1. BY
V. SUSHIL

2. THEY ARE ANTIBIOTICS, CHEMICALLY
RELATED TO PENICILLINS, DERIVED
FROM ‘CEPHALOSPORIN-C’ .
CEPHALOSPORIN-C WAS ISOLATED BY
GUY NEWTON & EDWARD ABRAHAM.
CEPHALOSPORINS WERE FIRST
ISOLATED FROM CULTURES OF
Cephalosporium acremonium, a
fungus, by an Italian scientist ‘GIUSEPPE
BROTZU’.
HE NOTICED THAT THEY WERE
EFFECTIVE AGAINST Salmonella typhi
(typhoid fever) WHICH HAD BETA-
LACTAMASES.

3. CEPHALOSPORIUM
CULTURE (COLONIES) MICROSCOPIC VIEW
Cephalosporium acremonium

4. BY ADDITION OF DIFFERENT SIDE CHAINS:
 AT POSITION 7 (beta-lactam ring) antibacterial
spectrum against specific organisms can be altered.
At position 3 of dihydrothiazine ring , pharmacokinetics
can be altered as required.

5. Mechanism of action
 Inhibition of bacterial
cell wall synthesis, similar
mechanism as that of
penicillin.
Transpeptidases enzyme
is inhibited leading to
failure of cross linking of
peptide chains of strands,
no stability to cell wall.
Bactericidal action is
exhibited by lysis of cell
wall deficient
forms(CWD’s).

6. RESISTANCE
 Acquired resistance to cephalosporin could
be due to:
1.Alteration in the target proteins.
2.Impermeability to the antibiotic preventing
it from reaching its site of action.
3.Cephalosporinases(beta lactamases)
against specific cephalosporins
 They are not susceptible to hydrolysis by
staphylococcal penicillinase.
 Cephalosporins may be susceptible to
extended- spectrum Beta-lactamases.
E.g. Cefazolin is susceptible to
staphylococcal Beta-lactamase.

7. PHARMACOKINETICS
Administration:
Many of the
cephalosporins
must be
administered IV or
IM ,but oral
cephalosporins
have also been
developed
All cephalosporins
distribute very well into
body fluids. However,
adequate therapeutic
levels in the CSF,
regardless of
inflammation, are
achieved only with the
third-generation
cephalosporins. For
example, ceftriaxone or
cefotaxime are effective
in the treatment of
neonatal and childhood
meningitis caused by
Haemophilus influenzae.
Elimination:
It occurs through
tubular secretion and
glomerular
filtration.Therefore
doses must be
adjusted in cases of
severe renal failure to
guard against
accumulation and
toxicity. Ceftriaxone is
excreted through the
bile into the feces and
therefore, is
frequently employed
in patients with renal
insufficiency.
Distribution:
All cephalosporins
cross the placenta.

8. FIRST GENERATION SECOND GENERATION
THIRD GENERATION FOURTH GENERATION
CEPHALOSPORINS
ORAL
CEPHALEXIN
CEPHRADINE
CEFADROXIL
PARENTERAL
CEPHALOTHIN
CEFAZOLIN
ORAL
CEFACLOR
CEFUROXIME-
AXETIL
CEFPROZIL
PARENTERAL
CEFUROXIME
CEFOXITIN
ORAL
CEFIXIME
CEFDINIR
CEFTIBUTEN
CEFPODOXIME-
PROXETIL
CEFTAMET
PIVOXIL
PARENTERAL
CEFOTAXIME
CEFTIZOXIME
CEFTRIAXONE
CEFTAZIDIME
CEFOPERAZO-
NE
PARENTERAL
CEFEPIME
CEFPIROME

9. CHARACTERISTICS AND ACTIONS:
 Prototype first generation
cephalosporin.
 Mainly used as penicillin G
substitute.
 Long plasma half –life (2
hours) , longer duration of
action, hence used for
surgical prophylaxis.
 Dose :0.25g 8hourly(mild
cases) i.m. / i.v.
1g 6hourly(severe
cases) i.m. / i.v.
CEFAZOLIN
Streptococcus pyogenes
Streptococcus viridans
Streptococcus pneumoniae
Gonococci, meningococci
Klebsiella
E.Coli
Proteus
mirabilis
ActinomycesClostridia

10. CEPHALEXIN
Prototype of first generation , oral
cephalosporin.
Similar in anti-bacterial spectrum to cefazolin.
High concentrations attained in bile, excreted
unchanged in urine.
Plasma half-life 1 hour.
Dose: 0.25-1g 6 to 8 hourly.
children 25-100 mg/kg/day
 used in treatment of minor infections like
abscess, cellulitis,pharyngitis.

