-Lactam antibiotics

Classification
Penicillins Cephalosporins Other -Lactam drugs
Cephamycins Carbapenems Oxacephalosporins -Lactamase inhibitors - Monolactums-

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

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

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

Penicillin G
Chemistry Antimicrobial activity Gram-positive cocci
Streptococci ,pneumococci , staphylcocci

Gram-positive rods
B.anthracis, diphtheriae, clostridium terani

Penicillin G
Gram-negative cocci
Meningococci, diplococcus gonorrhoeae

Spirochete
treponema pallidum leptospirrosis

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

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

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

Herxheimer reaction

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

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

Acid-resistant penicillins
Drugs: penicillin V,phenethicillin Character
Orally effective, not resist -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 penicillinresistant staphylococci

Extended-spectrum penicillins
Ampicillin, amoxycillin, pivampicillin
Oral effective, susceptible to -Lactamase

Broad spectrum: G+ GClinical 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 gramnegative bacteria

Mecillinam, pivmecillinam, temocillin Narrow-spectrum:mainly on G- rods -Lactamase resistant Treatment of infections caused by Grods

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

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 -Lactamase produced by gramnegative rods: first<second<third Renal 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 -Lactamase More active on gram-negative bacteria Less active on gram-positive bacteria Less renal toxicity

Second-generation cephalosporins
Effective on anaerobes No effect on P.aeruginosa

Clinical uses

Gram-negative bacteria infections Anaerobic infections

Third-generation cephalosporins
Ceftriaxone, ceftazidime Common characters

Much more active on gram-negative bacteria Stable to extended -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, cefclidin Character:

Enhanced antimicrobial activity Stable to ESBLs More activity on gram-positive cocci

infections caused by organisms that are
resistant to third-generation cephalosporins

Clinical uses:

Other -Lactam drugs

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

Carbapenems
The most important antimicrobial agents in 1990s Wide spectrum and high activity Resistant to mostLactamase(including ESBLs and cephalosporinase)

Carbapenems
Thienamycin Imipenem Imipenem-cilastatin:tienam Meropenem Panipenem

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

-Lactamase inhibitors
Clavulanic acid Sulbactam tazobactam

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

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