This document provides an overview of cephalosporins, a class of beta-lactam antibiotics. It describes their classification into four generations based on their spectrum of activity and other properties. Key points include: Cephalosporins are derived from the fungus Cephalosporium and are bactericidal by inhibiting bacterial cell wall synthesis. Their classification is based on their spectrum of activity, with later generations having increased activity against gram-negative bacteria. Common examples from each generation like cefazolin, cefuroxime, cefotaxime, and cefepime are described along with their indications, dosages, and adverse effects.
3. Cephalosporins
Beta- lactam antibiotics
Closely related both structurally and functionally to the penicillins
Most cephalosporins are produced semisynthetically
Derived from cephalosporin- C
Obtained from a fungus Cephalosporium
Bactericidal
MOA: Bacterial cell wall synthesis inhibition
Nucleus consists of a beta- lactam ring fused to a dihydrothiazine ring
5. First Generation Cephalosporins
Developed in 1960s
Act as Penicillin G substitutes
Have high activity against gram positive bacteria
Weaker against gram negative bacteria
They are resistant to the Staphylococcal penicillinase
Cefazolin
Prototype first generation cephalosporin
Active against most Penicillin G sensitive organisms (eg. Streptococci,
gonococci, meningococci, H. influenzae)
Acivity against Klebsiella, Moraxella catarrhalis and E.coli is relatively
high
6. It is the preferred parenteral first generation cephalosporin, especially for
surgical prophylaxis
Dose: 0.5 g 8 hourly (mild cases)
1 g 6 hourly (severe cases)
Children: 25-50 mg/kg/day i.m or i.v
Cefalexin
Most commonly used
Effective orally
Less active against penicillinase producing staphylococci and H.
influenzae
Plasma protein binding is low; it attains high concentration in bile
Excreted unchanged in urine; Plasma half life: ~60 min
7. Second Generation Cephalosporins
Developed subsequent to the first generation compounds
More active against gram negative organisms
With some members active against anaerobes
Weaker than first generation compounds against gram positive bacteria
Their utility has declined in favour of the 3rd generation agents
Cefuroxime
Resistant to gram negative beta- lactamases: has high activity against
organisms producing these enzymes including PPNG and ampicillin
resistant H. influenzae
Retaining significant activity on gram positive cocci and certain
anaerobes but not B. fragilis
8. It is well tolerated by i.m. route
Attains relatively higher CSF levels
It can be employed for single dose i.m. therapy of gonorrhoea due to PPNG
Dose: 0.75-1.5 g i.m. or i.v. 8 hourly
Children: 30-100 mg/kg/day
Cefuroxime axetil
Ester of cefuroxime
Orally effective
Absorption is incomplete
The activity depends on in vivo hydrolysis and release of cefuroxime
Dose: 250-500 mg BD
Children half dose
9. Third Generation Cephalosporins
Introduced in the 1980s
Have highly augmented activity against gram positive
Enterobacteriaceae
Few members inhibit Pseudomonas
All are highly resistant to beta- lactamases from gram negative bacteria
Less active on gram positive cocci and anaerobes
Cefotaxime
Prototype third generation cephalosporin
Exerts potent action on aerobic gram negative as well as some gram
positive bacteria
Not active on anaerobes, Staph. Aureus and Ps. aeruginosa
10. Prominent indications are meningitis caused by gram negative bacilli, life
threatening resistant/ hospital- acquired infections, septicaemias and
infections in immunocompromised patients.
An alternative to ceftriaxone for typhoid fever
Plasma half life: 1 hr
Cefotaxime is deacetylated in the body
Penetration into CSF is good
Dose: 1-2 g i.m./ i.v. 6-12 hourly
Children 50-100 mg/kg/day
Cefixime
Orally active third generation cephalosporin
Highly active against Enterobacteriaceae, H. influenzae, Strep. pyogenes
11. Resistant to many beta lactamases
It is not active on Staph. aureus, most pneumococci and Pseudomonas
Longer activity: Plasma half life- 3 hr
Penetration into CSF is good
Dose: 200-400 mg BD for respiratory, urinary, and biliary infections
Side effects: Stool changes and diarrhoea
Cefpodoxime proxetil
Orally active ester prodrug of 3rd generation cephalosporin cefpodoxime
Highly active against Enterobacteriaceae and streptococci
It inhibits Staph. aureus
Uses: Respiratory, urinary, skin and soft tissue infections
Dose: 200 mg BD (max 800mg/day)
12. Fourth Generation Cephalosporins
The distinctive feature of this last developed subgroup of cephalosporin
is non- susceptibility to inducible chromosomal beta lactamases in
addition to high potency against Enterobacteriaceae
Cefepime
Developed in 1990s
Antibacterial spectrum similar to that of 3rd generation compounds
Highly resistant to beta lactamases
Plasma half life: 2 hours
Higher concentrations are attained in the CSF
Excreted by the kidney
Use: Hospital acquired pneumonia, febrile neotropenia, bacteraemia
Dose: 1-2 g i.v. 8-12 hourly
13. Adverse effects: Cephalosporins
Pain after i.m. injection
Diarrhoea
Hypersensitivity reactions
Nephrotoxicity, Neutropenia and thrombocytopenia
Uses: Cephalosporins
Respiratory, urinary and soft tissue infections
Penicillinase producing staphylococcal infections
Surgical prophylaxis and Meningitis
Gonorrhoea caused by penicillinase producing organisms
As alternatives to penicillin for ENT, upper respiratory and cutaneous
infections