Classification
PenicillinsCephalosporinsOther 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)
Mechanism of action
Inhibiton of bacterial cell wall synthesis
Target: PBPs(penicillin-binding proteins)
Cell-wall autolytic enzyme
Mechanism of resistanceInactivation of drug by β-lactamase
Trapping mechanism
Modification of PBPs
Impared penetration of drug to target PBPs
Absence of autolysins
PenicillinsHistory
Basic structure: 6-APA
ClassificationNatural penicillins
Semisynthesized penicillins
Penicillin G
ChemistryAntimicrobial activity
• Gram-positive cocciStreptococci ,pneumococci , staphylcocci
•Gram-positive rodsB.anthracis, diphtheriae, clostridium teran
i
Penicillin G
•Gram-negative cocciMeningococci, diplococcus gonorrhoeae
•Spirochetetreponema pallidum leptospirrosis
PharmacokineticsAbsorptionDistributionmetabolismExcretion
90% tubular secretion10% glomerular filtration
Clinical usesFirst choice for the following infections
Infection caused by streptococci, pneumococci, meningococci etc
Infection caused by spirochetes
Infection caused by gram-positive rods
Adverse reactionsAllergic reactions
Common: urticaria, fever,angioneurotic edema,eosinophlia, hemolytic anemiaSevere: anaphylactic shock
Herxheimer reaction
Allergic reactions Reason:degraded products of penicillin
Prevention: History of allergic reactions Skin test Epinephrine
Adverse reactions
Synthesized penicillinsAcid-resistant penicillinsPenicillinase-resistant penicillinsExtended-spectrum penicillinsExtended-spectrum penicillins against P.aeruginosaPenicillins against gram-negative bacteria
Acid-resistant penicillinsDrugs: penicillin V,phenethicillin
Character Orally effective, not resist β-Lactamase Lower potency than penicillin G
• Clinical uses: moderate infections
• Adverse reactions: allergic reaction
Penicillinase-resistant penicillins
Drugs:oxacillin, cloxacillin, dicloxacillin
Clinical use
Infection caused by penicillin-resistant staphylococci
Extended-spectrum penicillins
Ampicillin, amoxycillin, pivampicillin
Oral effective, susceptible to β-Lactamase
Broad spectrum: G+ G-
Clinical uses: infection caused by gram-negative rods
Extended-spectrum Penicillins against P.aeruginosa
Carbenicillin,sulbencillin, ticarcillin,
furbencillin, piperacillin, mezlocillin
• Character: more activity on P.aeruginosa
• Usually in combination with aminoglycosides
Penicillins against gram-negative bacteria
Mecillinam, pivmecillinam, temocillin
Narrow-spectrum:mainly on G- rods
β-Lactamase resistant
Treatment of infections caused by G- rods
CephalosporinsChemistry: 7-ACA
Classification: four generationsFirst-generation cephalosporinsSecond- generation cephalosporinsThird-generation cephalosporinsFourth- generation cephalosporins
First-generation cephalosporins
Cephazolin, cephalothin,cefradine,cefalexinCommon characters:Activity on gram-positive bacteria: first>secon
d>third Activity on gram-negative bacteria: first<secon
d<thirdStability to β-Lactamase produced by gram-neg
ative rods: first<second<thirdRenal toxicity: first>second>third
First-generation cephalosporins
Clinical uses
•Penicillin-resistant staphylococcal infection
•Minor to moderate infections caused by sensitive bacteria
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
Second-generation cephalosporins
Effective on anaerobesNo effect on P.aeruginosa
Clinical uses• Gram-negative bacteria infections
• Anaerobic infections
Third-generation cephalosporins
Ceftriaxone, ceftazidimeCommon 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
Third-generation cephalosporins
Clinical uses
a wide variety of serious infections caused by organisms that are resistant to most other drugs
Fourth- generation cephalosporins
Cefpirome,cefepime, cefclidinCharacter:• Enhanced antimicrobial activity
• Stable to ESBLs
• More activity on gram-positive cocci
• Clinical uses:• infections caused by organisms that are resis
tant to third-generation cephalosporins
Cephamycins
CefoxitinSimilar to third-generation cephalosporinsMore activity on anaerobesUsed to treat mixed anaerobic and aerobic infections
CarbapenemsThe most important antimicrobial agents in 1990’s
Wide spectrum and high activity
Resistant to mostβ-Lactamase(including ESBLs and cephalosporinase)
OxacephalosporinLatamoxef, flomoxef
Higher activity on anaerobes (especially Bacteroids fragilis)than third-generation cephalosporins
Well resitant to β-Lactamase
β-Lactamase inhibitors
Weak antimicrobial action
Protect β-lactams from inactivation by β-lactamase
Synergism