29.ppt
- 2. • Cephalosporin antibiotics –derived from “cephalosporin C” –obtained from fungus Cephalosporium acremonium • Cephalosporin nucleus Consists of dihydrothiazine ring fused to a β–lactam ring –7-aminocephalosporanic acid 2
- 3. • 7-aminocephalosporanic acid has been modified by addition of different side chains to create a whole family of cephalosporin antibiotics. • these have been conventionally divided into 5 generations 3
- 4. Mechanism of action • All cephalosporins are bactericidal. • MOA same as penicillin- Inhibit cell wall synthesis in a manner similar to penicillins • Bind to different proteins than those which bind penicillin. PBP-1 &PBP-3 – This explains diffenece in spectrum, potency & lack of resistance. 4
- 5. • Inhibition of transpeptidation • Imperfect cell wall • Osmotic drive • Activation of autolysin enzymes • Lysis of bacteria • BACTERICIDAL 5
- 6. CLASSIFICATION • Based on –antimicrobial spectrum –Chronological sequence of development –Divided into generations. 6
- 7. First-generation agents • Cephalexin (O) • Cefadroxil (O) • Cefazolin (i.m, i.v) • Cefalothin (withdrawn) 7
- 8. • Exhibit good activity against gram-positive bacteria but modest activity against gram negative organisms. – Most gram-positive cocci – Strepto, – Pneumo, – Methicillin sens. Staph. are susceptible to first-generation cephalosporins • Modest activity against E. coli, K. pneumoniae & Proteus mirabilis Most oral cavity anaerobes are sensitive. However, the Bacteroides fragilis group is resistant. 8
- 9. Second-generation agents –Cefaclor (O) –Ceforanide –Cefuroxime acetil (O) –Cefuroxime (i.m , i.v) –Cefoprozil –Cefamandole (Banned) –Cefoxitin (Banned) –Cefotetan (Banned) 9
- 10. • Exhibit somewhat increased activity against gram negative organisms, –but much less active than third generation agents. • Less active against gram positive cocci & bacilli compared to first gen. drugs. • Use declined • Clinically replaced by 3rd & 4th generation drugs . 10
- 11. Third-generation agents • Cefotaxime • Ceftriaxone • Cefdinir • Cefibuten • Cefpodoxime • Ceftizoxime • Ceftazidime • Cefoperazone (withdrawn) 11
- 12. • Highly augmented activity against gram-negative organisms • Less active than first generation agents against gram positive cocci & anaerobes. • All are highly resistant to β-lactamases from gram negative bacteria. • Some inhibit psuedomonas as well; ceftazidime, cefoperazone(withdrawn) 12
- 13. • Some members of this group have enhanced ability to cross the blood-brain barrier eg. Ceftriaxone and are effective in treating meningitis caused by pneumococci, meningococci, H. influenzae and susceptible gram negative rods. 13
- 14. Fourth-generation agents • Cefpirome P/E (im/iv) • Cefepime P/E (iv) • Cefozopran P/E 14
- 15. • Highly active against G –ve organisms • Similar to third gen drugs for g +ve bacteria • The fourth generation drugs comparable to third generation but more resistant to hydrolysis by β-lactamases. – Effective against bacterial infections resistant to earlier drugs 15
- 16. Fifth-generation agents • Ceftobiprole • Ceftaroline • Active against, g +ve cocci especially MRSA • penicillin resistant S. pneumoniae • and enterococci 16
- 17. Resistance • Impermeability to the antibiotic. – to reach its site of action • Alteration in PBPs -antibiotics bind with low affinity • Elaboration of β-lactamases; that can hydrolyze the β-lactam ring and inactivate the cephalosporin (most prevalent mech) 17
- 18. Adverse reactions • Pain after im injection • Thrombophlebitis of injected vein. • Diarrhoea more common with – oral Ceferadine – P/E Cefoperazone (Banned) 18
- 19. • Hypersensitivity reactions – Identical to penicillins, incidence is lower. – shared β-lactam structure – Allergic to penicillins- allergic to cephalosporins. CROSS- REACTIVITY. • Rashes, frequent, anaphylaxis, angioedema, asthma, urticaria have also occurred. 19
- 20. • Cephalosporins potentially nephrotoxic drugs –Cephaloridine (withdrawn) RTN –Cephalothin (withdrawn) Acute tubular necrosis • Serious bleeding –Cefoperazone(Banned), –Moxalactam(Banned). –Due to hypoprothrombinemia. 20
- 21. • Intolerance to alcohol Disulfiram like reaction – Cefamandole (Banned) – Cefotetan (Banned) – Moxalactam (Banned) – Cefoperazone (Banned) 21
