This document provides an overview of cephalosporins, a class of beta-lactam antibiotics. It discusses the history of cephalosporins, noting they were first isolated from fungus. It describes the mechanisms of action of cephalosporins in inhibiting bacterial cell wall synthesis. The document also classifies cephalosporins into five generations with varying spectra of activity and lists examples of first to fifth generation cephalosporins along with their pharmacokinetic properties and clinical uses.

1. CEPHALOSPORINS
CEPHALOSPORINS
PRESENTED BY:
J.Manohar Reddy
REG NO Y19MPH0252
DEPARTMENT OF PHARMCOLOGY
HINDU COLLEGE OF PHARMACY
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2. CEPHALOSPORINS
Introduction
History
Cephalosporins work
Classification
Mechanism of Action
Mechanisms Of Resistance
Adverse Reactions
Uses
References
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3. CEPHALOSPORINS
Introduction
Cephalosporins N,C or P - steroidal antibiotic that resembles fusidic
acid.
first isolated from Cephalosporium fungus
Semisynthetic broad-spectrum cephalosporins- produced by
addition, to the cephalosporin C nucleus
water-soluble and relatively acid-stable
cephamycins are β-lactam antibiotics -Streptomyces organisms
– closely related to the cephalosporins3

4. CEPHALOSPORINS
History
In 1945 Giuseppe Brotzu`s discovered that cultures of
Cephalosporium acremonium inhibited the growth of a
wide variety of Gram-positive and Gram-negative bacteria.
He noticed that these cultures produced substances that were
effective against Salmonella typhi, Researchers at the Sir
William Dunn School of Pathology at the University of Oxford
isolated cephalosporin C, which had resistance to β-lactamases
but was not sufficiently potent for clinical use.
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5. CEPHALOSPORINS
Cephalosporins work
Cephalosporins are bactericidaland have the same mode of
action as other beta-lactam antibiotics (such as penicillins).
Cephalosporins disrupt the synthesis of the peptidoglycan layer
of bacterial cell walls.
The peptidoglycan layer is important for cell wall structural
integrity.
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6. CEPHALOSPORINS
Cephalosporins work
The final transpeptidation step in the synthesis of the
peptidoglycan is facilitated by transpeptidases known as
penicillin binding proteins (PBPs).
PBPs bind to the D-Ala-D-Ala at the end of muropeptides
(peptidoglycan precursors) to crosslink the peptidoglycan.
beta-lactam antibiotics mimic this site and competitively inhibit
PBP crosslinking of peptidoglycan.6

7. CEPHALOSPORINS
Classification
Cephalosporins can be broadly categorized into five
generations.
Oral Classification
Generation Oral Agents
1st generation Cefadroxil, cephalexin, cephradine
2nd generation Cefaclor, cefprozil, cefuroxime axetil
3rd generation Cefdinir, cefditoren, cefpodoxime
proxetil, ceftibuten, cefixime, Ceftamet
pivoxil
4th generation
5th generation
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8. CEPHALOSPORINS
Parenteral Classification
Generation ParenteralAgents
1st generation Cefazolin, Cephalothin
2nd generation Cefuroxime, cefoxitin, Cefotetan
3rd generation Cefotaxime, ceftazidime, ceftizoxime,
ceftriaxone, Cefoperazone
4th generation Cefepime, cefpirome
5th generation Ceftaroline, Ceftobiprole
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9. CEPHALOSPORINS
Mechanism of Action
Cephalosporins
Bind & inactivate CBP on cell wall of susceptible bacteria
Inhibit transpeptidase
Prevent peptidoglycan synth
Cell wall deficient forms
Autolysis & cell death9

10. CEPHALOSPORINS
Mechanism of Action
Cephalosporins and cephamycins inhibit bacterial cell wall
synthesis in a manner similar to that of penicillin.
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11. CEPHALOSPORINS
Mechanisms Of Bacterial Resistance
Inactivation of antibiotic by β- lactamase
Alteration of binding site.
Modification of target PBPs
Impaired penetration of drug to target PBPs
Antibiotic efflux
Decrease permeability.
Production of β–lactamase enzymes (enzymatic inactivation)
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12. CEPHALOSPORINS
Mechanisms Of Bacterial Resistance
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13. CEPHALOSPORINS
First Generation Cephalosporins
These were developed in the 1960s, have high activity against gram-
positive but weaker against gram-negative bacteria.
Active against gram-positive cocci, such as pneumococci,
streptococci, and staphylococci.
Traditional cephalosporins - not active against MRSA strain.
Clinical Use
drug of choice for surgical prophylaxis
urinary tract infections
cellulitis or soft tissue abscess
cannot be used to treat meningitis
Alternative to penicillin allergic individual
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14. CEPHALOSPORINS
Cephalexin(oral)
Pharmacokinetics:
Route of administration: Oral
Partially bound to plasma protiens.
Half life : 60 mins
It attains high concentration in the bile
Excretion through the urine
Adverse effects:
Nausea, diarrhea, vomiting, heartburn .stomach pain .
Uses:
Cephalexin is used to treat certain infections caused by bacteria such
as pneumonia and other respiratory tract infections and infections of
the bone, skin, ears, , genital, and urinary tract14

