Cepahlosporins

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Cephalosporins

4 generations

First generation

Cefazolin - Prototype drug

- Active against Gram positive bacteria

- active against most PnG sensitive organisms

- activity against Klebsiella, Moraxella catarrhalis and E.coli is high

- susceptible to staphylococcal Beta lactamase

- i.v or i.m (painul)

- longer t1/2due to slower tubular secretion

- preferred parenteral 1st gen cephalosporin for surgical prophylaxis

PK : donot cross BBB

excreted via kidney

uses - treatment of Staph auerus infections, cephazli DOC for K.pneumonia infections , surgical prophylaxis

Second generaration

- action against Gram positive bacteria is little or less than 1st gen

- Antimicrobial action again Gram negative bacteria is increased.

- cefoxitin are active against anaerobes as well, but none inhibits P. aeruginosa.

Cefuroxime - not active against B.fragilis

- i.m , high CSF levels only one that crosses BBB

2. Cefuroxime axetil - ester of cefuroxime

- esteris hydrolysed in passage in the intestinal mucosa and free cefuroxime enters the systemic circulation

Cephamycins - active against B.fragilis

excreted in urine, except for cefaclor these drugs are more stable to beta lactamases

Third generation

- highly augmented activity against gram megative Eterobacteriaceae and few members inhibit Psuedomonas

- highly resistant to beta lactamases

- less active against gram positive cocci and anaerobes

- some cross BBB

Cefotaxime- prototype

- indications - Meningitis, life threatening resistant/ hospital acquired ifnections, septicaemias and infections in immuno-compromised patients.

- alternative to ceftriaxone or typhoid

- used in Urethritis

2. Ceftazidime - high activity against P.aeruginosa

3 . Ceftriaxone - longest t1/2

4. Ceftuzoxime - good against B.fragilis

5. Cefoperazone - eliminated 70% in bile (useful in renal failure) and disulfiram like action is seen

Fourth generation cephalosporins

- more resistant to beta lactamases

- active against P.aeruginosa , Enterobacteriaceae

- Cefepime , cefpirome

Fifth generation

- active against MRSA and other bacteria

- Ceftaroline fosamil - i.v

- rapidly converted by phosphatases to the active ceftaroline

- high affinity for PBP2a (in MRSA), for PBP2b and PBP2x

- interferes with transpeptidation step of bacterial cell wall synthesis and exerts lethal effect.

- Adverse effects - headache, dizziness, itching, rashes, fever, diarrhoea, and irritation of the injected vein