AntimicrobialAgents:GeneralConsideration

Antibiotics

AntibacterialdrugsThedrugsthatinhibitorkillthebacterialTheagentswhichareproducedbymicrobes,couldinhibitorkillothermicrobesChemotherapeuticindexA、ED90/LD10

B、ED50/LD50

C、LD90/ED50

D、LD50/ED50

E、LD95/ED5

MechanismofactionQuinolonesTetracyclinesAminoglycosides

Macrolides

ChloramphenicolLincomycinPolymyxinPolyenesAzoles

-lactamVancomycinDNAPlasmamembraneCellwallPABADHFATHFA50S50S50S30S30S30SmRNARifampinTMPSulfonamidesThemechanismofBacterialresistancetoantimicrobialagents：A.Productionofinactivator

B.DecreasedporinsofbacterialoutermembraneC.ModificationoftargetsitesD.IncreasedpermeabilityofbacterialoutermembraneE.Decreasedeffluxpumpβ－LactamAntibioticsPenicillinsCephalosporinsMonobactamsCarbapenemsBeta-LactaminhibitorsSection1Penicillinsβ-lactamase

nucleus：6-aminopenicillanicacid

(6-APA)

B：β－lactamringNSCOOR2ONHCR1OBAA：ThiazolidineBasicstructureofpenicillins一、Natruralpenicillin【Pharmacokinetics】intramuscularorintravenoustherapydistributetomosttissuesandserosa-linedcavities,lowconcentrationsappearincerebrospinalfluidPenicillinGisexcretedbythekidneys【Antibacterialactivity】Gram-positivecoccusGram-negativecoccusGram-positivebacilliHelicoidsGrampositivecoccus:staphylococci－Staphylococcusaureus、

Staphylococcusepidermidisstreptococcus－Streptococcushemolyticus、

StreptococcuspneumoniaeStreptococcusviridansGramnegativecoccus:Diplococcusmeningitides、Diplococcus

gonorrhoeaeGram-positivebacilliCorynebacterium

diphtheriaeCharbonSpore-FormingClostridiumtetani,Clostridiumperfringens,Penicillin【Mechanismofaction】1.Inhibitionoftranspeptidase:2.Increasedautoenzymeactivity【Clinicaluses】

1.InfectioncausedbyGrampositivecoccus

Staphylococci:

bouton,anthraciaandichorrhemia

Streptococcushemolyticus:pharyngitis,febris

rubra,

Streptococcuspneumoniae:pneumoniagenuina，

bronchialpneumonia

Streptococcusviridans：endocarditis，ichorrhemia

2.Cerebromeningitiscausedbydiplococcusmeningitides3.InfectioncausedbyGrampositivebacillitetanus,diphtheria,anthracnose4.Infectioncausedbyhelicoids

febris

hebdomadis,greatpox,relapsingfever【Adverseeffect】Allergy:

maculopapularrash,angioedemaandallergicshock.Antigenicdeterminant:penicilloicacidClinicalmanifestation:laryngealedema,bronchialspasm,lowbloodpressure,eclampsia,comaPreventionandcure

askhypersensitivehistorySkinsensitivitytestmustbedoneEpinephrineisfirstselectedtocureAllergicshock

Glucocorticoid,antihistaminedrugarealsochosenandsupplybloodvolume(1)Stimulate

receptor,decreasepermeabilityofbloodcapillary.(2)Stimulate

receptor,enhanceheartfunction,reliefbronchial

spasm.

2.HerxheimerreactionChill,fever,laryngalgia,headache,tachycardia.【Drugresistance】1.β-lactamaseactivity: Penicilinresistance:Penicillinase

Cephalosporins

resistance:ESBLsLactamaseinhibitorsresistance:AmpCtypeenzymeCarbapenemsresistance：Metalenzyme2.Alteredpenicillinbindingproteins

MRSA(Methicillin-resistantstrainsofstaphylococcusaureus)PRSP

(Penicillin-resistantstreptococcuspneumoniae)3.Decreasedpermeabilitytodrug

二、Semisyntheticpenicillin1.OralPenicillinPenicillinVhasaspectrumsimilartopenicillinG.Itismoreacid-stablethanpenicillinG.Itisoftenemployedinthetreatmentofupperrespiratoryinfectioncausedbygrampositivecoccus.MethicillinOxacillinnafillinCloxacillinDicloxacillinflucloxacillin2.Penicillinase-resistantpenicillin

