Cephalosporins

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Cephalosporins

  1. 1.  Derivatives of 7-amino-cephalosporanic acid  Cephamycins are fermented products of streptomyces  Closely related in structure to penicillin (beta- lactam ring).  They are highly resistant to penicillinase.  Some bacteria can produce a beta lactamase called cephalosporinase  Many of them are resistant to the enzyme.
  2. 2. 4 Monobactams All of the drugs in this group contain a β-lactam ring in their structure Penicillins N O S Carbapenems N O N O N O S Cephalosporins share similar • features of chemistry, • mechanism of action, • pharmacologic and clinical effects.
  3. 3.  Cephalosporins inhibit the peptido-glycan synthesis of bacterial cell wall in a manner similar to that of penicillin and are considered bactericidal.
  4. 4. 6
  5. 5.  Divided into 4 major groups called “Generations”  Are divided into Generations based on  Parallel their chronological development  Their antimicrobial spectrum › First generation › Second generation › Third generation › Fourth generation
  6. 6. EXAMPLES: Cephalothin, Cefazolin, Cephalexin , Cephadroxil They have a stronger antimicrobial action on G+ bacteria than that of the other generations, but they action on G- bacteria is relatively poor. ① These cephalosporins have nephrotoxicity to a certain degree. ② They are NOT effective against pseudomonas. First Generation Cephalosporins
  7. 7. ④ Comparatively, they are less stable for beta- lactamase (penicillinase ). ⑤ They are chiefly used in treating infection of the penicillinase-producing S.aureus and for surgical prophylaxis. ⑥ Cefazolin do not penetrate the central nervous system and can not be used to treat meningitis. First Generation Cephalosporins
  8. 8.  Treatment infection of the penicillinase- productive S.aureus  Minor staphylococcal lesions  For surgical prophylaxis  Cephazolin drug of choice for k. pneumonie infections  Treatment of staphylococcal or streptococcal infection who have a h/o penicillin hypersensitivity. 10
  9. 9.  Cefamandole, Cefaclor, Cefuroxime, Cefot etan, Cefoxitin (Cephamycins) ① Action of this generation on G+ bacteria is the same or a little less than that of the first generation. ② Their antimicrobial action on G- bacteria is obviously increased. (H. influenza, Klebsiella) ③ Cephamycins are effective against anaerobes such as B.fragilis, serratia
  10. 10. ④ Ineffective against p.aeruginosa. ⑤ They are stable to many kind of beta- lactamases and have less nephrotoxicity than the first generation. ⑥ Cefuroxime is the only second- generation drug that crosses the blood- brain barrier : used for the treatment of meningitis, especially H.influenzae meningitis, and sepsis.
  11. 11.  Sinusitis, Otitis, LRTI, Community acquired pneumonia › caused by beta lactamase producing H. influenza  Meningitis  Mixed infections : › Peritonitis › Diverticulitis › pelvic infections 13
  12. 12.  Cefotaxime, Ceftriaxone, Cefoperazone, Cefixime, Ceftizidime, Cefodoxime. ① The broadest spectrums of all cephalo- ② The highest activities against G- bacteria. ③ The lowest activities against G+ bacteria. ④ The highest resistance to β-lactamase. ⑤ Can cross blood brain barrier
  13. 13. ⑤ The best penetration into the CSF; almost no nephrotoxicity. ⑥ Ceftizoxime have good activity against B.fragilis. ⑦ Some of them are effective against P.aeruginosa and enteric bacilli. (cefoperazone and ceftizidime)
  14. 14.  There are also some unique properties of individual 3th generation.  Ceftriaxone has the longest half-life(8h) of any cephalosporin.  Cefixime is an oral preparation.  Ceftazidime is the best anti-pseudomonal cephalosporin.  Cefoperazone is eliminated(70%) in the bile, and is thus very useful in patients with renal failure.
