1. Cell wall inhibitor Cephalosporins Dr. Naza M. Ali Lec 5 13-12-2016 D

2. Cephalosporins
The cephalosporins are beta-lactam antibiotics that are closely related both structurally & functionally to penicillins.
Are produced semisynthetically by the chemical attachment of side chains to 7-aminocephalosporanic acid.

3. Mechanism of action and resistance
Bind to PBPs on bacterial cell membrane to inhibit bacterial cell wall synthesis.
Structural differences from penicillins render cephalosporin less susceptible to penicillinase produced by staphlococci, but many bacteria are resistance through the production of other beta-lactamase that can inactivate cephalosporins.
Resistance also from decreased in membrane permeability to cephalosporins and from changes in PBPs.
Methicillin-resistant staphylococci are also resistant to cephalosporin.

4. 1.First-generation drug
Antibacterial spectrum
1.First-generation drug
Cefazolin ( parenteral) ,
Cephalexin and Cefadroxil (oral)
active against +gm cocci (staphylococci, streptococci)
Proteus, E.coli , K pneumoniae (PEck)
Used in surgical prophylaxis in selected condition.

5. 2.Second generation:
have greater activity against three additional gram-negative
H. influenzae, Enterobacter aerogenes, Neisseria
whereas activity against gram-positive is weaker HENPEcK
Cefoxitin, Cefotetan active against Bacteroides Fragilis / IV
Cefuroxime in community acquire pneumonia / oral
Cefaclor in otitis, lower RTI , sinusitis / oral
Cefamandole active against H. influenza

6. 3.Third generation:
have enhanced activity against gram-negative bacilli and some are able to cross BBB
Ceftriaxone or Cefotaxime drug of choice in meningitis and for empiric therapy
Ceftriaxone , Cefixime drug of choice in gonorrhea
Ceftazidime, Cefoperazone activity against P.aeruginosa
Cefpodoxime, Cefdinir are orally

7. 4.Fourth generation:
Cefepime
parenterally has a wide antibacterial spectrum.
Combine gram positive activity of 1st generation with
wider gram negative spectrum of 3rd generation.
( Enterobacter, E. coli, K. pneumoniae,
Proteus mirabilis, P. aeruginosa).

8. 5. Fifth generation: Ceftobiprole Ceftaroline A new cephalosporin with activity against Methicillin-Resistant Staphylococcus (MRSA)

9. 1st Spectrum Name of drugs treatment Gm+ cocci, PEck Cefazolin / Inj
Generation
Spectrum
Name of drugs
treatment
1st
Gm+ cocci,
PEck
Cefazolin / Inj
Cephalexin /oral
Cefdroxil / oral
surgical prophylaxis,
penetration to bone
pharyngitis
2nd
HENPEcK
Bacteroides fragilis
Cefoxitin /inj Cefotetan / inj
Cefuroxime oral
Cefaclor /oral
community acquire
Pneumonia
Otitis, lower RTI, sinusitis
3rd
gram-negative bacilli
some are able to cross BBB
Ceftriaxone /inj Cefotaxime /inj
Ceftriaxone/ inj
Cefixime /oral
Meningitis
Gonorrhea
P. aeruginosa
Ceftazidime/ inj
Cefoperazone/inj
Cefpodoxime/oral
Cefdinir/ oral

10. 4 th Spectrum Name of drug Disease wide antibacterial .
Generation
Spectrum
Name of drug
Disease
4 th
wide antibacterial .
Combine gram positive 1st with wider gram negative 3rd Enterobacter,
E. coli,
K. pneumoniae,
Proteus mirabilis,
P. aerugin,
Cefepime parenteral
5th
MRSA Enterobacter,
Gm-ve rods
Ceftobiprole,
Ceftaroline:

11. Pharmacokinetics Administration: IV , IM or oral
Distribution: cross the placenta
Fate: tubular secretion and GF
(Ceftriaxone is excreted through the bile into the feces)

13. Adverse effects:
Allergic manifestations
Patients who have had an anaphylactic response, Stevens-Johnson syndrome to penicillins should not receive cephalosporins.
Should be avoided or used with caution in individuals who are allergic to penicillins ( 8-10% show cross- sensitivity).
Cephalosporin that contain methylthiotetrazole group: Cefamandole, cefotetan, cefoperazone cause hypoprothrombinemia and bleeding disorders.

14. Other Beta-Lactam Antibiotics
Dr. Naza M Ali Lec

15. Other beta-Lactam Antibiotics
A. Carbapenems B. Monobactam C. Beta-Lactamase inhibitors

16. A. Carbapenems
Chemically different from penicillins but retaining the beta-lactam ring structure.
Imipenem, meropenem, ertapenem , doripenem
Have wide activity against gram positive cocci, gram negative rods, anaerobes.
Plays a role in empiric therapy because it is active against
penicillinase-producing gram-positive and gram- negative organism, anaerobes, P. aeruginosa
Used in combination with aminoglycoside for pseudomonal infection

17. They are used parenterally & are useful for infections
caused by organism resistant to other antibiotics.
They are drugs of choice for infections caused by
Enterobacter.
Imipenem is compounded with cilastatin to protect it
from metabolism by renal dehydropeptidase.
Imipenem & meropenem are administered IV and
penetrate well into body tissues & fluids, including CSF
when meninges are inflamed.

18. B. Monobactam Drugs with monocyclic beta-lactam ring.
Aztreonam is resistant to action of beta -lactamases.
has antimicrobial activity against gram-negative rods (Enterobacteriaceae) including pseudomonas
It lacks activity against gram-positive organisms and anaerobes.
It is administered (IV or IM), is excreted in urine, it can accumulate in patients with renal failure.
Aztreonam is relatively nontoxic, can use as alternative for treating patients who are allergic to penicillins or cephalosporins.

20. C. Beta-Lactamase Inhibitors
Hydrolysis of the beta-lactam ring by enzymatic cleavage or by acid, destroys the antimicrobial activity.
Clavulanic acid, Sulbactum, Tazobactam contain a
beta-lactam ring but, by themselves, do not have
significant antibacterial activity.
They bind to and inactivate beta-lactamases protecting the antibiotics that are substrates for these enzymes.
clavulanic acid and amoxicillin combination.

22. contain bete lactam ring Gm+ cocci gm- rods (enterobacteriaceae)
Carbapenem:
Imipenem,
Meropenem
Ertapenem
differ in str
contain bete lactam ring
Gm+ cocci
gm- rods (enterobacteriaceae)
anaerobes
pseudomonas +aminoglycosid
Parenterally
Monobactam:
Aztreonam
Monocyclic beta lactam ring
narrow spec.
-ve rode
P. aeruginosa
No activity for +ve
No toxic,safe
IM,IV
Beta-lactam inhibitors:
Clavulanic acid,
Sulbactam,
tazobactam
Contain beta lactum ring,
do not have significant antibacterial activity
Oral,
parenteral