesDepartment of Internal Medicine National Taiwan University Hospital,Taipei臨床上常見的致病微生物 Bacteria Viruses Fungi Mycobacterium Mycoplasma Protozoa臨床上常見的致病菌nAerobicnGram-positive bacterianGram-negative bacterianAn

2、aerobicnGram-positive bacterianGram-negative bacteriaAerobic Gram-positive bacterianCoccinStaphylococcus spp.nStreptococcus spp.nEnterococcus spp.nBacillinListeria spp.nBacillus spp.StaphylococcinCoagulase-positivenStaphylococcus aureusnCoagulase-negativenStaphylococcus epidermidisnStaphylococcus sa

3、prophyticusnStaphylococcus haemolyticusnMethicillin-resistantnMRSAnMRCNSnMethicillin-sensitivenMSSAnMSCNSStreptococci(1)Classification Lancefield:based on the antigenic characteristics of the outer membrane Brown:type of hemolysis Clinical:combines Lancefield,Brown,disease producing charactersticsSt

4、reptococci(2)nalpha hemolysisincomplete hemolysisS.viridans and S.pneumoniaenbeta hemolysiscomplete hemolysisGroup A Strep =S.pyogenesnGamma hemolysisnonhemolyticSome Group D Strep.nS.pyogenes(Group A,hemolytic)Pharyngitis ImpetigonViridans group(alpha hemolytic)EndocarditisnS.pneumoniae(Pneumococcu

5、s)Bacteremia Pneumonia MeningitisGram-positive bacillinBacillus cereusnDiptheroids Corynebacterium diptheriae JK group Corynebacterium Listeria monocytogenesAerobic Gram-negative bacterianBacillinEnterobacteriaceaenNFGNB:Glucose Non-fermentative Gram-negative bacillinHaemophilus species(H.influenzae

6、;H.parainfluenzae)nLegionella pneumophilia nCoccinNeisseria gonorrhoeae(gonococcus)nNeisseria meningitidis(meningococcus)nMoraxella catarrhalis Gram-negative bacteriaEnterobacteriaceaeE.coliKlebsiella spp.Proteus spp.Salmonella spp.Shigella spp.Enterobacter spp.Citrobacter spp.Serratia spp.Edwardsie

7、lla spp.Yersinia spp.NFGNB Pseudomonas aeruginosaAcinetobacter baumanniiStenotrophomonas maltophilia (Pseudomonas maltophilia)Burkholderia cepacia(Pseudomonas cepacia)Anaerobic bacterianGram-positivenCoccinStreptococcus,GemellanPeptococcus,PeptostreptocuccusnBacillinClostridium(C.perfringes,C.tenani

8、,C.difficile,C.botulinum)nPropionibacteriumnBifidobacteriumnLactobacillusnGram-negativenBacillinFusobacteriumnBacteroides nPrevotellanCampylobacter nCocci臨床上常見的致病菌nGram-positive bacterianStaphylococcus aureus nStreptococcusnEnterococcusnGram-negative bacterianE.coli,Klebsiella,Proteus(EKP)nEnterobac

9、ter,SerratianNon-fermentative Gram-negative bacilli(NFGNB)nHaemophilus influenzaenMeningococcusnAnaerobic bacterianBacteroides fragilisnOthers-Lactam antibioticsnPenicillinnCephemnCephalosporinnCephamycinnMonobactamnCarbapenemn-lactam/-lactamase inhibitorPenicillinsnNatural penicillinsnPenicillin G(

10、IV)nPenicillin V(oral)nPenicillinase-resistant penicillinsnOxacillin(IV),MethicillinnDicloxacillin(oral)nBroad-spectrum penicillinsnAmpicillin(IV,oral)nAmoxicillin(oral)nExtended-spectrum penicillinsnCarbenicillin(IV,oral)nTicarcillin(IV)nPiperacillin(IV)Natural PcPcnase-RBroad PcExtended PcGram(+)S

