‫ وحدة اليوزبكي‬.‫ د‬. ‫ م‬.‫أ‬
Head of Department of Pharmacology- College of
Medicine- University of Mosul-2014
Cephalosporins
3
Objectives
At end of this lecture, the students will be able to:
1- Identify the chemical structure and the classes of
cephalosporin.
2- Discuss the clinically important features of each
individual class of cephalosporin (Its pharmacokinetic
properties, antibacterial activities, clinical uses and side
effects).
3- Clarify the differences between different classes of
cephalosporin.
4- State other agents affecting the cell wall.
- At a level accepted to the quality assurance standards for
the College of Medicine/ University of Mosul.
Cephalosporin
- They are B-lactam antibiotics that are closely
related both structurally and functionally to the
penicillin.
- The chemical nucleus of the cephalosporin is 7amino cephalosporanic acid bears a close
resemblance to 6-amino penicillanic acid of
penicillin.
- Both penicillin and cephalosporin are safe during
pregnancy.
Cephalosporin Chemical structure
-The chemical nucleus of
the cephalosporin is 7amino cephalosporanic
acid.
- Most cephalosporin are
produced
semisynthetically
by
the
chemical attachment of
side chains to 7aminocephalospora-nic
acid.
Mechanism of action of cephalosporin
- Cephalosporin inhibit cell wall synthesis in a way
similar to that of penicillin.
- The cephalosporin are bactericidal drugs with
both gram positive and gram negative activity .
- They are more stable than penicillin to many
bacterial Beta Lactamases and therefore usually
have a broader spectrum of activity.
Classification of Cephalosporin
Cephalosporins have been classified as 1st, 2nd, 3rd , 4th or 5th generation on the basis of
bacterial susceptibility pattern & resistance to
B-lactimase:
1- First Generation:
Orally: Cefadroxil, Cephalaxin, Cephalothin.
Prenterally: Cefazolin.
2- Second Generation:
Prenterally: Cefoxitin, Cefotetan, Cefonicid,
Cefamandole.
Oral: Cefuroxime axetil, Cefprozil.
Classification of Cephalosporin
3- Third Generation :
Oral: Cefixime, Ceftibuten.
Prenterally: Cefotaxime, Ceftriaxone, Ceftizoxime,
Ceftazidime.
4- Forth Generation :
Cefepime is the most clinically useful. Must be
administered parenterally.
5- Fifth Generation:
Ceftobiprole : New drug.
First Generation Cephalosporin
Antibacterial Activity:
- These are highly effective against gram positive (G+) bacteria including strep., pneumococcus & staph.---(as penicillin
G).
- Also They have low activity against gram
negative organisms including: Proteus
mirabilis, E coli & Klebsiella pneumonia
(PEcK)
-
Clinical Uses of First Generation
Cephalosporin
- They are not used for serious systemic infection.
So used in:
- Oral : widely used for the treatment of RTI,
uncomplicated UTI & soft tissue infection
(cellulites) & soft tissue abscess (minor staph.
Infection).
- Prenterally: Cephazolin penetrate well into most
tissues mainly bone (not CNS). It is the drug of
choice for surgical prophylaxis & also for the
biliary tract & endocarditis.
Second Generation Cephalosporin
Antibacterial Activity:
- In general they are active against organisms
affected by first generation drugs (slightly less
activity against gram positive organisms).
- It has also activity against three additional Gnegative microorganism:
Haemophilus influenzae, some Enterobacter
aerogenes & some Neisseria species (in
addition to Proteus mirabilis, E coli & Klebsiella
pneumonia) (HEN PEcK).
Clinical Uses of Second Generation
Cephalosporin
Oral agents are used for :
1- The lower RTI such as sinusitis, otitis media &
acute
bronchitis
(against
B-lactimase
producing H.Influenzae).
2- Because Cefoxitin & Cefotetan, pocess activity
against anaerobic bacteroid, including bacteroid
fragilis, can be useful in the treatment of mixed
anaerobic
infection
(peritonitis
&
Diverticulitis).
3- Used for community acquired pneumonia.
Clinical Uses of Second Generation
Cephalosporin
Prenteral Agents:
- Used for the treatment of mixed anaerobic
infection such as abdominal & pelvic
infection as peritonitis.
