Cepahlosporins

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