CEPHALOSPORINS

VIJAY NAGDEV

H.O.MU-I

CMCH LARKANA

CEPHALOSPORINS

A class of beta lactam antibiotics

They were first isolated from cultures of cephalosporium acremonium

MECHANISM OF ACTION

Peptidoglycan layer is important for cell wall structural integrity

The final step in synthesis of petidoglycan(Transpeptidation) is fascillitated by transpeptidases(pencillin binding proteins)

Cephalosporins competitively inhibit PBP and disrupt synthesis of peptidoglycan

These are bactricidal agents

THERAPEUTIC USES

Pharyngitis Tonsilitis Bronchitis Pneumonia UTI Skin and bone infections(cefazolin and

ceftriaxone have good penetration into bone) Meningitis( 3rd generation cephalosporins) Surgical prophylaxis

ADVERSE EFFECTS

Diarrhea,nausea,vomitting Pain and inflammation at injection site Pseudomembranous colitis Allergic reactions Disulfiram-like

effect(cefamandole,cefoperazone)because these block oxidation of alcohol.

Bleeding(cefamandole,cefoperazone,ceftriaxone)because these contain MTT side chain(anti vit-k effect)

Seroconversion of direct coombs test from negative to positive.

PHARMACOKINETICS

Except 1st and some of 2nd generation,all cephalosporins are adminstered parentrally

Well distributed in body fluids Crosses placenta and secreted in breast milk. Therapeutic levels in CSF are achieved only with

3rd generation cephalosporins 20-30% bound to plasma proteins 80-90% excreted unchanged in urine Elimination occurs through tubular

secretion/glomerular filtration Cefoperazone and ceftriaxone are excreted

through bile (can be administered in renal insufficiency)

CLASSIFICATION

GENERATIONS

Cephalosporins are divided into five generation based largely on their

Spectrum and Resistance to beta lactamases

Each newer generation has increased activity against G-ve rods and decreased activity against G+ve cocci

First generation

Drug

Cefadroxil

Cefazolin

Cephalexin

Cephradine

Spectrum

Active against G+Cocci: strep.pneumonia, MSSA, S.pyogenesModerately active against a few GNB:E.coli,P.mirabilis,K.pneumoniaNo activity against:Enterococci , MRSA and B.fragilis

THERAPEUTIC USES

Pharyngitis Tonsilitis Otitis Pneumonia UTI Skin infections Bone infections (cefazolin) Surgical prophylaxis (cefazolin is drug of

choice )

DOSAGE

Drug Route Usual dose

Cefadroxil Oral 500mg-1G (bid)

Cefazolin parentral 500mg-2G/8hour

Cephalexin Oral 250mg-500mg/6houly

Cephradine Oral / parentral

250mg-500mg/6houly

2nd generation

Drug

Cefaclor

Cefuroxime

Cefoxitin

Spectrum

Streptococcus pneumoniaStrep.pyogensN.GonorrhoeaeE.ColiK.PneumoniaH.influenzaeProteus mirabilis

THERAPEUTIC USES

Upper RTI (weaker effect) Pneumonia UTI Skin infections Bone infections Gonorrhea Surgical prophylaxis(cefuroxime 1.5 G 1hour

prior ) Meningitis (cefuroxime ; but less effective

than 3rd generation )

DOSAGE

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 )

3rd generation

Drug

Cefotaxime

Ceftriaxone

Ceftazidime

Spectrum

Inferior activity to gram + cocciEnhanced activity against gram –ve organismIncludingN.GonorrheaEnterobacter E.ColiK.PneumoniaAnd Pseudomonas aeruginosa

THERAPEUTIC USES

Gonorrhea(single dose of ceftriaxone;1st line drug)

Meningitis ( good penetration in CSF) Sepsis Typhoid (4G ceftriaxone/day for 2 days,then

2G/day for 2 days) Surgical prophylaxis UTI Intra-abdominal infections

DOSAGE

Drug Usual dosage

Cefotaxime 1-2 G6-12 hourly

Ceftriaxone 1-4 G/24 hours

Ceftazidime 1-2 G 8-12 hourly

4th generation

Drug

Cefipime

Cefpirome

Spectrum

More balanced spectraWith greater resistance to beta lactamases.Modest activity against anaerobesNot active against MRSA

THERAPEUTIC USES

Upper RTI (weaker effect)

Pneumonia UTI

Skin infections

Intra abdominal infections

Febrile neutropenia

DOSAGE

Drug Usual dose

Cefipime 2 G(bid ) for 10 days

5th GenerationCeftaroline Fosamil

CEFTAROLINE FOSAMIL

On 29th october 2010 ceftaroline was approved by FDA(U.S food and drug administration )

It was added as 5th generation cephalosporin

In phase III clinical trials it shown non inferior efficacy with same adverse effects to ceftriaxone.

MECHANISM OF ACTION

Same mechanism of action as for other generations

While it can bind to and inhibit PBP-2A( PBP produced by MRSA) which is not inhibited by others.

THERAPEUTIC USES

Infections caused by MRSA

CAP

Skin infections

PHARMACOKINECTIS AND ADVERSE EFFECTS

Same as of other generations

THANKS