CEPHALOSPORINS

INTRODUCTION

These are a group of semi synthetic antibiotics derived from cephalosporin C obtained from a fungus Cephalosporium. Nucleus consist of b lactam ring fused to dihydrothiazine ring. Cephalosporin compounds were first isolated from cultures of Cephalosporium acremonium from a sewer in Sardinia in 1948 by Italian scientist Giuseppe Brotzu. The first agent cephalothin (cefalotin) was launched by Eli Lilly in

MODE OF ACTION
Cephalosporins are bactericidal agents and 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, which causes the walls to break down and eventually the bacteria die.

Indications
Cephalosporins are indicated for the treatment of bacterial infections caused by susceptible organisms. First generation cephalosporins are predominantly active against gram-positive bacteria, and successive generations have increased activity against gram-negative bacteria (often with reduced activity against gram-positive organisms). Cephalosporins are used to treat a wide variety of bacterial infections, such as respiratory tract infections (pneumonia, strep throat, tonsillitis, bronchitis), skin infections and urinary tract infections. They are sometimes given with other antibiotics. Cephalosporins are also commonly used for surgical prophylaxis - prevention of bacterial infection before, during, and after surgery.

FIRST GENERATION CLASSIFICATION

PARENTERAL CEFALOTHIN CEFAZOLIN ORAL CEPHALEXIN CEPHRADINE CEFADROXIL

CEPHALEXIN
It is an orally effective first generation cephalosporin most commonly used cephalosporin Spectrum is similar to cefazolin, but less effective against pencillinase producing Staphylococci and H. influnzae. Little bound to plasma protiens, attains high concentration in bile and exerted unchanged in urine DOSE: 0.25-1g 6-8 hourly (children 25100mg/kg/day

CEFADROXIL
Close congener of cephalexin; has good tissue penetration,exerts more sustained action at site of infections It is excreted unchanged in urine,but dose need to be reduced only if creatinine clearence is <50ml/ min The antibacterial activity and indication are similar to cephalexin DOSE: 0.5-1gm BD

SECOND GENERATION CEPHALOSPORIN

More active against gram negative organism Some members active against anarobes, but none active against P.aeruginosa

SECOND GENERATION CLASSIFICATION

PARENTERAL

ORAL

CEFUROXIME CEFOXITIN

CEFACLOR CEFUROXIME AXETIL

CEFUROXIME
It is resistant to gram-negative lactmases:highly active against organisms producing these enzymes including PPNG(Penicillinase producing N.gonorrhoeae) and ampicillin-resistant H. influnzae It is well tolerated by i.m.route and attains higher CSF levels It has been empolyed for single dose i.m. therapy of gonorrhoea due to PPNG.

 Cefuroxime

axetil-

This ester of cefuroxime is effective orally Its activity depends on in vivo hydrolysis and release of cefuroxime. Dose= 250-500mg BD Cefaclor It retain significant activity by oral route and is more active than first generation compounds against H.influenzae,E.coli and Pr.mirabilis. Dose= .25-1gm 8 hourly

Third Generation (Cephalosporin)

It have activity against G-ve bacteria enterobacteiaceae and some inhibit pseudomonas. All are highly resistant to b-lactamases from G-ve bacteria. Less active on G+ve bacteria.

Classification
PARENTERAL
CEFOTAXIME CEFTIZOXIME CEFTRIAXONE CEFTAZIDIME CEFOPERAZONE

ORAL
CEFIXIME CEFPODOXIME PROXETIL CEFDINIR CEFTIBUTEN

CEFOTAXIME
Prototype of third generation cephalosporin ,exert potent action on aerobic G-ve bacteria and some G+ve bacteria. Prominent indications are meningitis(caused by G-ve bateria),life threatening resistant/hospital acquired infection ,septicaemia and infection in immunocompromise patients. Dose= 1-2 gm or i.v. 6-12 hourly(children 50-100 mg/kg/day).

Cefpodoxime proxetil
It is the orally active ester prodrug of cefpodoxime Highly active against enterobacteriaceae, streptococci and inhibit staph aureus. Used mainly for respiratory,urinary,skin and soft tissue infection. Dose= 200mg BD(max. 800gm /day)

FOURTH GENERATION CEPHALOSPORIN

PARENTRAL CEFIPIME CEFPIROME

cefepime
Antibacterial spectrum similar to 3rd generation compound, but is highly resistant to lactase Ps aeruginosa and Staph aureus are also inhibited Effective in serious infections like hospital acquired pneumonia, febrile nutropenia,bacterimia,septesemia DOSE: 1-2gm (50mg/kg) i.v. 8hourly

Cefpirome
Indicated for treatment of serious and resistant hospital acquired infections including septesemia,lower respiratory tract infection its zwitter ion character permits penetration through porion channel of gram negative bacteria