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1、Introduction to Antibacterial TherapyClinically Relevant Microbiology and PharmacologyEdward L.Goodman,MDJuly 21,2003RationalelAntibiotic use(appropriate or not)leads to microbial resistancelResistance results in increased morbidity,mortality,and cost of healthcare lAppropriate antimicrobial steward
2、ship will prevent or slow the emergence of resistance among organisms(Clinical Infectious Diseases 1997;25:584-99.)lAntibiotics are used as“drugs of fear”(Kunin CM Annals 1973;79:555)Antibiotic MisuselSurveys reveal that:25-33%of hospitalized patients receive antibiotics(Arch Intern Med 1997;157:168
3、9-1694)22-65%of antibiotic use in hospitalized patients is inappropriate(Infection Control 1985;6:226-230)OutlinelBasic Clinical BacteriologylCategories of AntibioticslPharmacology of AntibioticsGoodmans Scheme for the Major Classes of Bacterial PathogenslGram Positive CoccilGram Negative RodslFasti
4、dious GNRlAnaerobesGram Positive CoccilGram stain:clusterslCatalase pos=StaphlCoag pos=S aureuslCoag neg=variety of specieslChains and pairslCatalase neg=streptococcilClassify by hemolysislType by specific CHOS.aureusPenicillin1950sPenicillin-resistantS.aureusEvolution of Drug Resistance in S.aureus
5、Methicillin1970sMethicillin-resistant S.aureus(MRSA)Vancomycin-resistantenterococci(VRE)Vancomycin1990s1997Vancomycinintermediate-resistantS.aureus (VISA)2002 Vancomycin-resistantS.aureusMSSA vs.MRSA Surgical Site Infections(1994-2000)Nosocomial Bloodstream IsolatesSCOPE ProjectSCOPE ProjectOther Ot
6、her(11%)(11%)Coagulase-Coagulase-negative negative staphylococci staphylococci(32%)(32%)Enterococci Enterococci(11%)(11%)All gram-All gram-negative negative(21%)(21%)Candida Candida(8%)(8%)Viridans Viridans streptococci streptococci(1%)(1%)Staphylococci Staphylococci aureusaureus(16%)(16%)Clin Infec
7、t Dis 1999;29:239-244Beta strept-continuedlS.agalactiae(Group B)Peripartum/NeonatalDiabetic footBacteremia/endocarditis/metastatic focilGroup D(non enterococcal)=S.bovisAssociated with carcinoma of colonViridans StreptococcilMany specieslStreptococcus intermedius group Liver abscessEndocarditisGI or
8、 pharyngeal floralMost other are mouth flora cause IEGram Negative RodslFermentorslOxidase negativelFacultative anaerobeslEnteric floralNumerous generaEscherischiaEnterobacterSerratia,etclNon-fermentorslOxidase positivelPure aerobeslPseudomonas and AcinetobacterNosocomialOpportunisticInherently resi
9、stantFastidious Gram Negative RodslNeisseria,Hemophilus,Moraxella,HACEKlRequire CO2 for growthlNeisseria must be plated at bedside Chocolate agar with CO2 Ligase chain reaction has reduced number of cultures for N.gonorrhea AnaerobeslGram negative rodsBacteroidesFusobacterialGram positive rodsClostr
10、idiaProprionobacterialGram positive cocciPeptostreptococci and peptococciAnaerobic Gram Negative RodslProduce beta lactamaselEndogenous floralPart of mixed infectionslConfer foul odorlHeterogeneous morphologylFastidiousAntibiotic Classificationaccording to Goodmanaccording to GoodmanlNarrow Spectrum
11、Active against only one of the four classeslBroad SpectrumActive against more than one of the classeslBoutiqueActive against a select number within a classNarrow SpectrumGPCGNRFastidAnaerVanc+-only clostridiaLinezolid+-Only gram posAG-+-Aztreon-+-Metro-+Broad SpectrumlActive against more than one cl
12、asslGPC and anaerobes:clindamycinlGPC and GNR:cephalosporins,penicillins,T/S,newer FQlGPC,GNR and anaerobes:ureidopenicillins BLI,carbapenemslGPC and fastidious:macrolidesPenicillinsStrepOSSAGNRFastidAnaerPen+-+/-+/-Amp/amox+-+/-+/-Ticar+-+/-+Ureid+-+BLI+Carba+Boutique AntibioticslJust like the Mall
13、 specialty storesspecialty drugslOften like the Mall stores in search of business;drugs in search of diseasesSynercid for VRE faecium,not faecalis,MRSALinezolid VRE,MRSAlID consult neededPharmacodynamicslMIC=lowest concentration to inhibit growth lMBC=the lowest concentration to killlPeak=highest se
14、rum level after a dose lAUC=area under the concentration time curvelPAE=persistent suppression of growth following exposure to antimicrobialTime over MIClShould exceed MIC for at least 50%of dose intervallHigher doses may allow adequate time over MIClFor most beta lactams,optimal time over MIC can b
15、e achieved by continuous infusion(except unstable drugs such as imipenem,ampicillin)Higher Serum/tissue levels are associated with faster killing lAminoglycosides Peak/MIC ratio of 10-12 optimal Achieved by“Once Daily Dosing”PAE helpslFluoroquinolones 10-12 ratio achieved for enteric GNRlPAE helps n
16、ot achieved for Pseudomonas nor Streptococcus pneumoniae AUC/MIC=AUIClFor Streptococcus pneumoniae,FQ should have AUIC=30lFor gram negative rods where Peak/MIC ratio of 10-12 not possible,then AUIC should=125.Antibiotic Use and Resistancel-Strong epidemiological evidence that antibiotic use in human
17、s and animals associated with increasing resistancel-Subtherapeutic dosing encourages resistant mutants to emerge;conversely,rapid bactericidal activity discouragesl-Hospital antibiotic control programs have been demonstrated to reduce resistanceTotal Antibiotic Doses/DayChanges in Bug/Drug Suscepti
18、bility PatternsFurther Activities of CAMPlDecrease inappropriate fluoroquinolone useStaff educationRestricted reporting lDecrease inappropriate sputum culturesStaff education Laboratory disclaimer lDecrease inappropriate vancomycin levelsEducation about unnecessary peak levels Further Activities of
19、CAMPlMonitor surgical site infections and intervene as necessaryImproved timing and administration of pre-op antibioticsclipping not shavingnasal decolonizationchanging pathogens(MRSA,gram-rods)lAutomated protocol-driven antibiotic prescribingComputerized physician order entry Antibiotic Armageddon“
20、There is only a thin red line of ID practitioners who have dedicated themselves to rational therapy and control of hospital infections”Kunin CID 1997;25:240Historic overview on treatment of infectionsl2000 BC:Eat this rootl1000 AD:Say this prayerl1800s:Take this potionl1940s:Take penicillin,it is a miracle drugl1980s:Take this new antibiotic,it is betterl?2003 AD:Eat this root