2. Cephalosporins are semi synthetic beta lactam
antibiotics closely related both structurally and
functionally to penicillins. They have an
advantage over the penicillins in that they are
less susceptible to inactivation by beta lactamase
enzyme and have a broader spectrum of activity.
Hence are often used when penicillin treatment
has proved ineffective.
3. mechanism of action of cephalosporins
Initially derived from the fungus Cephalosporium
sp., cephalosporins are a large group of
bactericidal antimicrobials that work via their
beta-lactam rings. The beta-lactam rings bind to
the penicillin-binding protein and inhibit its
normal activity
Mode of action of cephalosporins
Cephalosporins are bactericidal in action and
inhibit the synthesis of the
bacterial cell wall.
4. Classification of cephalosporins.
Cephalosporins are classified into
generations basing on bacterial
susceptibility patterns and resistance to
beta lactamases, as follows:-
7. First generation cephalosporins are
mainly active against gram positive
bacteria and have limited activity
against gram negative bacteria like
H.
influenzae.
8. Second generation cephalosporins
This group includes:-
Cefuroxime ,Cefaclor.
Second generation cephalosporins have similar coverage against
gram positive organisms as the first generation but with enhanced
gram negative coverage. However, they are less active against gram
+ve bacteria than the first generation and have no activity against
enterococci or P. aeruginosa.
9. Third generation cephalosporins
This class includes:-
Ceftriaxone Cefotaxime Ceftazidime Cefixime'
Cefpodoxime Cefdinir
Third generation cephalosporins are less active than the
first and second generation drugs agaim'tgram +ve
bacteria, but are more active against gram -YJvbacteria.
including those resistant to the first and second
generation. They are less active against S. aureus than the
first generation drug.
-
10. Fourth generation cephalosporins I •
These drugs include; Cefepime.
Fourth generation drugs, like the third generation,
have an extended spectrum of activity against gram
-ve bacteria compared to the 15t and 2nd
generation. Cefepime is active against gram positive
and gram negative infections including Pseudomonas
aeruginosa.
11. CEPHALEXIN
1st generation.
Available preparations: Capsules 2S0mg, SOOmg Powder for
oral suspension 12Smg/ 5ml, 250mg/5ml.
Pharmacokinetics
Cephalexin is absorbed rapidly from the GIT after oral
administration,
distributed widely into most body tissues including the
gall bladder, sputum, bone, synovial fluid. It is not
metabolized.
excreted in unchanged in urine.
12. mechanism of action of cephalexin
Cephalexin inhibits bacterial cell wall synthesis, leading
breakdown and eventualy cell death. Well absorbed from
the upper gastrointestinal tract with nearly 100% oral
bioavailability. Cephalexin is not absorbed in the stomach
but is absorbed in the upper intestine.
Mode of action Cefalexin
It works by killing the bacteria that causes the infection.
Cefalexin can treat a wide range of bacteria so it works well
for a variety of infections, such as chest, skin or urinary
tract infections (UTIs).
13. Indications
Otitis media Impetigo Cellulitis Osteomyelitis
Urinary tract infections
Dental infections Bronchitis Prevention of
bacterial endocarditis Pneumonia
Erysipelas Pyomyositis Septic arthritis, Pharyngitis
,Tonsillitis.
Contraindications
known allergy to cephalosporins
15. Drug interactions
Probenecid decreases renal excretion of
cephalexin, increasing its blood levels.
Oral contraceptives effectiveness may
be reduced by cephalexin
Aminoglycosides and loop diuretics may
increase the nephrotoxicity caused by
cephalexin.
17. Mechanism of action Cefuroxime
Cefuroxime is a bactericidal agent that acts by inhibition
of bacterial cell wall synthesis. Cefuroxime has activity
in the presence of some beta-lactamases, both
penicillinases and cephalosporinases, of Gram-negative
and Gram-positive bacteria.