11、taph MSSA -+-MRSA -Streptococcus +Enterococcus +-+Gram(-)E.coli,Kleb -+Enterobacter -+Pseudomonas -+Haemophilus -+(-)Anaerobic Bacteroides -lactam/-lactamase inhibitorsnClinically usednClavulanic acidnSulbactamnTazobactamnSpecial notesnNo antibacterial activitynNever used alone-lactam+-lactamase inh

12、ibitorAmpicillin+Sulbactam =UnasynAmoxicillin+Clavulanic acid =AugmentinTicarcillin+Clavulanic acid =TimentinPiperacillin+Tazobactam =TazocinAmpicillinUnasynAmoxicillinAugmentinGram(+)Staph MSSA -+MRSA -Streptococcus +Enterococcus +Gram(-)E.coli,Kleb +(-)+Enterobacter -Pseudomonas -Haemophilus -+Ana

13、erobic Bacteroides -+TicarcillinTimentinPiperacillinTazocinGram(+)Staph MSSA -+MRSA -Streptococcus +Enterococcus +Gram(-)E.coli,Kleb +(-)+Enterobacter +Pseudomonas +(-)+(-)Haemophilus +(-)+Anaerobic Bacteroides -+CephemsnFirst-generation cephemnCefazolin(IV),Cephalexin(oral)nSecond-generation cephem

14、nAbove diaphragm:Cefuroxime(IV,oral),Cefotiam(IV)nBelow diaphragm:Cefoxitin,cefmetazole(IV cephamycin)nThird-generation cephemnWithout antipseudomonal activitynWith antipseudomonal activitynFourth-generation cephemnCefepime,CefpiromeFirst-generation cephemsnCefazolinnActivity:nMSSA,StreptococcusnE.c

15、oli,K.pneumoniae,P.mirabilisnIneffective:nEnterococcus,anaerobesnOther GN bacteriaSecond-generation cephemsnTrue cephems:nCefotiam,cefuroxime,cefaclornEnhance the anti-GNB effect of 1st cephemsnLess effective for GPCnCephamycins:nCefmetazole,cefoxitinnWith the effect for anaerobesnIneffective:nMRSA,

16、Enterococcus,other GNBThird-generation cephems(1)nTrue cephem:ncefotaxime,ceftriaxone,ceftazidimenCephamycin:flomoxefnActivity:nAround 50%for MSSAnEnhanced activity for streptococcusnStrong effect for EnterobactereaceanCeftazidime and cefoperazone are also effective for P.aeruginosaThird-generation

17、cephems(2)nFlumarin(flomoxef)nEffective for anaerobes and most MSSAnIneffective:nMRSA,EnterococcusnMore resistant Enterobactereacea,such as Enterobacter,Citrobacter,Serratia,Morganella(若為有效,應combine aminoglycosides)Fourth-generation cephemsnCefepime,cefpiromenActivity:nMost MSSA,StreptococcusnMost e

18、nterobactereacea,including Enterobacter,Citrobacter,Serratia,MorganellanPseudomonas aeruginosanIneffective:nEnterococcus,MRSAnAnaerobes 1 2 2 3 3(+)cephem cephalosporin cephamycin cephem cephemGram(+)Staph MSSA +-MRSA -Streptococcus +Enterococcus -Gram(-)E.coli,Kleb -+Enterobacter -+Pseudomonas -+Ha

19、emophilus -+Anaerobic Bacteroides -+-MonobactamnOnly one drug:aztreonamnActivity:nMost GNB,including P.aeruginosanIneffective:nGP bacteria,anaerobesnSpecial consideration:nlactam allergy&impairing renal functionCarbapenemsnImipenem&meropenemnActivity:nAlmost all bacteria are susceptiblenIneffective:

20、nMRSA,Enterococcus faceium,Burkholderia cepaciae,Stenotrophomonas maltophilianSpecial consideration:nMeropenem is preferred in CNS infectionMonobactamCarbapenemGram(+)Staph MSSA -+MRSA -Streptococcus -+Enterococcus -+Gram(-)E.coli,Kleb +Enterobacter +Pseudomonas +Haemophilus +Anaerobic Bacteroides -