Feature：

(1)Theykillpenicillinase-producingstaphylococci(2)Theycan’tkillMethicillin-resistantstrainsofStaphylococcusaureus(MRSA)(3)Theyareusedintreatmentofinfectionscausedby

penicillinase-producingstaphylococci3.Extendedspectrumpenicillins

Ampicillin

AmoxicillinFeature:(1)Theyaremoreeffectiveagainstgram-negativebacilli.(2)Theyareinactivatedby

-lactamases(3)Theytreaturinarytractinfections,sinusitis,

otitis,andlowerrespiratorytractinfections.(4)Theytreatinfectioncausedbypenicillin-resistancepneumococci(5)Ampicillincannottreatinfectioncausedbypseudomonasaeruginosa4.Antipseudomonal

penicillins:CarbenicillinPiperacillin

TheseantibioticshaveactivityagainstPseudomonasaeruginosa.Inadditiontheseantibioticsareeffectiveagainstmanygram-negativebacilli,butnotagainstpenicillinase-producingstaphylococci.Piperacillinisthemostpotent,andusedtotreatseriousinfectioncausedbybacillusproteusandpseudomonasaeruginosaFeature:

7-aminocephalosporanicacidNSCOOR2ONHCR1OBA

6-aminopenicillanicacidB：β－lactamringSection2Cephalosporins一、FirstgenerationcephalosporinCefalotin

CefazolinCefradineCefaloridine

TheyhavestrongactiveagainstGram-positivecocciTheyhavelessactiveagainstGram-negativebacteria;Theyareresistanttostaphylococcalproducingpenicillinase,butnotresistanttogramnegativebacilliproducingpenicillinase;【Featureofantibacterialactivity】

4.

TheyareineffectiveagainstPseudomonas

aeruginosaandanaerobic;5.TheyareusedtotreatinfectionbyGram-positivecocci.6.Theyarenephrotoxic二、SecondgenerationcephalosporinCefuroximeCefamandoleCefaclor【Featureofantibacterialactivity】TheyhaveactiveagainstGram-positivecocci,butantibacterialactionisweakerthanthatoffirstgeneration;Theyhaveextendedgram-negativebacilli,theiractionisstrongerthanfirstgeneration;Theyareresistanttogramnegativebacilliproducingpenicillinase;4.TheyareineffectiveagainstPseudomonasaeruginosa,buteffectiveagainstanaerobic;5.Theyoftenareusedtotreatsinusitis,otitis,lowerrespiratorytractinfections.6.Theyarelessnephrotoxic.CeftazidimeCeftriaxone

Cefoperazone

三、Thirdgenerationcephalosporin【Featureofantibacterialactivity】Theyhavestrongestactiveagainstgramnegativebacilliamongthreegenerations;TheyhaveweakestactiveagainstGram-positivecocciamongthreegenerations;Theyareresistanttogramnegativebacilliproducingbroad-spectrumβ-lactamase;4.TheyareeffectiveagainstPseudomonas

aeruginosaandanaerobic;5.Theyareusedtotreatawidevarietyofseriousinfectionscausedbyorganismsthatareresistanttomostotherdrugs.6Theyarenonephrotoxic.四、Fourthgenerationcephalosporin

Cefepime1.CefepimeisactiveagainstGram-positivecocci,aerobicGramnegativeorganisms;2.Itismoreresistanttochromosomalβ-lactamasese

andsomeextendedspectrumβ-lactamasese;3.ItmaybeusefulintreatmentofinfectioncausedbyGramnegativebacilliresistancetothirdgenerationcephalosporin,【Featureofantibacterialactivity】【Adverseeffectsofcephalosporins】1.Allergy:anaphylaxis,fever,skinrashes,nephritis,granulocytopenia,andhemolyticanemia2.Disulfiram-likeeffect:accumulationofacetaldehyde3.Bleeding:anti-vitaminKeffectsSection3Otherβ-lactamsantibioticsCarbapenemsMonobactams

β-lactamaseinhibitors一、CarbapenemsImipenemMeropenemPanipenem

Feature：ImipenemImipenemresistshydrolysisbymostβ

lactamases.2.Itisactiveagainstpenicillinase-producinggram-positiveandgram-negativeorganisms,anaerobes,Pseudomonasaeruginosa.3.Itundergoescleavagebyadehydropeptidase

foundinrena