To enjoy the presentation kindly download it. For Original view, download "Poetsen One" font style from dafont website. Here I have discussed all the first to fifth generation cephalosporins.

1. Beta Lactam
Antibiotics

2. CEPHALOSPORINS

3. These are a group of semisynthetic antibiotics
derived from 'cephalosporin-C obtained from
a fungus Cephalosporium.
They are chemically
related to penicillins; the nucleus consists of a
B-lactam ring fused to a dihydrothiazine ring,
(7-aminocephalosporanic acid).

4. By addition
of different side chains at position 7 of
B-lactam ring
(altering spectrum of activity)
and at position 3 of dihydrothiazine ring
(affecting pharmacokinetics),
a large number of
semisynthetic compounds have been produced.

5. Cephalosporins have been conventionaly
divided into 4 generations, and now
some
lately added members have been
designated
'5th generation'.
This division has a chronological
sequence of development, but more
importantly,
takes into consideration the overall
antibacterial spectrum as well as

6. All cephalosporins are bactericidal and have
the same mechanism of action as penicillin,
i.e. inhibition of bacterial cell wall synthesis.
However, they bind to different PBPs than
those which bind penicillins.
This may explain
differences in spectrum, potency and lack of
cross resistance.

7. Acquired resistance to cephalosporins could
have the same basis as for penicillins, i.e.:
(a) alteration in target proteins (PBPs) reducing
affinity for the antibiotic.
(b) impermeability to the antibiotic or its efflux
so that it does not reach its site of action.
(c) elaboration of B-lactamase which destroy
specific cephalosporins (cephalosporinases);
the most common mechanism.

8. Though the incidence is low, resistance has
been developed by some organisms, even against
the third generation compounds.
Individual cephalosporins differ in their:
• Antibacterial spectrum and relative potency
against specific organisms
• Susceptibility to B-lactamases elaborated by
different organisms.
•

9. Pharmacokinetic properties- many have to
be injected.
some are oral; majority are not
metabolized, and are excreted rapidly by the
kidney; have short t½s, probenecid inhibits
their tubular secretion.

10. Cephalosporins
First Gen.
Parenteral
Cefazolin
Oral
Cephalexin
Cefadroxil
Second Gen.
Parenteral
Cefuroxime
Cefoxitin*
Oral
Cefaclor
Cefuroxime axetil
Cef1rozil
Third Gen.
Parenteral
Cefotaxime
Ceftizoxime
Ceftriaxone
Ceftazidime
Oral
Celixime
Cefpodoxime proxetil
Cefdinir
Celtibuten
Fourth Gen.
Parenteral
Cefepime
Cefeirome
Fifth Gen.
Parenteral
Ceftaroline fosamil
Ceftobiprole
medocaril

11. FIRST GENERATION CEPHALOSPORlNS
These were developed in the 1960s, have high
activity against gram-positive but weaker against
gram-negative bacteria.

12. Cefazolin
It is the prototype first generation
cephalosporin that is active against most
PnG sensitive organisms,
i.e . Streptococci (pyogenes as well as viridans),
gonococci, meningococci, C. diphiheriae, H. influenzae,
clostridia and Actinomyces.
Activity against Klebsiella, Moraxella catarrhalis and
E. coli
is relatively high, but it is quite susceptible to
staphylococcal B-lactamase.

13. It can be given i.m.
(mildly painful) as well as i.v. and has a longer
t½ (2 hours) due to slower tubular secretion.
Cefazolin attains higher concentration in plasma
and in bile.
It is the preferred parenteral first
generation cephalosporin, especially for surgical
prophylaxis

14. SECOND GENERATION
CEPHALOSPORINS
These were developed subsequent to the first
generation compounds and are more active
against gram-negative organisms with wider
coverage, including some strains resistant to
first generation compounds.
Few members,
i.e. cefoxitin are active against anaerobes
as well, but none inhibits P. aeruginosa.

15. They are weaker than the first generation
compounds against gram positive bacteria.
Their utility has declined in favour of the
3rd generation agents.

16. Cefuroxime
It is resistant to gram-negative
B- lactamases, and has high activity against
organisms producing these enzymes including
PPNG and ampicillin-resistant H. influenzae,
while retaining significant activity on gram positive
cocci and certain anaerobes, but not
B. fragilis.

