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By the of this lecture the student will be able to:
Describe the mode of action of cephalosporins
Differentiate the spectrum of activity of the 4classes of cephalosporins
State the side effects & therapeutic uses of
cephalosporins
Describe the mechanism of action of vancomycin
Learning objective
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Cephalosporins
Closely related in structure to penicillin
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Cephalosporins:Mechanism of action
Cephalosporins inhibit the peptidoglycansynthesis of bacterial cell wall in a manner
similar to that of penicillin and are
considered bactericidal.
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Cephalosporins: Spectrum of Activity
All cephalosporins are active against most G+
cocci, including penicillinase-producing
staphylococci and many strains ofG- bacilli,
Relatively ineffective against enterococci.
Divided into 4 major groups called Generations
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Cephalosporins: Generations
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- First-generation cephalosporins
- Second-generation cephalosporins
- Third-generation cephalosporins
- Fouth-generation cephalosporinsIn general, 1st generation cephalosporins have better activity
against gram-positive bacteria and less gram-negative activity,
while 3rd generation agents, with a few exceptions, have better
gram-negative activity and less gram-positive activity. The fourthgeneration agent has both gram-positive and gram-negative
activity.
Elimination is primarily via the kidneys, though a few exceptions
include ceftriaxone which have significant biliary elimination
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Examples: Cefazolin
- They have a stronger antimicrobial action on G+
bacteria than that of the other generations.
- Their action on G- bacteria is relatively poor.
- They have nephrotoxicity to a certain degree.
- They are NOT effective against pseudomonas.
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First Generation Cephalosporins
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- Comparatively, they are stable for beta- lactamase
(penicillinase ).
-They are chiefly used in treating infection of thepenicillinase-productive aurococcus (S.aureus) and
surgical prophylaxis.
- Do not penetrate the central nervous system andcan not be used to treat meningitis.
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First Generation Cephalosporins
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Second Generation Cephalosporins
Examples: cefaclor
Action of this generation on G+ bacteria is the
same or less than that of the first generation. Their antimicrobial action on G- bacteria is
increased
Some of them are effective against anaerobes
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Second Generation Cephalosporins
- Ineffective againstp.aeruginosa. They are stable to many kinds of beta-
lactamases. Do not penetrate the central nervous system
and can not be used to treat meningitis
- less nephrotoxic than the first generation.
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Third Generation Cephalosporins
Ceftriaxone
One of the broadest spectrum cephalosporins
high activity against G- bacteria.
low activity against G+ bacteria.
The highest resistance to -lactamase.
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Third Generation Cephalosporins
The best penetration into the CSF
Almost no nephrotoxicity
Some of them are effective against
P.aeruginosa and enteric bacilli
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Fourth Generation Cephalosporins
e.g Cefepime:
Similar to third generation agents but more
resistant to hydrolysis by beta lactamase.
It is useful against many enterobacter resistantto other cephalosporins.
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Cephalosporins:Side effects
Relatively few and low
The most common ones are Allergy-
hypersensitivity reactions (5%-10%)anaphylaxis, fever, skin rashes, nephritis,
granulocytopenia, and hemolytic anemia.
During treatment with third and fourth generation
drugs, resistant bacteria, as well as fungi, often
proliferate and may inducesuperinfections.
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Cephalosporins:Side effects
Nephrotoxicity:
The first-generation cephalosporins have certain
nephrotoxicity.
The second-generation have slightnephrotoxicity.
The third and fourth generation have nonephrotoxicity.
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Clinical uses of cephalosporins
1. Infections resistant to penicillins
2. Patients sensitive to penicillins
3. Gram-ve urinary tract infections andmeningitis
4. Respiratory tract infections
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Cephalosporins
NB:
Patients with history ofpenicillin allergy may
tolerate cephalosporins.
But patients with history ofanaphylaxis
shouldneverreceive cephalosporins
Non of the cephalosporins is active against
MRSA.
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Other inhibitors of cell wall
synthesis
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Vancomycin
It is active only against gram-positive bacteria
especially staphylococci.
Vancomycin inhibits synthesis of bacterial cell
wall phospholipids as well as peptidoglycan
polymerization .
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Vancomycin: Therapeutic indications
1. Infections caused by methicillin resistant
staphylococci (MRSA)
2. Vancomycin is used in combination with:a) gentamycin for treatment of enterococcal
endocarditis in penicillin allergic patient.
b) 3rd generation cephalosporins fortreatment of meningitis caused by penicillin
resistant pneumococci.
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1. Irritation leading to phetibitis at the site of
infection.
2. Chills and fever.
3. Ototoxicity and nephrotoxicity especially if
given with another ototoxic or nephrotoxic
drug as aminoglylosides.
4. Histamine release . (red man syndrome)
Vancomycin: Adverse effects
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