1. Pharmacology of Cephalosporins: General Overview
Flavio Guzmán, M.D.

2. β- lactams: cell wall inhibitors
Penicillins
Cephalosporins
Carbapenems
Monobactams

3. β-lactam ring The β-lactam ring is a common structure for: Penicillins
Cephalosporins
Monobactams
Carbapenems
Bacteria will target this ring to gain resistance.

4. Cell wall inhibitors: important features
Cell wall inhibitors have bacericidal effect.
They act sinergistically with amynoglycosides
Time-dependent kinetics: the more time the drug binds the bacteria, the more effective it is.
or instance, certain antibiotics, like beta-lactams (penicillins, cephalosporins, carbapenems, monobactams), clindamycin, macrolides (erythromycin, clarithromycin), oxazolidinones (linezolid), can be effective because of the extensive amount of time the antibiotic binds to the microorganism. The inhibitory effect can be effective because their concentration exceeds the MIC for the microorganism.

5. Mechanism of action 1
Beta-lactams bind PBP (Penicillin Binding Proteins).
Some PBP have transpeptidase activity.
Transpeptidase activity is essential in cell wall synthesis.

6. Mechanism of action 2 Transpeptidation inhibition
Autolysins production
Cell wall destruction

7. Cephalosporins 4th gen Cefepime 1st gen 2nd gen 3rd gen Cefadroxil
Cefazolin
Cephalexin
Cephalothin
2nd gen
Cefaclor
Cefoxitin
Cefuroxime sodium
Cefuroxime axetil
3rd gen
Cefnidir
Cefixime
Cefotaxime
Ceftazidime
Ceftibuten
Ceftriaxone
4th gen
Cefepime

8. Cephalosporins: characteristics
As beta-lactams
Mechanism of action
Bactericidal
¿Bactericidal or bacteriostatic?
Different, according to generations
Antibiotic coverage

9. Chemical structure of cephalosporins
Derived from 7-aminocephalosporanic acid.
They suffer the “attack” of bacteria at their beta-lactam ring.

10. First gen. cephalosporins.:
Cephalexin (prototype)
Cefadroxil
Parenteral
Cephalotin
Cefazolin

11. 1st Generation cephalosporins: antibacterial coverage
Active mainly against Gram positive cocci.
Less active against Gram negative.
Methicillin-sensitive Staphylococcus aureus
Coagulase +,-
Streptococcus
Gram +
PEcK: Proteus, E. Coli, Klebsiella
Gram -

12. Clinical uses of first gen. cephalosporins
Impetigo
Caused by: Staphylococcus aureus and Streptococcus pyogenes
Celullitis
Group A streptococcus bacterium (Streptococcus pyogenes, GAS) and Staphylococcus aureus
Prophylaxis of surgical wound infections
Mainly produced by Gram positive bacteria

13. 2nd generation cephalosporins
Cefaclor
Cefuroxime axetil
Parenteral
Cefoxitin
Cefuroxime sodium

14. 2nd generation cephalosporins. Antibiotic coverage
Increased coverage against Gram negatives, while keeping coverage against Gram +.
Methicillin-sensitive Staphylococcus aureus
Streptococcus
Gram +
PEcK: Proteus, E. Coli, Klebsiella
Haemophilus influenzae, Neisseria Gonorrhoeae, Enterobacter.
Gram -

15. 3rd generation cephalosporins
Parenteral
Ceftriaxone
Cefotaxime
Ceftazidime

16. 3rd generation cephalosporins Coverage
Increased coverage against Gram negatives.
Decreased coverage against Gram +
Methicillin-sensitive Staphylococcus aureus (less active than 1st gen cephalosporins).
Streptococcus
Gram +
PEcK: Proteus, E. Coli, Klebsiella
Haemophilus,Neisseria, Enterobacter.
Serratia
Gram -

17. 3rd generation cephalosporins Clinical uses
Bacterial meningitis:
Gérmenes más frecuentes en adultos: S. Pneumoniae, N. meningitidis
Gonorrhea
Neisseria gonorrhoeae
Pneumonia: only in some cases
Only ceftazidime P. Aeruginosa infections.

18. Ceftriaxone and meningitis
Pharmacokinetics
Ceftiaxone crosses the Blood brain barrier and achieves good concentrations in CSF.
Antibacterial coverage
Active against Streptococcus y and Neisseria
S. Pneumoniae and N. meningitidis are responsible for 80% of meningitis cases in adults.

19. 4th generation cephalosporins
Parenteral
Cefepime

20. 4th generation cephalosporins Antibacterial coverage
Coverage against Gram + and Gram -, good activity against β-lactamase producing bacteria.
Methicillin-sensitive Staphylococcus aureus
Streptococcus
Gram +
PEcK: Proteus, E. Coli, Klebsiella
Haemophilus,Neisseria, Enterobacter.
Serratia
Acinetobacter
Pseudomonas aeruginosa
Gram -