21、+Exception:(1)MRSA(2)Enterococcus faecium(3)Stenotrophomonas maltophilia(4)Burkholderia cepaciaMonobactam(Aztreonam);Carbapenem(Imipenem+Cilastatin sodium;Meropenem)Classification of QuinolonesnFirst generationnNalidixic acidnOxolinic acidnCinoxacinnSecond generationnNorfloxacinnCiprofloxacinnEnoxac

22、innLomefloxacinnOfloxacinnThird generationnLevofloxacinnSparfloxacinnGatifloxacinnGrepafloxacinnFourth generationnTrovafloxacinnMoxifloxacinFluoroquinolonesnActivity:nMSSA,some enterococcus,most GNB(salmonella&shigella)mycobacterium,clamydia,mycoplasma,legionella,dipheria,pertusisn3rd-generation hav

23、e the effect for streptococcus,anaerobesnIneffective:MRSAFluoroquinolonesnSpecial consideration:nOne step mutation results in resistancenCross resistance is a common phenomenonnCiprofloxacin is not effective for streptococcus in vivonSignificant hepatotoxicity:trovafloxacin,grepafloxacinnSignificant

24、 photosensitivity:sparfloxacin,clinafloxacinnSignificant cardiac adverse effect:grepafloxacin(QTc)nSignificant CNS excitatory effect:clinafloxacinFluoroquinolonePathogen GNB NFGNB GPC Atypical Anaerobic1st generation Pipemidic acid(Dolcol)+-2nd generation Ciprofloaxin(Cirpoxin)+-+-Norfloxacin(Baccid

25、al)3rd generation Levofloxacin(Cravit)+/-Moxifloxacin(Avelox)Gatifloxacin4th generation Trovafloxacin +SparfloxacinAminoglycosidesnStreptomycinnKanamycinnGentamicinnTobramycinnNetilmicinnAmikacinnAnti-Gram-negative bacterianCould be used alone,but seldom used alonenIn combination with other antibiot

26、icsn-lactam+aminoglycosideAminoglycosidesnDrugs:nGentamicin,tobramycin,amikacinnActivity:nMost bacterianIneffective:H.influenzae&anaerobesnSpecial consideration:nNot active in anaerobic and acidic areanOnce daily regimennSynergism with lactamsAminoglycosidesnAnti-Gram-positive bacterianHas anti-Gram

27、-positive activity,but never used alone for Gram-positive infectionnIn combination with other antibioticsnInfective endocarditisnPenicillin G+gentamicinnEnterococcus infectionnAmpicillin+gentamicinnStaphylococcus infectionnOxacillin+gentamicinnVancomycin+gentamicinAminoglycosidesnThe only bactericid

28、al agent among protein synthesis inhibitorsnAlways used in combination therapy:nWith-lactam and glycopeptides:the best synergistic effectsnWith clindamycin and metronidazole for mixed infectionsnWith quinolones:additive?antagonism?synergism?nNot penetrating BBBnImportant indications:nSevere aerobic

29、Gm(-)bacilli bacteremianFor treatment of Pseudomonas,Enterobacter,Serratia,Enterococcus,Streptococcal endocarditisnEmergence of resistance during therapy is rareAnti-Gram-Positive AntibioticsnGlycopeptides(Vancomycin,Teicoplanin)nMainly anti-Gram-positive activitynStreptogramins(Quinupristin/dalfopr

30、istin,Synercid)nAntibiotic-resistant GPC,esp.VRE,MRSA,VISA,and antibiotics-resistant strains of S.pneumoniae nOxazolidinones(Linezolid,Zyvox)nAerobic andanaerobic GP bacteria,including VRE,MRSA,antibiotics-resistant strains of S.pneumoniae GlycopeptidesnVancomycin,teicoplaninnActivity:nMost GP bacte

31、ria,including anaerobesnIn vitro,effective for Chryseobacterium meningosepticumnIneffective:nAlmost all GN bacterianGP bacteria only:nLeukonostoc and PediococcusGlycopeptidesnVancomycin compared with teicoplanin:nGenerally,recognized as the same effectnBenefits:nSerum level as the guide of dosagenCo

