1. β-Lactam antibiotics

2. Classification Penicillins Cephalosporins Other β-Lactam drugs Cephamycins （头霉素类） Carbapenems （碳青霉烯类） Oxacephalosporins （氧头孢烯类） β-Lactamase inhibitors （ β- 内酰胺酶抑制剂） Monolactums （单环 β- 内酰胺类）

3. Mechanism of action Inhibiton of bacterial cell wall synthesis Target: PBPs(penicillin-binding proteins) Cell-wall autolytic enzyme

4. Mechanism of resistance Inactivation of drug by β-lactamase Trapping mechanism Modification of PBPs Impared penetration of drug to target PBPs Absence of autolysins

5. Penicillins History Basic structure: 6-APA Classification Natural penicillins Semisynthesized penicillins

6. Penicillin G Chemistry Antimicrobial activity Gram-positive cocci  Streptococci,pneumococci, staphylcocci Gram-positive rods  B.anthracis, diphtheriae, clostridium terani

7. Penicillin G Gram-negative cocci  Meningococci, diplococcus gonorrhoeae Spirochete  treponema pallidum leptospirrosis

8. Pharmacokinetics Absorption Distribution metabolism Excretion 90% tubular secretion 10% glomerular filtration

9. Clinical uses First choice for the following infections Infection caused by streptococci, pneumococci, meningococci etc Infection caused by spirochetes Infection caused by gram-positive rods

10. Adverse reactions Allergic reactions Common: urticaria, fever,angioneurotic edema,eosinophlia, hemolytic anemia Severe: anaphylactic shock Herxheimer reaction

11. Allergic reactions  Reason :degraded products of penicillin  Prevention:  History of allergic reactions  Skin test  Epinephrine Adverse reactions

12. Synthesized penicillins Acid-resistant penicillins Penicillinase-resistant penicillins Extended-spectrum penicillins Extended-spectrum penicillins against P.aeruginosa Penicillins against gram-negative bacteria

13. Acid-resistant penicillins Drugs: penicillin V,phenethicillin Character  Orally effective, not resist β-Lactamase  Lower potency than penicillin G Clinical uses: moderate infections Adverse reactions: allergic reaction

14. Penicillinase-resistant penicillins Drugs: oxacillin, cloxacillin, dicloxacillin Clinical use Infection caused by penicillin- resistant staphylococci

15. Extended-spectrum penicillins Ampicillin, amoxycillin, pivampicillin Oral effective, susceptible to β-Lactamase Broad spectrum: G + G - Clinical uses: infection caused by gram-negative rods

16. Extended-spectrum Penicillins against P.aeruginosa Carbenicillin,sulbencillin, ticarcillin, furbencillin, piperacillin, mezlocillin Character: more activity on P.aeruginosa Usually in combination with aminoglycosides

17. Penicillins against gram- negative bacteria Mecillinam, pivmecillinam, temocillin Narrow-spectrum:mainly on G - rods β-Lactamase resistant Treatment of infections caused by G - rods

18. Cephalosporins Chemistry: 7-ACA Classification: four generations  First-generation cephalosporins  Second- generation cephalosporins  Third-generation cephalosporins  Fourth- generation cephalosporins

19. First-generation cephalosporins Cephazolin, cephalothin,cefradine,cefalexin Common characters:  Activity on gram-positive bacteria: first>second>third  Activity on gram-negative bacteria: first<second<third  Stability to β-Lactamase produced by gram- negative rods: first<second<third  Renal toxicity: first>second>third

20. First-generation cephalosporins Clinical uses Penicillin-resistant staphylococcal infection Minor to moderate infections caused by sensitive bacteria

21. Second-generation cephalosporins Cefamandole, cefuroxime,cefaclor Common characters  More stable to β-Lactamase  More active on gram-negative bacteria  Less active on gram-positive bacteria  Less renal toxicity

22. Second-generation cephalosporins  Effective on anaerobes  No effect on P.aeruginosa Clinical uses Gram-negative bacteria infections Anaerobic infections

23. Third-generation cephalosporins Ceftriaxone, ceftazidime Common characters Much more active on gram-negative bacteria Stable to extended β-Lactamase produced by gram-negative bacteria Effective on anaerobes and P.aeruginosa No renal toxicity Penetrating body fluids and tissues well

24. Third-generation cephalosporins Clinical uses a wide variety of serious infections caused by organisms that are resistant to most other drugs

25. Fourth- generation cephalosporins Cefpirome,cefepime, cefclidin Character: Enhanced antimicrobial activity Stable to ESBLs More activity on gram-positive cocci Clinical uses: infections caused by organisms that are resistant to third-generation cephalosporins

26. Other β-Lactam drugs

27. Cephamycins Cefoxitin Similar to third-generation cephalosporins More activity on anaerobes Used to treat mixed anaerobic and aerobic infections

28. Carbapenems The most important antimicrobial agents in 1990’s Wide spectrum and high activity Resistant to mostβ- Lactamase(including ESBLs and cephalosporinase)

29. Carbapenems Thienamycin Imipenem Imipenem-cilastatin:tienam Meropenem Panipenem

30. Oxacephalosporin Latamoxef, flomoxef Higher activity on anaerobes (especially Bacteroids fragilis)than third-generation cephalosporins Well resitant to β-Lactamase

31. β-Lactamase inhibitors Clavulanic acid Sulbactam tazobactam

32. β-Lactamase inhibitors Weak antimicrobial action Protect β-lactams from inactivation by β-lactamase Synergism

33. Monobactams Aztreonam, carumonam No effect on gram-positive bacteria and anaerobes High activity on gram-negative bacteria Penicillin-allergic patients tolerate well Low toxcity