Lecture 7 Chapter 25 Antibacterials: Penicillins & Cephalosporins.
Cephalosporins
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Transcript of Cephalosporins
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