3- Third Generation Cephalosporin
Antibacterial Activity:
- Their activity against gram positive organisms is
less than that of the first generation.
- They have greater activity against gram negative
bacteria than first or second generations plus
other enteric organisms & Serratia marcescens.
- Ceftazidime has activity against pseudomonas
aeroginosa.
Clinical Uses of Third Generation Cephalosporin
- They are used to treat serious infections caused
by organisms that are resistant to most other
drugs:
- Parenteral: Used for the treatment of: Brain
abscess, Meningitis, Gonorrhoea, Peritonitis,
Pneumonia, Surgical prophylaxis, Septicemia,
syphilis, Biliary tract infections, Skin infections.
- Oral Preparations: used for : Gonorrhoea, Otitis
media, pharyngitis, bronchitis and UTIs.
Forth Generation Cephalosporin
-Cefepime is the most clinically useful. Must
be administered parenterally.
- It has a wide antibacterial activity being
active against streptococci & staphylococci
(only those Methicillin susceptible).
- It is also effective against aerobic G-ve
organisms such as Enterobacter, E coli, K
pneumoniae, Proteus mirabilis &
pseudomonas aeroginosa.
Fifth Generation Cephalosporin
Ceftobiprole:
- New drug with activity against methicillinresistant Staphylococcus aureus, penicillinresistant Streptococcus pneumoniae and
Enterococci.
- Ceftobiprole cannot be given by mouth. Given
parentrally.
- Ceftobiprole is not licensed to be used in
children
- Ceftobiprole has been approved for use in Canada and Switzerland (after Feb 2008), and is
under review by regulatory authorities in the
United States, the European Union, Australia,
Russia and South Africa.
Side effects of Cephalosporin
1- Allergic Reactions of the penicillin type
such as rash, urticaria and anaphylaxis.
-There is cross allergy between penicillin
and cephalosporins involving about 10%
of patients.
2- Pain at the site of IM injection and
thrombophlebitis after IV use can occur.
3- All
cephalosporins
can
produce
pseudomembranous colitis caused by
Clostridium difficile.
4- If cephalosporins are continued for more
than 2 weeks , thrombocytopenia,
leucopenia,
interstitial
nephritis
or
abnormal liver function tests may occur
especially at high dosage. These reversed
on stopping the drug.
Other agents affecting the cell wall
1- Vancomycin:
Vancomycin is a tricyclic glycopeptide
that has become increasingly important
because of its effectiveness against
multiple drug resistant organisms such
as methicillin-resistant staphylococci.
Mechanism of action Vancomycin
Vancomycin inhibits synthesis of bacterial cell wall
phospholipids as well as peptidoglycan layer at a
site earlier than that inhibited by the B-lactam
antibiotics.
Antibacterial spectrum:
- In order to limit the increase in vancomycinresistant bacteria, it is important to restrict its use
to the treatment of serious infections caused by
B-lactam-resistant gram-positive microorganisms,
or for patients with gram-positive infections who
have a serious allergy to the B-lactams.
Clinical uses of Vancomycin
1-It is also used for potentially life-threatening
antibiotic-associated colitis due to Clostridium
difficile (pseudomembranous colitis) or
staphylococci.
2- Vancomycin is used in individuals with
prosthetic heart valves or in patients being
implanted with prosthetic devices.
3- Vancomycin acts synergistically with the
aminoglycosides and this combination can be
used in the treatment of enterococcal
endocarditis.
Side effects of Vancomycin
- Side effects are a serious problem with
vancomycin and include:
1- Fever, chills, and/or phlebitis at the infusion site.
2- Shock has occurred as a result of rapid
administration.
3- Flushing ("red man syndrome") and shock result due to histamine release caused by rapid
infusion.
4- Dose-related hearing loss has occurred in patients with renal failure who accumulate the
drug.
Other agents affecting the cell wall
2- Bacitracin:
- Bacitracin is a mixture of polypeptides that
inhibits bacterial cell wall synthesis.
- It is active against a wide variety of gram-positive organisms.
- Its use is restricted to topical application because of its potential for
nephrotoxicity.