- 22. Therapeutic Uses • Extensively used & therapeutically important antibiotics • Effective therapeutic & prophylactic agents 22
- 23. First Gen agents • Excellent for skin & soft tissue infections • Surgical prophylaxis first generation drugs are the preferred for prophylaxis in procedures in which skin flora are likely pathogens. 23
- 24. Second Gen agents • Displaced by third generation agents for Gram negative infections • Oral-RTI (replaced by augmentin) 24
- 25. Third Gen agents • With/without aminoglycosides DOC- severe G -ve infections caused by • Kleibsiella • Enterobacter • Proteus • Providencia • Serratia & haemophillus species. 25
- 26. • Ceftriaxone is the therapy of choice for all forms of Gonorrhea – 250 mg i.m as single dose • i.v ceftriaxone for enteric fever • Cefotaxime & ceftriaxone –Community aquired pneumonia 26
- 27. • Cefotaxime/ceftriaxone are used for initial treatment of meningitis because of their – antimicrobial activity, – good penetration into CSF – & record of clinical success • They are DOC - Meningitis due to • H. influenzae • Sensitive S. pneumonae • N. meningitidis • G-ve enteric bacteria • Ceftazidime + aminoglycosides –Psuedomonas meningitis DOC 27
- 28. Fourth Generation Agents • Same as third generation drugs • Indicated for hospital acquired infections resistant to commonly used antibiotics 28
- 29. • Other β -lactam antibiotics 29
- 30. Other β -lactam antibiotics • Newer classes of β-lactam antibiotics are the •Monobactams •Carbapenems •Carbacephems • Important therapeutic agents with a β-lactam structure & are neither penicillins nor cephalosporins 30
- 31. Monobactams Aztreonam • Isolated from chromobacterium violaceum – Only monobactam currently in clinical use • β - lactam ring, lacking the thiazolidine ring. - a monobactam 31
- 32. • Antimicrobial activity differs from those of other β - lactam antibiotics & more closely resembles that of an aminoglycoside • Primarily affects : – Aerobic gram negative microorganisms – gram positive bacteria & anaerobic organisms are resistant • Preferred-all sorts of gram negative infections in patients with renal impairment where aminoglycosides are to be avoided. 32
- 33. • Stable to most β-lactamases elaborated by gram negative bacteria. • i.m / i.v • Therapeutic conc. in CSF in the presence of inflammed meninges, Alternative to cephalosporins for therapy of meningitis caused by G-ve bacilli 33
- 34. Carbapenems • β-lactam antibiotic • Broader spectrum of activity : than most other β- lactams . –gram-negative rods –gram-positive bacteria –and anaerobes. 34
- 35. Carbapenems • Imipenem • Meropenem • Ertapenem 35
- 36. Imipenem • Derived from compound produced by Streptomyces cattleya • Mechanism same as penicillins • Bactericidal • Resistant to hydrolysis by β-lactamase • Marketed in combination with cilastin – Inhibits degradation – by renal dipeptidase – Without cilastin renal dehydropeptidases inactivate the drug which results in low urinary tract concentrations. 36
- 37. Adverse effects • Nausea ,vomiting • Seizures • Patients allergic to other β-lactam antibiotics may have hypersenstivity reactions when given imipenem 37
- 38. Meropenem • Therapeutic equivalence with imipenem • Coadministration with cilastin not required • Meropenem is less seizure producing compared to imipenem. 38
- 39. Ertapenem • Differs from imipenam & meropenem larger serum half life, OD. – Co-administration with cilastin not required – less seizure producing compared to imipenem. 39
- 40. • All are parenteral – i.v, im painful • Imipenem 6 hrly • Meropenam 8 hrly • All are resistant to β – lactamases • All bactericidal • MOA same • Patients allergic to other β-lactam antibiotics may have hypersenstivity reactions when given imipenem/carbapenems. 40
- 41. Therapeutic uses • Urinary tract infections • Lower respiratory tract infections • Intra-abdominal & gynaecological infections • Skin, bone, joint, & soft tissue infections • Especially cephalosporin/ penicillin resistant nosocomial bacteria. 41
- 42. Carbacephems Loracarbef • Synthetic β-lactam antibiotic • Similar to cefaclor • Antibacterial activity resembles II generation cephalosporins. 42
- 43. THANK U 43