The document discusses cephalosporins, a group of semisynthetic antibiotics derived from the fungus Cephalosporium acremonium. It provides historical background on their discovery in the 1940s and describes their mechanism of action as disrupting bacterial cell wall synthesis like penicillins. The document categorizes cephalosporins into four generations based on their spectrum of activity, with later generations having greater coverage of gram-negative bacteria and being more resistant to bacterial beta-lactamases. A range of therapeutic uses and some adverse effects are also summarized.

1. SANJIB KUMAR YADAV
M.PHARM(PHARMACOLOGY)
LECTURER, DEPARTMENT OF PHARMACY,
CHHINNAMASTA EDUCATIONAL ACADEMY,
RAJBIRAJ, NEPAL
Yadavsanjibkumar@gmail.com
CEPHALOSPORINS

2. HISTORICAL BACKGROUND
 The cephalosporins are isolated from cephalosporium species and prepared
semisynthetically.
 In 1945 AD Giuseppe bortzu discovered that the cultures of cephalosporium
acremonium inhibited the growth of various gram +ve and gram –ve
bacterias.
 Crude filtrates inhibit invitro S. aureus; Cured staphylococcal and typhoid
infections.
 In 1948 AD Guy Newton & Edward Abraham discovered Cephalosporin-C.

3. INTRODUCTION
 These are the group of semisynthetic antibiotics Isolated from fungus
“Cephalosporinum acremonium”.
 Chemical structure comprises, β – lactam ring, dihydrothiazide ring and
acyl side chain.
 Chemically similar to penicillin, so it shares the mechanism of action
and adverse effects with that.

4. CEPHALOSPORINS Vs PENICILLINS
Cephalosporins are ,
 More acid stable.
 More resistant to β –lactamase (cephalosporinase)
degradation.
Therefore have a broad spectrum of activity against
Gm –ve bacteria and anaerobes compared to
penicillin .

5. CLASSIFICATION

6. MECHANISM OF ACTION
 Cephalosporins are bactericidal and have the same mode of action as
other beta-lactam antibiotics (such as penicillin).
 Cephalosporins disrupt the synthesis of the peptidoglycan layer of
bacterial cell walls.
 The peptidoglycan layer is important for cell wall structural integrity.
 So, it cause osmotic imblance, further leads to bacterial cell lysis and
death.

7. PHARMACOKINETIC
 . Except 1st and some of 2nd and 3rd generation, all cephalosporins are
adminstered parentrally.
 Well distributed in body fluids.
 Crosses placenta and secreted in breast milk.
 20-30% bound to plasma proteins.
 Metabolise in liver.
 80-90% excreted unchanged in urine.
 Elimination occurs through tubular secretion/glomerular filtration.
 Cefoperazone and ceftriaxone are excreted through bile.

8. THERAPEUTIC USES
They are uses in treatment of:
• Alternative to Pn G (particularly in allergic patients not in anaphylactic reaction).
• H.influenza infection :
E.g : Cephalexin (I)< Cefazolin (I)< Cefuroxime (II)< Cefaclor (II)<Cefixime(III)
• Respiratory , urinary and soft tissue Gm –ve infections.
E.g: cefuroxime (II),cefotaxime (III), ceftriaxone(III)
• Septicaemias (Gm-ve).
E.g: cefotoxime(III),ceftriaxone(III),cefoperazone(III),cefepime(IV),cefprione(IV).

9. • Surgical prophylaxis
E.g : Cefazolin(I)
• Meningitis : (gm-ve)
E.g: cefotaxime (III), ceftriaxone (III) & ceftazidime (III).
• Gonorrhoea: (pen.p.org)
E.g: ceftriaxone(III) , cefuroxime(II),cefotaxime (III).
• Typhoid fever
E.g cefoperazone (III), ceftriaxone (III).
• Mixed infection (aerobic + anaerobic)
cancer, colorectal surgery and obstetric complications (peritonitis,diverticulitis).
E.g: cefuroxime (II).

10. • Hospital acquired infection like pneumonia.
E.g: cefotaxime(III), ceftizoxime (III), cefiprime (IV), cefipirone(IV).
• Prophylaxis and treatment for neutropenic patients .
E.g : ceftazidime (III).

11. ADVERSE EFFECTS
• Pain after I.m injection
• Diarrhoea
• Hypersensitive reaction
• Nephrotoxicity-E.g: cephalothin
• Bleeding disorders due to hypoprothrobinemia
E.g: cefoperazone(III), ceftriaxone (III).
• Thrombocytopenia and neutropenia . E.g : ceftazidime (III).
• Disulfiram like reaction – cefoperazone (III), cefotetan (II)

12. DOSES
1st generation
Drug Usual dose
Cefadroxil 500mg-1G (bid)
Cefazolin 500mg-2G/8hour
Cephalexin 250mg-500mg/6houly
Cephradine 250mg-500mg/6houly
2nd generation
Drug Usual dose
Cefaclor 250-500 mg/8 hour
Cefuroxime 750mg-1.5 G/8hour
Cefoxitin 1-2 G /6-8 hour(max 12 G/day )

13. 3rd generation
Drug Usual dosage
Cefotaxime 1-2 G 6-12 hourly
Ceftriaxone 1-4 G/24 hours
Ceftazidime 1-2 G 8-12 hourly
4th generation
Drug Usual dose
Cefipime 2 G(bid ) for 10 days

14. Contraindication:
-Hypersensitivity
- Renal impairment
Precaution:
- Lactation
- Pregnancy

15. FIRST GENERATION
 Developed in 1960 AD.
 Have high activity against Gram +ve but weaker
against
Gram –ve bacteria
 Cephalothin -1st cephalosporin used clinically
 Active against- streptococci, staphylococci,
gonococci meningococci etc.

16. SECOND GENERATION
 More active against Gram –ve organisms Some
members active against anaerobes
 Cafoxitin highly resistant to β-lactamases
produced by
gram –ve bacteria.
 Used in- surgical infections , lung abscess

17. THIRD GENERATION
 Introduced in 1980AD
 Highly active against gram-ve bacteria
 All are highly resistant to β-lactamases from gram
–ve bacteria
 Cefotaxime:Potent action on aerobic gram-ve as
well as gram+ve bacteria, Not so active on
anaerobes. USE
 Treat: Hospital acquired infections, Septicaemias,
Infections in immunocompromised patients.

18. FOURTH GENERATION CEPHALOSPORINS
 Developed in 1990AD
 Highly resistant to β-lactamases.
 Active- P.Aeruginosa and S.aureus.