32、uld combined with rifampinnShortage:nShould be infused at 500 mg/hour with large amount of fluid-red man syndromenRenal toxicity and ototoxicitynIneffective for Van B phenotype VRENew anti-GP AntibioticsnNew anti-GP antibiotics:nFusidic acidnQuinupristin/dalfopristin(Synercid)nOxazolidinones:eperezo

33、lid,linezolid(Zyvox)nActivity:nAlmost all GP bacteria,including MRSAnSynercid and Zyvox are also effective for VREnFusidic acid is also effective for H.influenzae and M.catarrhalisMarcolidesnErythromycinnRoxithromycinnClarithromycinnAzithromycinNew marcolidesNew marcolides v.s.ErythromycinnSimilar a

34、ntibacterial activitynBetter pharmacokineticsnLonger half life(qd or bid)nHigher intracellular concentrationnLess side effect,especially GI side effectMacrolidesn“Old”macrolides:erythromycinn“New”macrolides:nClarithromycin,roxithromycin,azithromycinnActivity:nGPC:MSSA&S.pneumoniae(not in Taiwan)nB.p

35、ertusis,C.diphtheria,L.pneumophila,M.pneumoniae,syphilis,Chlamydia,U.urealyticum,Campylobacter,Helicobacter,NTM.MarcolidesnAnti-Gram-positive activityStaphylococcusStreptococcusMSSAMRSAPneumoGroup AR:3050%80%90%30%nAnti-atypical-pathogensnMycoplasmanLegionellanChlamydiaFluoroquinoloneVancomycinMarco

36、lideGram(+)Staph MSSA +-+MRSA -+-+Streptococcus +-+Enterococcus +-+Gram(-)E.coli,Kleb +-Enterobacter +-Pseudomonas +-Haemophilus +-Anaerobic Bacteroides -Sulfa drugsnSulfamethoxazole+Trimethoprim(Co-trimoxazole)(Baktar,Septrim)nClinical applicationsnSimple UTInPneumocystis carinii infectionnTraveler

37、 diarrheanSalmonellosisnSuppression therapy of MRSA infectionsnPneumocystis carinii infectionsnToxoplasmosisnInflammatory bowel diseasesTetracyclinesnTetracycline,Minocycline,Doxycycline q6h q12h q24hnIndicationsnMycoplasma infectionnChlamydia infectionnRickettsial infectionnScrub typhus(Tsutsugamus

38、hi disease)nQ fevernDrug of choice for CAP(not in Taiwan)nRickettsial infectionsnEffective for Vibrio spp.Metronidazole,Chloramphenicol,ClindamycinnAnti-anaerobic drug(cephamycin,-lactam+-lactamase inhibitor,carbapenem,metronidazole,clindamycin)nMetronidazolenAmeba,Trichomonas infectionnPseudomembra

39、ne colitis(Clostridium difficile)nClindamycinnAnti-Gram-positive alternative agentOther AntibioticsnClindamycin:nMSSA,some CNS,Gr.A Streptococcus,GP anaerobesnWell-penetration to bonenMetronidazole:nGN anaerobes,C.difficile (Pseudomembrane colitis)nAmeba and some other parasitesnChloramphenicol:bone

40、 marrow suppressionDrug of choiceAlternative(1)Alternative(2)Gram(+)Staph MSSAOxacillin1 cephem Vancomycin MRSAVancomycinTeicoplaninStreptococcusPenicillin GCephalosporinVancomycinEnterococcusAmpicillin,Pc GVancomycinGram(-)E.coli,KlebCephalosporin-lactamase inhibitorFluoroquinoloneEnterobacter?PseudomonasExtended Pc,3 cephemMonobactamFluoroquinoloneHaemophilusAmpicillin-lactamase inhibitor2 cephemAnaerobic BacteroidesMetronidazole,clindamycin-lactamase inhibitorCephamycin