CEPHALOSPORINS

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CEPHALOSPORINS
roselynnaranjo
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Cephalosporins

• are B-Lactam antibiotics isolated from
  Cephalosporium spp.

• inhibit wide variety of gram() and gram(-)
  bacteria

• Abraham and Newton, the suppliers of fungi
  cultures
• isolated three principal antibiotic components
• Cephalosporin PI
• Cephalosporin N
• Cephalosporin C

- a steroid with minimal antibacterial property
- Identical with synnematin N ( also called
penicillin N

• Resistant to S. aureus B-lactamase antibacterial
  
• property is inferior to penicillin N.

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Cephalosporins

• Cephalosporin N or Penicillin N
• - the amino acid in the chain confers more
  activity against
• gram(-) bacteria particularly
  Salmonella spp.
• - less active against gram() organism
  -
  contains thiazolidine ring

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Cephalosporins

• Cephalosporin C
• - congener of Penicillin N
• - contains dihydrothiazide ring

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Nomenclature of Cephalosporins

• Chemical Abstracts
• gt fused ring is named 5-thia, 1-azabicyclo4.2.0
  oct-2-ene
• gt CEPHALOTHIN (is an antibiotic of the
  cephalosporin class. It is related to the
  penicillin drugs in how it kills bacteria, but
  cephalosporins have a much broader range of
  activity against bacteria than penicillins. is
  3-(acetoxymethyl)-7-2-(thienylacetyl)amino-8-oxo
  -5-thia-1-azabicyclo4.2.0oct-2-ene-2-carboxylic
  acid.
• gt saturated bicyclic ring system is named as
  cepham
• gt all cephalosporins and cefamycins are named as
  3-cephems, to designate the position of the
  double bond in the structure.

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Degradation of Cephalosporins
S O L V O L Y S I S
solvolysis
(Strong acidic solution)
Desacetylcephalosporin
Cephalosporin
Lactonize
Desacetylcephalosporin Lactone ( In active form)
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Degradation of Cephalosporins
H Y D R O L Y S I S O F B L A C T A M A S E
Hydrolysis of the ß-lactamase
Cephalosporin
Cephalosporoic acid
Anhydrodesacetylphalosporoic acid
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Degradation of Cephalosporins
A C Y L A S E S
Cephalosporin
Aminocephalosporanic acid
Desactyl-7- Aminocephalosporanic acid
Lactone
CEPHALOSPORIN STRUCTURE
increases the acid stability of the beta-lactam
ring.
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Spectrum of Activity
CEPHALOSPORINS
gt are considered broad-spectrum
antibiotics with similar
activities to that of ampicillin. gt more
resistant to the inactivation by the
beta-lactamases,
particularly those produced by gram()
bacteria. gt exhibit potent activity against
most species of Klebsiella
Different potencies are due to
1. Different bacterial strains
2. Characteristics of individual bacterial species
3. Resistance to the inactivation of the
beta-lactamases
4. Permeability of the bacterial cell
5. Intrinsic activity against bacterial enzymes
involved in cell wall synthesis and cross
linking.
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Antipseudomonal Cephalosporins
Moxalactam
contain the polar functionalities such as
(carboxy and N-acylureido)
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Adverse Reactions and Drug Interactions
gt non-toxic compound and exhibit selective
toxicity towards bacteria
gt Allergy and hypersensitivity are most common
reactions

• cefamandole, cefotetan, cefmetazole, moxalactam,
  cefoperazone have
• higher incidence of hypoprothrombinemia

gtpoor nutritional status, debilitation, GIT
surgery, hepatic disease or renal failure may
lead to severe bleeding
gtvitamin K supplement is given to high risk
patients undergoing cephalosporin therapy
gtreact with alcohol due to the accumulation of
acetaldehyde
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Classification of Cephalosporin
1. First generation Cephalosporins

• are moderate spectrum agents, with a spectrum of
  activity or treatable range of bacteria that
  includes penicillinase-producing,
  methicillin-susceptible staphylococci and
  streptococci
• They also have activity against some Escherichia
• coli, Klebsiella pneumoniae and Proteus
  mirabilis,
• but have no activity against Bacteroides
  fragilis, enterococci, methicillin-resistant
  staphylococci, Pseudomonas, Acinetobacter,
  Enterobacter, indole-positive Proteus, or
  Serratia.

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Classification of Cephalosporin
1. First generation Cephalosporins
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Classification of Cephalosporin
2. Second generation Cephalosporins
gt have a greater Gram-negative spectrum while
retaining some activity against Gram-positive
cocci. They are also more resistant to
beta-lactamase.
Cefaclor (Ceclor, Distaclor, Keflor, Raniclor)
Cefonicid (Monocid) Cefprozil (cefproxil
Cefzil) Cefuroxime (Zinnat, Zinacef, Ceftin,
Biofuroksym) Cefuzonam
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Classification of Cephalosporin
2. Second generation Cephalosporins
gt with antianaerobe activity
Cefmetazole Cefoxitin Cefotetan

gt The following cephems are also sometimes
grouped with second-generation cephalosporins
A. Carbacephems -
loracarbef (Lorabid) B. Cephamycins
- cefbuperazone, cefmetazole
(Zefazone), cefminox,
cefotetan (Cefotan),
cefoxitin (Mefoxin)
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Classification of Cephalosporin
3. Third generation Cephalosporins

• Third-generation cephalosporins have a broad
  spectrum of
• activity and further increased activity
  against Gram-negative
• organisms.
• They may be particularly useful in treating
  hospital-acquired
• infections, although increasing levels of
  extended-spectrum
• beta-lactamases are reducing the clinical
  utility of this class of
• antibiotics.
• They are also able to penetrate the CNS, making
  them useful
• against meningitis caused by pneumococci,
  meningococci, H.
• influenzae, and susceptible E. coli,
  Klebsiella, and penicillin-
• resistant N. gonorrhoeae.

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Classification of Cephalosporin
3. Third generation Cephalosporins
Cefixime (Suprax) Cefmenoxime Cefodizime
Cefotaxime (Claforan) Cefpimizole
Cefcapene Cefdaloxime Cefdinir (Omnicef,
Cefdiel) Cefditoren Cefetamet
Cefpodoxime (Vantin,) Cefteram Ceftibuten
(Cedax) Ceftiofur
Ceftiolene Ceftizoxime (Cefizox) Ceftriaxone
(Rocephin)
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Classification of Cephalosporin
4. Fourth generation Cephalosporins

• Fourth-generation cephalosporins are
  extended-spectrum agents with similar activity
  against Gram-positive organisms as
  first-generation cephalosporins.
• They also have a greater resistance to
  beta-lactamases than the third-generation
  cephalosporins.
• Many can cross the blood-brain barrier and are
  effective in meningitis.
• They are also used against Pseudomonas
  aeruginosa.

Cefozopran Cefpirome (Cefrom) Cefquinome
Cefclidine Cefepime (Maxipime) Cefluprenam
Cefoselis
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Classification of Cephalosporin
5. Fifth generation Cephalosporins

• Ceftobiprole has been described as "fifth
  generation" though acceptance for this
  terminology is not universal.
• Ceftobiprole (and the soluble prodrug medocaril)
  are on the FDA fast-track.
• Ceftobiprole has powerful antipseudomonal
  characteristics and appears to be less
  susceptible to development of resistance.

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