antibiotic 2nd year module

8/3/2019 Antibiotic 2nd Year Module

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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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antibiotic 2nd year module

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