1. Cephalosporins
Four Generations!
Bactericidal & Time-Dependent!

2. Cephalosporins A B-lactam Analogous to PCN in
Binding to specific PCN-binding proteins
Inhibition of cell wall synthesis by blocking the transpeptidase step of peptidoglycan
Bactericidal & Time-Dependent!

3. Cephalosporins Tissue Penetration: very good
Lung, kidney, muscle, synovial, pericardial, peritoneal and pleural fluids
5-10% cross reactivity rate with PCN allergies
Specific resistance rates differ widely based on chemical structure (see cross reactivity article)
Side Effects
GI: 2-5%
Rash: 1-3%
Neutropenia: <1%
Seizures: <1%
 Lactam antibiotics
MOA: binds to PBP-inhibit bacterial cell wall synthesis
Most agents are renally excreted
Exception: Ceftriaxone

4. Spectrum Activity
In general a  in gram + and an  in gram - activity are observed as you move through generations 1-3.
Cefepime (4th generation) maintains an excellent
gram + and - activity.

5. 1st Generation Cephalosporins
Cefazolin, Cefaclor (PO), Cephalexin (PO), Cefadroxil (PO)
GRAM +
>60%: Strep Pneumo, Strep ABCG, Strep viridans, MSSA
30-60%: Staph epidermidis
Moderate GRAM - coverage
>60%: Proteus, E. Coli, Klebsiella Salmonella, Shigella, Neisseria gonorrheae, H. Influenzae

6. 2nd Generation Cephalosporins
Cefuroxime (IV, PO), Cefotetan, Cefoxitin
GRAM +
>60%: Strep: Pneumo, Viridans, MSSA
30-60%: Staph epidermidis
 Gram - coverage vs. 1st gen
>60%: Proteus, E. Coli, Klebsiella, Moraxella, Neisseria gonorrheae, H. Influenzae, Serratia.
30-60%: Citrobacter, Enterobacter.
Cefotetan/Cefoxitin:  anaerobic coverage
>60%: Clostridium (not difficile), B. fragilis

7. 3rd Generation Cephalosporins
IV: Ceftriaxone, Ceftazidime, Cefotaxime PO: Cefpodoxime, Cefixime, Cefdinir, Ceftobiprole
Gram +: same as 1st & 2nd ( bit less with Ceftaz)
Good activity against Streptococci!
Less activity against Staph than 1st and 2nd generation.
 Gram - coverage vs. 2nd gen
>60%: Proteus, E. Coli, Klebsiella, Moraxella, H. Influenzae, Serratia, Citrobacter, Enterobacter, Salmonella, Shigella, Pseudomonas (Ceftaz)
30-60%: Neisseria gonorrheae (best with Ceftriaxone).

8. 4th Generation Cephs: Cefepime
Very broad coverage of both Gram + and Gram -
Like 3rd generations, but:
Very good against all strains of neisseria (>60%)
Better vs. acinetobacter (30-60%)
Not active against anaerobes

9. Carbapenems Imipenem, Meropenem, Ertapenem, Doripenem
Bactericidal-Time dependent

10. Carbapenems Imipenem, Meropenem, Ertapenem, Doripenem
Beta-lactams, but have somewhat different chemical structure vs. PCNs and CEPHs
MOA: cause lysis of bacterial cell wall
Highly stable to beta-lactamases!!
Only available in IV form
Have PAE against Gram - bugs
Tissue penetration: good
Renally eliminated (require adjustment)

11. Carbapenems Imipenem, Meropenem, Ertapenem, Doripenem
Side Effects
GI: 4-5%
Rash: 2-3%
Infusion related: 3%
Seizures: ~1%
Bind to GABA
Ertapenem:
 infusion rxns (7-10%)
CNS: confusion etc 5-10%)
Coverage
VERY BROAD SPECTRUM
Gram + (NOT MRSA)
Gram – (including pseudomonas)
Anaerobes

12. Monobactams: Aztreonam
Also a beta lactam
MOA: inhibits bacterial cell wall synthesis
Coverage: Gram – only
Covers Pseudomonas
Not used as often as other agents
Well tolerated
Bactericidal-Time dependent!

13. Gycopeptide-Vancomycin
Bactericidal-Time dependent killer

14. Gycopeptides Vancomycin
MOA: Inhibit bacterial cell wall synthesis by binding to the D-ala-D- ala terminus of the pentapeptide, sterically interfering in the elongation of the cell wall polymer.
Toxicities:
Ototoxicity <1%
Renal Dysfunction <1%
Want trough levels ~ mg / dL
Poor oral bioavailability
Side Effects: Red man syndrome
Facial flushing and hypotension
Histamine reaction related to rate of infusion
Always infuse Vancomycin over ≥ 60 min

15. Gycopeptides Vancomycin
ONLY COVERS GRAM +
Treatment of choice for MRSA currently or
Serious Gram + infection in PCN allergic patients.

16. How does resistance to Vancomycin develop?
Primarily through plasmid-mediated changes in permeability to the drug, and  binding of vancomycin to receptor molecules.
Widespread use leading to resistance
VRE: Vancomycin resistant enterococci
Linezolid (Zyvox)