CEPHALOSPORINS BY: MS. SABA INAYAT ALI

DEFINITION Any of various broad-spectrum beta- lactam antibiotics closely related to the Penicillins, that were originally derived from the fungus, Cephalosporium acremonium

INTRODUCTION ACTION: Inhibitors of cell wall synthesis COMMON USE: In surgical procedures- to reduce the risk of post- operative infections.

CLASSIFICATION 4 Generations- based upon: The spectrum of antimicrobial activity Grouped w.r.t increased Gm. Negative & decreased Gm. Positive activity

FIRST GENERATION Cefazolin Cephalexin Spectrum:Most Gm. +ve cocci (Strep, S.aureus), E.coli, proteus, Klebisella Use: S.aureus infection, surgical prophylaxis

SECOND GENERATION Cefoxitin Cefuroxime Cefaclor Cefprozil Spectrum: mainly effective gram negative bacteria, modest activity against gram positive bacteria Use: primarily for upper & lower respiratory tract infections

THIRD GENERATION Ceftriaxone Cefotaxime Spectrum: enhanced gm. –ve activity Use: Meningitis, highly resistant & multi drug resistant Strepto pneumo along with vancomycin

FOURTH GENERATION Cefepime Spectrum: active against Strep, staphylo, aerobic gm. -ve

It is possible to convert penicillin V or Benzyl penicillin to a cephalosporin by chemical ring expasion. The first generation cephalosprin Cephalexin, for example, can be made by this way. Most cephalosporins used in clinical practice are semi-synthetics produced from the fermentation product cephalosporin C

Cephalosporium acrimonium Most common in: Soil Plant debris Rotting mushrooms

Cephalosporins Cephalosporin C was first isolated in 1952. Cephalosporin C is made as the fermentation product of Cephalosporium acremonium. However, this form is not potent for clinical use. Its molecule can be transformed by removal of an aminoadipic acid side chain to form 7-α aminocephalosporanic acid (7-ACA), which can be further modified by adding side chains to form clinically useful broad spectrum antimicrobials

Cephalosporins Various side chains can be added to as well as removed from both 6-APA and 7-ACA to produce antibiotics with varying spectra of activities and varying degrees of resistance to inactivation by enzymes produced by pathogenic microbes.

Production Fermentation conditions are rather similar to those with penicillin but methionine is added to increase production

Medium The initial defined medium contained Glucose, Ammonium chloride, Methyl oleate, Metallic salts… little cephalosporin C was obtained Production of cephalosporin C was induced by methionine, which cause the necessary thickening of the mycelium & raised cephalosporin C production to about 4g/L

Fermentation Conditions fermentation is advantageously carried out at a temperature preferably about 25° C., at a pH of from 5-8 and preferably about 6, and for from 1-20 days, preferably 4-10 days.

Recovery of Antibiotic The product is extracted from the culture fluid by adsorption on to carbon or resins rather than by solvent