11. FIRST GENERATION CEPHALOSPORINS
 Orally active drug , also
available for parenteral
use.
 Dose: 0.25-1g 6-12
hourly oral/i.m/i.v.
 Good tissue penetration
and sustained action at
site of infection.
 Plasma half –life 1 hour,
can be given 12 hourly.
 Dose: 0.5-1g BD.
CEPHRADINE CEFADROXIL

12. SECOND GENERATION CEPHALOSPORINS
 They are more active against gram negative
bacteria, and some anaerobes.
Clinically, largely replaced by third generation
cephalosporins.
CEFUROXIME
 Resistant to gram-negative beta-lactamases.
Well tolerated by i.m route and crosses the blood –
brain barrier, attains higher CSF levels.
 Dose: 0.75-1.5g i.m/i.v. 8 hourly.
children: 30-100 mg/kg/day

13. CEFACLOR
 Orally effective second generation drug.
Serum sickness-adverse effect seen in
some cases.
Dose: 0.25-1 g 8 hourly.
CEFOXITIN
 Good activity against anaerobes,
particularly Bacteroides
fragilis.
Useful in patients with intra-
abdominal sepsis and
against gynecologic sepsis,
pelvic inflammatory disease.

14. CEFUROXIME AXETIL
 This is an ester of cefuroxime.
Orally effective, cefuroxime is released by hydrolysis in the
body.
Dose: 0.25-1.0g 8 hourly.
THIRD GENERATION CEPHALOSPORINS
GRAM
NEGATIVE
BACILLI
ENTEROBACTER
PSEUDOMONAS
GRAM ‘-’
COCCI
NEISSERIA
GONORRHOEA
GRAM +
COCCI

15. THIRD GENERATION CEPHALOSPORINS
Prototype of third generation
cephalosporin.
 potent action on aerobic gram
negative bacteria.
Used against meningitis caused
by gram negative
bacilli,septicaemias,hospital
acquired infections.
Attains high CSF levels.
 plasma T1/2-1hr.
 DOSE:1-2gm i.m or i.v. 8-12 hrly.
CEFOTAXIME

16. Potent action against Bacteroides
fragilis.
Plasma T1/2 1.5-2hr.
DOSE:0.5-2gm i.m/i.v. 8-12hrly.
Longest duration of action(plasmaT1/2 -8hrs).
Good CSF penetration.
USES:
Bacterial meningitis.
Multiresistant typhoid fever.
Urinary tract infections.
Abdominal sepsis.
ADVERSE EFFECTS:
Hypoprothrombinemia & bleeding.
Haemolysis in some cases.
CEFTIZOXIME
CEFTRIAXONE

17. High activity against pseudomonas.
Plasma T1/2 1.5-1.8hr.
USES:
Febrile neutropenic patients with haematological
malignancies,burns.
DOSE:0.5-2gm i.m/i.v. 8hrly.
Children:30mg/kg/day.
Stronger activity on pseudomonas.
Susceptible to beta-lactamases.
Plasma T1/2-2hrs.
Disulfiram –like reaction with alcohol reported in some cases.
Indications :severe urinary billiary respiratory
infections,skin&soft tissue infections.
DOSE:1-3gm i.m/i.v. 8-12hrly.
CEFTAZIDIME
CEFOPERAZONE

18. Oral third generation drug highly active
against enterobactericiae,Haemophilus
influenzae.
Resistant to many beta-lactamases.
Longer action;T1/2 -3hrs.
DOSE:400mg BD
Orally active ester prodrug of cefpodoxime.
Inhibits staphylococcus aureus.
Also active against
enterobacterioceae&streptococci.
USES:respiratory,urinary,skin infections.
Dose:200mg BD
CEFPODOXIME
PROXETIL
CEFIXIME

