Cephalosporins are a class of beta-lactam antibiotics derived from the fungus Cephalosporium. They are grouped into generations based on their spectrum of antibacterial activity and resistance to beta-lactamases. First generation cephalosporins are effective against gram-positive organisms but have limited activity against gram-negatives. Second generation have greater activity against gram-negatives like Haemophilus influenzae but less against gram-positives. Third generation have even broader gram-negative coverage and better central nervous system penetration. Clinical uses include surgical prophylaxis, treatment of streptococcal and staphylococcal infections, and therapy for infections caused by Haemophilus, Klebsiella

1. CEPHALOSPORINS
1ST AND 2ND GENERATION.
• LEARNING OBJECTIVE
• At the end of lecture students should be able to
know,
• Classification of cephalosporins,
st
• 1 generaton cephalosporins.
• Pharmacokinetics.
• Adminstration.
• Clinical uses.
• CEPHALO-SPORINS
•

2. •
• CEPHALO-SPORINS
• First discovered in 1945 from a Cephalosporium
fungi.
• The cephalosporins (CS) are derivatives of 7-
aminocephalo-sporanic acid.
• They are B-lactam antibiotics
• that are closely related both structurally and
functionally to the penicillins.
• CEPHALO-SPORINS
• Most CS, are produced serine-synthetically by
the chemical attachments of side chains to 7-
aminocephalosporanic acid.
• CSs and cephamycins have the same mode of
action as the penicillins & are effected by the
same resistance mechanisms, but they tend to
be more resistant than the penicillins to B-
lactamases.

3. • CEPHALO-SPORINS
• Commercial drugs derived semi-synthetically.
• Reasons for synthetic modification include:
o Increased acid stability
o Improved pharmacokinetics (oral absorption)
o Broaden antimicrobial spectrum
o Increased activity (decreased resistance due
to destruction)
o Improved penetration
o Increased receptor affinity
o Decreased allergenicity
o Increased tolerance due to parenteral
administration
• ANTI-BACTERIAL SPECTRUM
• Cephalosporins have been classified as first,
second or third generation(now- a-days 4th
generation), largely on the basis of bacterial
susceptibility patterns and resistance to B-
lactamases.
• They are ineffective against methicillin-resistant
staphylococcus
• (MRSA), listeria monocytogenes, clostridium
difficle and the enterococci.
• NAME OF CEPHALOSPORINS
• G1

4. o PO: Cephalexin, Cephradine, Cephadroxil
o Parenteral: Cefapirin, Cefazolin
• G2
o PO: Cefaclor, Loracarbef, Cefprozil,
Cefuroxime
o Parenteral:Cefmetazole,Cefotetan,Cefoxitin.
Cefonacid, Cefamandol.
• G3
o PO: Cefpodoxime, Cefixime, Cefdinir,
Ceftitbuten
o Parenteral: Cefotaxime, Ceftizoxime,
Ceftriaxone, Ceftazidime,
Cefaperazone
• G4 - Cefepime
• FIRST GENERATION
• They act as penicillin “G” substitute that are
resistant to the staphylococcal penicillinase
• (B-lactamase).
• FIRST GENERATION
• First generation displays great activity against
gram positive organisms, but have some activity
against gram negative organisms → e.g proteus
mirabilis,E. coli and klebsiella pneumonia.
• First generation having poor C.S.F Penetrability
and narrow spectrum.
• SECOND GENERATION

5. • They are more effective against gram negative
and less effective against gram positive
organisms as compare to first generation.
• The second generation CSs display greater
activity against 3 additional gram negative
organism, Homophilus influenzae, some
Entrobactera-erogenes and some neisseria
species.
• Having un-reliable C.S.F penetrability and
intermediate spectrum.
• Transition from first generation to third
generation agents
• Transition from first generation to third
generation agents reflects
o 1)Broadening of the Gram (-) organism
spectrum
o 2)Loss of efficacy against Gram (+)
organisms
o 3)Greater efficacy against resistant
organisms (but increased cost)
• PHARMACOKINETICS
• ADMINISTRATION
• All the CS (except cephalexin, cephradine
and cefiximine) must be administered

6. intravenously because of poor oral
absorption.
• DISTRIBUTION
• All of these antibiotics distribute very well
into body fluids.
• However, adequate therapeutic levels in the
C.S.F, regardless of inflammation, are
achieved only with the 3rd generation CS,
because most CS do not penetrate into the
C.S.F.
• FATE
• Biotransformation of Cs by the host is not
clinically important.
• Elimination occurs through tubular secretion &/
OR glomerular filtration,thus doses must be
adjusted in the case of severe renal failure to
guard against accumulation & toxicity.
• SIDE EFFECTS
• Allergic manifestation.
• Disulfiram like effect when patient also takes
alcoholic drinks(cefamandole & cefoperazone.
as seen in alcoholics.Increased hangover effect
of ethanol B/C aldehyde dehydrogenase is
blocked)
• 3)Hypoprothrombinemia & Bleeding disorders
• TOXICITY:Local irritation can produce severe
pain after I/M injection & thrombophlebitis after I/

7. V injection.Renal toxicity,including interstitial
nephritis & even tubular necrosis,has been
demostrated & has caused the withdrawal of
drug.
• 5)SUPERINFECTION:Mostly through 2nd
generation Cephalosporins.
• CLINICAL USES OF CEPHALOSPORINS
• Cephalosporins have been shown to be
effective as therapeutic and prophylactic agents
• Cephalosprins with or without aminoglycosides
are used for serious infections caused by
haemophilus, klebsiella , enterobacter , and
serratia species .
• Cephalosporins can be used as an alternative to
peniciins for a variety of infections especially
streptococcal and staphylococcal infection
where patients are not able to tolerate penicillin .
• CLINICAL USES OF CEPHALOSPORINS
• First generation cephalosporins have been used
for prophylaxis during and after surgery .
• However, they are rarely the drug of choice for
any infection .

8. • Oral drug may be used for the treatment of
UTIs , for minor staphylococcal lesions , or for
soft tissue abscess and cellulitis .
• CLINICAL USES OF CEPHALOSPORINS
• For surgical prophylaxis , first generation
cephalosporins can be administered as they
penetrate most tissues well and are drugs of
first choice .
• Second and third generation cephalosprons
offered no advantage for surgical prophylaxis .
• Infection with anaerobes are preferably treated
with a combination of anti biotic because in
these infection aerobic organisms are also
present .
• Cefoxitin and cefotetan are quite effective
against anaerobes and can be considered for
monotherapy against certain organism.
• CLINICAL USES OF CEPHALOSPORINS
• H. Influenzae infection can be treated both by
second OR third generation cephalosporins
.However,because of their penetration to the
CNS ,3rd generation CS (except cefoperazone)
are effective in meningitis caused by
meningococci , pneumococci , and H. Influenzae
and susceptible gram negative bacilli.

9. • Treatment with some second or third generation
cephalosporins is equivalent or superior to
treatment with a combination of ampicillin and
chloramphenicol for meningitis caused by H.
Influenzae .
• THANKYOU