Cephalosporins are a group of antibiotics derived from the fungus Cephalosporium. The first cephalosporin was discovered in 1948. They have a bicyclic molecular structure containing a beta-lactam ring. Cephalosporins are classified into generations based on their spectrum of activity, with later generations having broader spectra. They work by inhibiting bacterial cell wall synthesis. Common indications include UTIs, respiratory infections, and surgical prophylaxis. Side effects include allergic reactions and nephrotoxicity. Resistance can develop through beta-lactamase production or alterations in penicillin-binding proteins. Cephalosporins are commonly used oral and parenteral antibiotics with broad spectrums
4. Any of a group of widely used broad-spectrum
antibiotics, originally isolated as a product of
fermentation from the fungus Cephalosporium
acremonium are called Cephalosporins.
Definition
Cephalosporium acremoniumFig:
5. The first chemical compounds of
the cephalosporin group were
isolated from Cephalosporium
acremonium, a cephalosporin-
producing fungus, first discovered
by Giuseppe Brotzu in 1948.
The Cephalosporines are isolated from
Cephalosporium species
Prepared semisynthetically
Giuseppe Brotzu
(1895-1976) Italy.
History:
6. It has a bicyclic system containing 4-
membered 𝜷 -lactam ring fused to a six
membered dihydrothiazine ring system
.Nucleous of the most cephalosporin is 7-
amino-cephalosporanic acid (7-ACA) .
Possible modifications
•7-Acylamino side chain
•3-Acetoxymethyl side chain
•Substitution at C-7
Chemistry of Cephalosporin:
N
O
HHH
N
O
S
CO2H
O
C
Me
O
H2N
CO2H
7
H
6
1
2
3
4
58
N
O
HH
H2N S
CO2H
O
C
Me
O
7-Aminocephalosporinic acid
(7-ACA)
Dihydrothiazine
ring
b-Lactam
ring
7. Properties of cephalosporins
Broad spectrum activity
They are water soluble
The molecular weight of cephalosporins is 400-450
Relatively stable to pH and temperature changes
Nucleus of cephalosporin is 7-amino cephalos
poranic acid
Their activity is not reduced by serum
8. Range from very narrow spectrum to very
broad spectrum
nucleus Consists of dihydrothiazine ring
fused to a β–lactam ring
7-aminocephalosporanic acid has been
modified by addition of different side chains
to create a whole family of cephalosporin
antibiotics.
9. Classification of cephalosporins:
According to generations Cephalosporins
are following types…
First Generation
Second Generation
Third Generation
Fourth Generation
Fifth Generation
Sixth Generation
13. Exhibit somewhat increased activity against
gram negative organisms,
but much less active than third generation
agents.
Less active against gram positive cocci & bacilli
compared to first gen. drugs.
15. Highly augmented activity against gram-negative
organisms
All are highly resistant to β-lactamases from
gram negative bacteria.
Some members of this group have enhanced ability
to cross the blood-brain barrier eg. Ceftriaxone .
17. Highly active against G –ve organisms
Effective against bacterial infections
resistant to earlier drugs.
18. Ceftobiprole
Ceftaroline
Active against, g +ve cocci especially MRSA
penicillin resistant S. pneumoniae
and enterococci
Fifth Generation:
19. Pharmacokinetics:
Rout of administration:
Oral
Parenteral
Distribution
Body fluid
Joint fluid
Pleural fluid
CNS
Elimination
Unchanged in urine
Renal tubules
Plasma Half-life: 1-4 hours mostly
20. Peptidoglycan layer is important for cell wall structure integrity of
bacteria .
The final step in synthesis of peptidoglycan ( Transpeptidation) is
facilitated by transpeptidase ( PBP- Penicillin Binding Protein )
Cephalosporin comptitively inhibit PBP as it mimics the structure of
D-Ala-D-Ala link to which PBP bind for cross-linking of peptidoglycan
.
As it disrupting the cross-linking process the cell wall will lose
its strength which results in cell lysis.
Mechanism of action:
23. By Flow Chart:
Cephalosporin
Act as transpeptidase enzyme
Inhibit transpeptidation reaction
Block peptidoglycine synthesis
Activation of Autolytic enzyme
Increase the permeability of cell membrane
Cell explodes and lysed
Death of microorganism
24. oUTI
oInfection of gut
oRespiratory tract infection
oBoils, abscess
oProphylaxis in surgery
oBiliary sepsis
oPerson allergic to penicillin
Indication..
29. Nephrotoxicity:
Interstitial Nephritis
Renal Tubular necrosis
Others:
Disulfiram-like reaction
Local irritation after I/M injection
Thromboflavitis after repeated I/V
Bleeding tendency
Eosinophilia and thrombocytosis
Defect of newborn babies
Pharyngitis ( Throat infection)
Stillbirth or Miscarriage
30. Impermeability to the antibiotic.
-to reach its site of action
Alteration in PBPs -antibiotics bind with low
affinity
Elaboration of β-lactamases; that can
hydrolyze the β-lactam ring and inactivate the
cephalosporin (most prevalent mech)
Resistance
31. Similarity :
Both obtained from fungus
Structural similarity
Mechanism action ( Cell wall inhibitor )
Dissimilarity :
Resistant to beta lactamase
Antibiotic spectrum
Precursor
COMPARISON WITH PENICILLIN
32. Broad spectrum of activity
Stability to Beta-lactamase
Oral and parenteral preparations
Widely accepted
Treats ‘Day to Day’ as well as serious infections.
High safety profile.
Why Cephalosporin is used-
33. Extremely widely used :-
Safe :
Side effects specific to individual members of
the family as well as the family as a whole
Not necessarily cross reaction with penicillin
hypersensitivity