17. Cefuroxime can be injected i.m.,
and attains relatively higher CSF levels, but
has been superseded by 3rd generation
cephalosporins
in the treatment of meningitis.
It can
be employed for single dose i.m. therapy of
gonorrhoea due to PPNG.

18. THIRD GENERATION
CEPHALOSPORINS
These compounds introduced in the 1980s have
highly augmented activity against gram-negative
Enterobacteriaceae; and few members inhibit
Pseudomonas as well.
All are highly resistant
to B-lactamases from gram-negative bacteria.

19. However, they are less active on gram-positive
cocci and anaerobes.
Some members have good
blood-brain barrier penetrability and are useful
in meningitis.

20. Cefotaxime
It is the prototype of the third
génération cephalosporins; exerts potent action
on aerobic gram-negative as well as some gram
positive
bacteria, but is not active on anaerobes.
Prominent indications are meningitis
caused by gram-negative bacilli (attains relatively
high CSF levels), life-threatening resistant/
hospital-acquired infections, septicaemias and

21. It is an alternative to ceftriaxone for typhoid fever,
and can be utilized for single dose therapy
of PPNG urethritis, but is not
dependable for Pseudomonas infections.
Cefotaxime is deacetylated in the body;
the metabolite exerts weaker but synergistic
action with the parent drug.
The plasma t½
of cefotaxime is I hr, but is longer for the
deacetylated metabolite-permitting 12 hourly
doses in many situations.

22. FOURTH GENERATION
CEPHALOSPORINS
The distinctive feature of this newer subgroup of
cephalosporins is non-susceptibility to inducible
chromosomal lactamases produced by some
resistant bacteria alongwith high potency against
Entcrobacteriaceae and spectrum of activity
resembling the 3rd generation compounds.

23. Cefepime
Developed in 1990s, this 4th
generation cephalosporin has antibacterial
spectrum similar to that of 3rd generation
compounds,
but is highly resistant to B-lactamases,
Ps. aeruginosa, Strep. pneumoniae, H. influenzae and
aureus
are also inhibited but not MRSA.

24. Due to high
potency and extended spectrum, it is effective
in many serious infections like hospital-acquired
pneumonia, febrile neutropenia, bacteraemia,
septicaemia.
Higher concentrations are attained
in the CSF, and it is excreted by the kidney
with a t½ of 2 hours.

25. FIFTH GENERATION CEPHALOSPORINS
The recently developed members of this new
group are distinguished by their ability to kill
MRSA and some other bacteria which developed
penicillin resistance by producing altered PBPs.
Thus, these antibiotics are effective in many
resistant and hospital acquired infections.

26. They are also designated
'cephalosporins with anti- MRSA activity' .
Ceftaroline fosamil
It is a prodrug which after
i.v. infusion is rapidly converted by phosphatases
to the active ceftaroline that is cidal to many
gram + ive and gram - ive bacteria including
MRSA, penicillin resistant Strep. pneumoniae
and Enrerococcus faecallis, etc.

27. Ceftaroline owes
its activity to its ability to bind altered PBPs
expressed in these bacteria.
It has high affinity
for PBP2a (in MRSA), for PBP2b and PBP2x
It thus interferes with transpeptidation step of
bacterial cell wall synthesis and exerts lethal effect.
However, it is susceptible to extended-spectrum and
some
other B-lactamases so that organisms expressing

28. Adverse effects
Cephalosporins are generally well tolerated, but
are more toxic than penicillin.
I . Pain after i.m. injection
2. Diarrhoea
3. Hypersensitivity reactions
4. Nephrotoxicity
5. Bleeding
6. Neutropenia and thrombocytopenia
7. disulfiram-like interaction with alcohol

29. Uses
Currently cephalosporins are one of the most
commonly used antibiotics.
Among them they
cover a wide range of gram-positive and gram
negative bacteria including some anaerobes, but
not B. fragilis, mycobacteria and chlamydia.
Recently, some anti-MRSA cephalosporins have
been added to further extend their coverage.

30. 1. As alternatives to penicillins for ENT, upper
respiratory and cutaneous infections
2. Respiratory, urinary and soft tissue infections
caused by gram-negative organisms
3. Penicillinase producing staphylococcal
infections
4. Septicaemias
5. Surgical prophylaxis

31. 6. Meningitis
7. Gonorrhoea
8. Typhoid
9.Mix aerobic and anaerobic infection
10. Hospital Acquired Infection
11. Prophylaxis