15. CEPHALOSPORINS
Cefazolin(Parenteral)
Pharmacokinetics:
Route of administration: Parentral , Do not cross BBB
Plasma protein binding is 70 –86%
Volume of distribution -9.2/1.73 sg.meter
Half life - 1.6 – 2.2hours
Renal Excretion -87%
Adverse effects:
Swelling, redness, pain, loss of appetite, nausea, diarrhea, or
headache, vomiting,
Uses:
Cefazolin injection is used to treat certain infections caused
by bacteria including skin, bone, joint, genital, blood, heart valve,
respiratory tract biliary tract, and urinary tract infections15

16. CEPHALOSPORINS
Second Generation Cephalosporins
More active against gram negative organism, with some
members active against anerobes
Clinical Use
treat sinusitis, otitis, and lower respiratory tract infections
treat mixed anaerobic infections such as peritonitis, diverticulitis,
and pelvic inflammatory disease
less effective in treatment of meningitis16

17. CEPHALOSPORINS
Cefaclor(Oral)
Pharmacokinetics:
Route of administration: Oral
Cefaclor is not metabolized to a significant degree, but it degrades
chemically in the body
with an approximate half-life of 2 hours.
Most of the drug is excreted unchanged in the urine
Adverse effects:
Nausea, diarrhea, vomiting, stomach pain
Uses:
Cefaclor is used to treat certain infections caused by bacteria, such
as pneumonia, the skin, ears, throat, tonsils, and urinary tract.17

18. CEPHALOSPORINS
Cefuroxime(Parenteral)
Pharmacokinetics:
Route of administration: Parentral Only cefuroxime crosses BBB
among 2nd generation.
The ultimate serum half-life was 1.1hour
Excretion of cefuroxime in the urine was almost complete in 24
hours,
Adverse effects:
Nausea, diarrhea, vomiting
Uses:
Cefuroxime is used to treat certain infections caused by bacteria, such
as bronchitis, gonorrhea, Lyme disease18

19. CEPHALOSPORINS
Third generationCephalosporin
Expanded gram-negative coverage, and some are able to cross the
blood-brain barrier
Clinical Use
Treat a wide variety of serious infections caused by organisms that are
resistant to most other drugs
avoided in treatment of enterobacter infections
Hospital Acquire infection
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20. CEPHALOSPORINS
Cefixime(Oral)
Pharmacokinetics:
Route of administration: Oral
In general the half-life of the drug is about 3 to 4 hours and is
not dependent on dose.
The drug is not extensively bound to serum proteins
Adverse effects:
Stomach upset/pain, diarrhea, nausea
Uses:
Cefixime is used to treat certain infections caused by bacteria
such as bronchitis , urinary tract infections20

21. CEPHALOSPORINS
Ceftriaxone (Parenteral)
Pharmacokinetics:
Route of administration: Parentral ,All can cross BBB
it’s t½ : 7-8 hours and high plasma protein binding 90%
Cefotaxime metabolized to active metabolite
Cefoperazone and ceftriaxone excreted through bile
All others major route of excretion is urinary
Adverse effects:
diarrhea, vomiting, blood clots, headache
Uses:
Gonorrhoea: Ceftriaxone DOC for all forms Meningitis21

22. CEPHALOSPORINS
Fourth Generation Cephalosporins
Cefepime (Parenteral)
Pharmacokinetics
cefepime exhibitslinear pharmacokinetic behaviour.
Pharmacokinetic variables are not significantly different between
single- and multiple-dose administration, indicating a lack of drug
accumulation in patients with normal renal function.
Adverse effects:
stomach cramps. bleeding gums, convulsions.
Uses:
Pneumonia, Febrile neutropenia22

23. CEPHALOSPORINS
Fifth Generation Cephalosporins
Ceftaroline (Parenteral)
Bind to and inhibit altered PBP 2a Produced by MRSA and penicillin resistant
Streptococcus Pneumoniae
Retain spectrum of 4th generation cephalosporins and notable increase in activity against
gram positive cocci ( MRSA, streptococcus pneumoniae and pyogenes, enterococcus)
Limited activity against anaerobes
Uses:
Complicated skin and soft tissue infections
Community acquired pneumonia
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24. CEPHALOSPORINS
References
1.Essentials of Medical Pharmacology-
KD TRIPATHI MD
2. The Pharmacological Basis of THERAPEUTICS-
Goodman & Gilman’s
3. Lippincott Illustrated Reviews: Pharmacology
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25. CEPHALOSPORINS
THANK YOU
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