β-内酰胺酶抑制剂抗生素的使用及作用机理(英文)β-Lactam-antibiotics课件.ppt

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1、-Lactam antibioticsClassificationPenicillinsCephalosporinsOther-Lactam drugsCephamycins（头霉素类）Carbapenems（碳青霉烯类）Oxacephalosporins（氧头孢烯类）-Lactamase inhibitors（-内酰胺酶抑制剂）Monolactums（单环-内酰胺类）Mechanism of actionInhibiton of bacterial cell wall synthesisTarget:PBPs(penicillin-binding proteins)Cell-wall aut

2、olytic enzymeMechanism of resistanceInactivation of drug by-lactamaseTrapping mechanismModification of PBPsImpared penetration of drug to target PBPsAbsence of autolysinsPenicillin GChemistryAntimicrobial activity Gram-positive coccisStreptococci,pneumococci,staphylcocciGram-positive rodssB.anthraci

3、s,diphtheriae,clostridium terani Penicillin GGram-negative coccisMeningococci,diplococcus gonorrhoeaeSpirochetestreponema pallidum leptospirrosisPharmacokineticsAbsorptionDistributionmetabolismExcretion90%tubular secretion10%glomerular filtrationAdverse reactionsAllergic reactionsCommon:urticaria,fe

4、ver,angioneurotic edema,eosinophlia,hemolytic anemiaSevere:anaphylactic shockHerxheimer reactionAllergic reactionsv Reason:degraded products of penicillinv Prevention:v History of allergic reactionsv Skin testv EpinephrineAdverse reactionsAcid-resistant penicillinsDrugs:penicillin V,phenethicillinCh

5、aracterOrally effective,not resist-Lactamase Lower potency than penicillin GClinical uses:moderate infectionsAdverse reactions:allergic reactionExtended-spectrum penicillinsAmpicillin,amoxycillin,pivampicillinOral effective,susceptible to-Lactamase Broad spectrum:G+G-Clinical uses:infection caused b

6、y gram-negative rodsExtended-spectrum Penicillins against P.aeruginosaCarbenicillin,sulbencillin,ticarcillin,furbencillin,piperacillin,mezlocillinCharacter:more activity on P.aeruginosaUsually in combination with aminoglycosidesCephalosporinsChemistry:7-ACAClassification:four generationsFirst-genera

7、tion cephalosporinsSecond-generation cephalosporinsThird-generation cephalosporinsFourth-generation cephalosporinsFirst-generation cephalosporinsCephazolin,cephalothin,cefradine,cefalexinCommon characters:Activity on gram-positive bacteria:firstsecondthird Activity on gram-negative bacteria:firstsec

8、ondthirdStability to-Lactamase produced by gram-negative rods:firstsecondsecondthirdFirst-generation cephalosporinsClinical usesPenicillin-resistant staphylococcal infectionMinor to moderate infections caused by sensitive bacteria Second-generation cephalosporinsCefamandole,cefuroxime,cefaclorCommon

9、 charactersv More stable to-Lactamasev More active on gram-negative bacteriav Less active on gram-positive bacteriav Less renal toxicitySecond-generation cephalosporinsvEffective on anaerobesvNo effect on P.aeruginosaClinical usesGram-negative bacteria infectionsAnaerobic infectionsThird-generation

10、cephalosporinsClinical uses a wide variety of serious infections caused by organisms that are resistant to most other drugsFourth-generation cephalosporinsCefpirome,cefepime,cefclidinCharacter:Enhanced antimicrobial activityStable to ESBLsMore activity on gram-positive cocciClinical uses:infections

11、caused by organisms that are resistant to third-generation cephalosporins Other-Lactam drugsCarbapenemsThe most important antimicrobial agents in 1990sWide spectrum and high activityResistant to most-Lactamase(including ESBLs and cephalosporinase)CarbapenemsThienamycin ImipenemImipenem-cilastatin:ti

12、enamMeropenemPanipenem-Lactamase inhibitorsClavulanic acid Sulbactamtazobactam-Lactamase inhibitorsWeak antimicrobial actionProtect-lactams from inactivation by-lactamaseSynergismMonobactamsAztreonam,carumonamNo effect on gram-positive bacteria and anaerobesHigh activity on gram-negative bacteriaPenicillin-allergic patients tolerate wellLow toxcity