19. CEFDINIR
 Potent against
respiratory
pathogens(gram
positive cocci).
 Indications:pneumonia
acute exacerbation of
chronic bronchitis,ENT
infections.
 Dose:300mg BD
 Orally acting,stable to
beta-lactamases.
 Active against gram
positive &gram
negative
bacteria(except
pneumococci,staphyloc
occus aureus)
 plasmaT1/2 2-3hrs.
 Dose:200mg BD 400mg OD.
CEFTIBUTEN

20. FOURTH GENERATION CEPHALOSPORINS
CEFEPIME
CEFPIROME
Better penetration through porin channels of
gram ‘-’ bacteria due to zwitterion nature.
Indications: resistant hospital acquired
infections,septecaemias.
Dose: 1-2 g i.m/i.v. 12hourly
Highly resistant to beta-lactamases.
High potency against Pseudomonas
aeruginosa &Staph. aureus.
Dose: 1-2g i.v. 8-12hourly

21. ADVERSE EFFECTS
 PAIN: i.m. or i.v. infusion is usually painful.
severe pain with cephalothin is experienced.
thrombophlebitis of injected vein can occur.
 Diarrhoea : mostly seen with cephradine and cefoperazone(due
to excretion in bile).
 Nephrotoxicity: cephalothin,cephaloridine exhibit renal toxicity
when administered. Ceftriaxone is excreted mostly in bile
hence, used in patients with renal insufficiency. It also has
good bone penetration.(cefazolin)
 Bleeding: due to hypoprothrombinaemia seen commonly in
patients with cancer, renal failure.
 Ceftazidime has been associated with neutropenia ,
thrombocytopenia.

22. Hypersensitivity: incidence is lower than
pencillins.10% penicillin allergic patients
exhibit cross-sensitivity to cephalosporins.
Frequent manifestations:
rashes,anaphylaxis,angioedema,asthma and
urticaria

23. THROMBOPHLEBITIS OF INJECTED VEIN

24. FIFTH GENERATION CEPHALOSPORINS
CEFTAROLINE:
Advanced generation cephalosporin antibiotic.
Active against MRSA & gram positive bacteria.
Being investigated for community acquired bacterial pneumonia &
complicated skin & skin structure infection.
Has received approval from U.S. FDA.
BINDS TO & INHIBITS ‘PBP-2a’( type
produced by MRSA)
Clinical trials- common adverse
effects:diarrhoea, nausea, rash.
Known serious hypersensitivity &
anaphylactoid reactions have been reported.
TEFLARO

25. CEFTOBIPROLE
Activity against MRSA ,penicillin resistant Streptococcus
pneumoniae, Pseudomonas aeruginosa, Enterococci.
Inhibits the 2a PBP of MRSA, 2X PBP of Strep. pneumoniae.
Given i.v. , but not FDA approved for use in children.
 is under review , approved in some countries.

26. TYPHOID (ALTERNATIVES TO
FLUOROQUINOLONES)
CEFTRIAXONE
4 g x 2 days, followed by
2 g x 2 days
GONORRHOEA -
PENICILLIN PRODUCING
CEFTRIAXONE
CEFUROXIME
250 mg i.m
250 mg i.m
MENINGITIS BACTERICIDAL ACT. IN
CSF.CEFTRIAXONE/CEFO
TAXIME
INFECTIONS-GRAM ‘–’
BACTERIA
CEFUROXIME
CEFOTAXIME 1-2 g i.m / i.v. 12 hrly
SURGICAL
PROPHYLAXIS
CEFAZOLIN
ALTERNATIVES TO
PnG(ALLERGIC)
CEFAZOLIN
CEPHALEXIN
0.25 g 8 hrly
0.25-1 g 6-8 hrly
HOSPITAL ACQUIRED
INFECTIONS
CEFOTAXIME
CEFEPIME 1-2 g i.v. 12 hrly
INFECTIONS IN CEFTAZIDIME 0.5-2 g i.m /i.v. 8 hourly
INDICATIONS OF CEPHALOSPORINS

27. USE ANTIBIOTICS JUDICIOUSLY!
THANK Q