Mode of action Cefuroxime,
like the penicillins, is a beta-lactam antibiotic. By binding
to specific penicillin-binding proteins (PBPs) located inside
the bacterial cell wall, it inhibits the third and last stage
of bacterial cell wall synthesis.
18. Pharmacoldnetics
Cefuroxime axetil is absorbed from the GIT and its
absorption is enhanced by food.
It penetrates well into most fluid spaces and tissues
It is not metabolized and is excreted primarily in
urine.
Indications ; Acute and chronic bronchitis Acute
otitis media , Sinusitis , Tonsillitis, Pharyngitis
,Impetigo, pyoderma, Pneumonia, Gonorrhoea ,
Bacterial Meningitis Surgical prophylaxis, Pelvic
inflammatory disease
19. Contraindications known allergy to cephalosporins
Drug interactions
Efficacy of oral contraceptives may be reduced.
Nephrotoxic drugs such as gentamycin, vancomycin may
increase the potential for nephrotoxicity.
Probenecid inhibits the tubular secretion of cefuroxime
resulting into prolonged high serum concentrations
A disulfiram-like reaction may occur when alcohol is given
concurrently with cefuroxime
20. Side effects
Skin rash, Headache Urticaria ,Fever Nausea and
vomiting Anorexia Diarrhoea Abdominal pain
Vaginal candidiasis
21. Key issues to note
Cefuroxime axetil is well absorbed after a light meal,
therefore
it should be administered with food
Shake suspension well before use.
The tablet should not be broken before swallowing
Reconstituted injectable solution is stable for, 24 hours at
room temperature and 48hours when refrigerated
Reconstituted oral suspension may be stored at room
temperature or refrigerator and discarded after 10 days
22. CEFTRIAXONE
3rd generation
Available preparations: Powder for Injection 1M / IV
SOOmg, I g, 2g
Pharmacokinetics
Ceftriaxone is widely distributed into body tissues and
fluids after parenteral administration. It penetrates well
into the CSF, especially when the meninges are inflamed
and it's excreted unchanged in urine.
23. Mechanism of action ceftriaxione
Ceftriaxone works by inhibiting the mucopeptide
synthesis in the bacterial cell wall.
Mode of action.
The beta-lactam moiety of ceftriaxone binds to
carboxypeptidases, endopeptidases, and
transpeptidases in the bacterial cytoplasmic
membrane. These enzymes are involved in cell-
wall synthesis and cell division.
25. Drug intractions
Ceftriaxone may reduce the
effectiveness of oral contraceptives
Concomitant use with aminoglycosides
produces synergistic antimicrobial
activity against Pseudomonas aeruginosa
and some strains of Enterobacteriaceae
26. CEFEPIME
Available preparations : Powder for injection Ig, 2g
Pharmacokinetics .,
Cefepime is rapidly and almost completely absorbed
following Intramuscular injection. It is widely distributed
in body tissues and fluid and is excreted unchanged in
urine.
Indications
Urinary tract infection Skin and skin structure infection.
Nosocomial pneumonia Surgical prophylaxis Intra
abdominal infections Febrile neutropenia
27. Mechanism of action of Cefepime
IT inhibits bacterial cell wall synthesis by
covalently binding enzymes responsible for the
final step in transpeptidation during
peptidoglycan wall synthesis.
Mode of action.
Binds to cell wall causing defects in the cell wall
leading to autolysis and subsequent death of the
organism.
28. Contraindications
History of anaphylactic reaction to penicillins
Known hypersensitivity to cephalosporins
Side effects
Skin Rashes ,Thrombophlebitis ,Fever Vaginal
candidiasis, Anaphylaxis Headache Vomiting
Diarrhea ,Pseudomembranous colitis Abdominal
pain ,Pain at injection site.
29. Drug interactions
Aminoglycosides and frusemide may increase the
risk of nephrotoxicity and ototoxicity with cefepime
, Probenecid decreases renal excretion of cefepime
Key points to note
Store the drug at room temperature and protect
from light
Cefepime is incompatible with metronidazole,
aminoglycoside and aminophylline
