cephalosporins

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cephalosporins

  1. 2. <ul><li>These are substance produced by micro-organisms or synthetic compounds, which suppress the growth or kill other micro-organisms. </li></ul><ul><li>Selman Walksman </li></ul><ul><li>1942 </li></ul>
  2. 3.
  3. 4. <ul><li>These are a group of semi synthetic antibiotics derived from ‘Cephalosporin-C’ obtained from a fungus Cephalosporium acremonium. </li></ul><ul><li>Mechanism of action : </li></ul><ul><li>Cephalosporins are bactericidal and have the same mode of action as other beta-lactam antibiotics (such as penicillin). </li></ul><ul><li>Cephalosporins disrupt the synthesis of the peptidoglycan layer of bacterial cell walls. </li></ul><ul><li>The peptidoglycan layer is important for cell wall structural integrity. </li></ul>
  4. 5. <ul><li>It is active against both Gram-positive and Gram-negative organisms. </li></ul><ul><li>Classification: </li></ul><ul><li>These has been conventionally classified into four generations. </li></ul><ul><li>This is based on chronological sequence of development, but more importantly ,takes into consideration the overall antibacterial spectrum as well as potency. </li></ul><ul><li>First-generation cephalosporins are predominantly active against Gram-positive bacteria, and successive generations have increased activity against Gram-negative bacteria (albeit often with reduced activity against Gram-positive organisms). </li></ul>
  5. 6. <ul><li>Developed in 1960, active against Gm+ weaker on Gm- orgnisms. </li></ul><ul><li>Cephalothin: 1 st cephalosporin used. (Parenteral) </li></ul><ul><li>active against: Streptococci, Staphylococci, gonococci, meningococci, C.diptheriae and clostridia. </li></ul><ul><li>Cephalexin: Orally active. commonly used. (SPORIDEX) </li></ul><ul><li>Cefadroxil: Excellent tissue penetration (cefadrox) </li></ul><ul><li>Excreted unchanged in urine. </li></ul><ul><li>Dose adjustment in renal impaired patients. </li></ul><ul><li>Cephazolin: Active against klebsiella and E.coli. (Parenteral) </li></ul><ul><li>Preferred parenteral 1 st gen cephalosporin for surgical prophylaxis (ALCIZONE/ORIZOLIN) </li></ul>
  6. 7. <ul><li>Cefuroxime: Resistant to Gm- beta lactamase (Parenteral) </li></ul><ul><li>Important use: meningitis caused by H. influenzae, </li></ul><ul><li> meningococci, pneumococci. (SUPRACEF) </li></ul><ul><li> Single dose i.m therapy for gonorhoea. </li></ul><ul><li>Cefuroxime axetil: Ester of cefuroxime, effective orally. </li></ul><ul><li>Uses: URTI, LRTI, UTI, skin and soft tissue infection </li></ul><ul><li>group B streptococci,salmonella, E.coli </li></ul><ul><li>(CEFTUM,ZOCEF ) </li></ul>
  7. 8. Third generation <ul><li>Broad-spectrum. </li></ul><ul><li>Active against Gm- enterobacteriacae. </li></ul><ul><li>Some are anti-pseudomal. </li></ul><ul><li>Resistant to beta-lactamase . </li></ul><ul><li>Cefotaxim: (TAXIM/OMNATAX) </li></ul><ul><li>Prototype of third generation cephalosporin. </li></ul><ul><li>Widely distributed in body tissues and fluids, penetrates CSF best when meninges are inflamed. </li></ul><ul><li>Uses: Aerobic Gm- bacteria infection, poor on anaerobes (B. fragilis), Staphylococci and pseudomonas. </li></ul><ul><li>prominent indications: meningitis </li></ul><ul><li>life-threatening nosocomial infection </li></ul><ul><li>septicaemia </li></ul><ul><li>infection in immunocompromised patients. </li></ul>
  8. 9. Ceftriaxone: <ul><li>Longer duration of action. ( MONOCEF/CEFERA ) </li></ul><ul><li>Good CSF penetration. </li></ul><ul><li>USES: Bacterial meningitis </li></ul><ul><li>Multi-Resistant typhoid fever </li></ul><ul><li>Complicated UTI </li></ul><ul><li>Abdominal sepsis and septicaemia </li></ul><ul><li>Specific Adverse effect: Hypoprothrombinaemia and bleeding </li></ul><ul><li>Ceftazidime: (CEFZID/TAZID) </li></ul><ul><li>Active against pseudomonas. </li></ul><ul><li>Specifically used in febrile neutropenic patients with haematological malignancies </li></ul><ul><li>Burn. </li></ul>
  9. 10. <ul><li>Cefoperazone: (CEFOMYCIN/NOVACIP) </li></ul><ul><li>Strong anti-pseudomonal property. </li></ul><ul><li>Cidal against S.typhi, B.fragilis. </li></ul><ul><li>More susceptible to beta-lactamase. </li></ul><ul><li>USES: severe urinary, biliary, respiratory, skin-soft tissue infection, meningitis and septicaemia. </li></ul><ul><li>Cefixime: (ORIFIX/TAXIM-O/OMNATAX) </li></ul><ul><li>Orally active 3 rd generation </li></ul><ul><li>Broad spectrum of action- enterobacteriaceae, H. influenzae, Strep pyogenes. Not active against Staph and Pseudomonas . </li></ul><ul><li>Cefpodoxim proxetil. (CEPODEM) </li></ul><ul><li>Orally active 3 rd generation </li></ul><ul><li>Active against enterobacteriaceae and streptococci. </li></ul><ul><li>Excellent outcome in RTI, UTI and soft-tissue infection. </li></ul><ul><li>Cefdinir: (SEFDIN/ADCEF) </li></ul><ul><li>Orally active </li></ul><ul><li>Excellent results in pneumonia,COPD,ENT & skin infections. </li></ul>
  10. 11. <ul><li>Fourth generation: </li></ul><ul><li>Cefepime: (CEPIME/MEGAPIME) </li></ul><ul><li>Highly resistant to beta-lactamase. </li></ul><ul><li>Active against pseudomonas and Staph besides host of organisms </li></ul><ul><li>Uses: Serious life-threatening hospital acquired pneumonia </li></ul><ul><li>Febrile neutropenia. </li></ul><ul><li>Bacterremia and septicaemia. </li></ul><ul><li>Cefpirome: (CEFROM/CEFORTH) </li></ul><ul><li>Treatment of serious and resistant hospital acquired infections including septicaemia ,pneumonia . </li></ul><ul><li>Covers some Gm+ organisms as well. </li></ul>
  11. 12. <ul><li>Adverse effects: </li></ul><ul><li>Pain at the site of I.M injection. </li></ul><ul><li>Thrombophlebitis on I.V injection . </li></ul><ul><li>Diarrhoea- d/t alteration of gut ecology or irritant effect of drug. </li></ul><ul><li>Hypersensitivity reaction- Rashes, anaphylaxis, urticaria, asthma. </li></ul><ul><li>10% patients allergic to penicillin shows cross-reactivity. </li></ul><ul><li>Nephrotoxicity- cephaloridine (withdrawn) </li></ul><ul><li>Accentuated by pre-existing renal disease, concurrent amino glycosides,loop diuretics </li></ul><ul><li>Bleeding- cefoperazone,ceftriaxone. Warfarin like action. </li></ul><ul><li>common in patients with cancer, Intra-abdominal infections </li></ul>

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