  15. 15.  Used for serious infections caused by organisms resistant to other drugs.  Gonorrhea : cefixime / ceftriaxone  Meningitis : Ceftriaxone, cefotaxime  community acquired pneumonia: Ceftriaxone  Septicemia  Nosocomial infections  UTI  LRTI  Soft tissue infections  cellulitis  Typhoid fever  Mixed aerobic , anaerobic infections  Urethral , biliary tract infections
  16. 16.  First line drug for Gonorrhea caused by Nisseria (ceftriaxone , Cefixime)  Meningitis caused by pneumococci, meningococci, H. influenza.  Empirical theraphy for sepsis of unknown cause  Urethral or biliary tract infections 18
  17. 17. Cefepime 1. More resistant to hydrolysis by β- lactamase 2. Active against P-aeruginosa & Enterobacteriaceace. 3. Clinical use as third generations.
  18. 18. Generations First second Third Drugs Cephalexin (O) Cefadroxil (O) Cefazolin (im, iv) Cephalothin (o,im) Cefaclor (o) Cefuroxime (o) Cefoxatin (im, iv) Cefotetan (im) Cefixime (o) Ceftriaxone (o) Cefotaxime (im, iv) Cefoperazone Antibacterial spectrum G+Ve +++ ++ + G -ve + ++ +++ Anaerobes Efective against B.Fragalis Very effective (cefotetan & cefoxitin) Effective (Cefoperazone) Pseudomonas - - -- effective Salmonella -- - effective Betalactamase Resistant to staphylococcal H, resistant to G- ve Highly resistant BBB --- Only cefuroxime Most drugs
  19. 19.  Relatively few and low  The most common ones are Allergy- hypersensitivity reactions (5%-10%) anaphylaxis, fever, skin rashes, nephritis, granulocytopenia, and hemolytic anemia.  During treatment with third-generation drugs, these resistant bacteria, as well as fungi, often proliferate and may induce superinfections.
  20. 20.  Nephrotoxicity:  The first-generation cephalosporins have certain nephrotoxicity. (Renal damage, including interstitial nephritis and even tubular necrosis )  The second-generation have slight nephrotoxicity.  The third-generation have no nephrotoxicity.
  21. 21. Monobactams - Aztreonam ① Aztreonam is highly resistant to beta- lactamases ② It is highly active against aerobic G- bacteria, including P.aeruginosa and penicillinase- producing strains of H. influenzae and gonococci. But it shows poor activity against G+ cocci and anaerobic bacteria. ③ The antimicrobial spectrum of aztreonam is similar to that of aminoglycosides
  22. 22.  Mechanism of action  Pharmacologic effects  Clinical Uses  Adverse Effects Vancomycin Vancomycin is an antibiotic produced by Streptococcus orientalis.
  23. 23. ① Vancomycin is very effective against most staphylococci including those producing beta-lactamases,and other G+ cocci such as streptococcus viridans, enterococci, and pneumococcus. ② It is also active against clostridium species, Corynebacterium diphtheriae, and Bacillus anthracis.
  24. 24. ① Orally only for the treatment of antibiotic- associated Pseudomembranous colitis caused by C.difficile. ② Intravenous administration is mainly used for serious G+ coccal infections, such as enterocolitis, septicemia › Especially for those caused by penicilin- resistant pneumococcus and staphylococci
  25. 25. ① Phlebitis › at the site of injection. ② Nephrotoxicity and Ototoxicity › rare with monotherapy, more common when administered with other nephro- or ototoxins › risk factors include renal impairment, prolonged therapy, high doses, high serum concentrations, other toxic meds
  26. 26. ③ “Red-Man”or “red neck” Syndrome › flushing, pruritus, erythematous rash on face and upper torso › related to RATE of intravenous infusion; should be infused over at least 60 minutes › resolves spontaneously after discontinuation › Prevent: may lengthen infusion (over 2 to 3 hours) or pretreat with antihistamines in some cases
  27. 27.  They are available only in fixed combinations with specific penicillins:  Ampicillin + sulbactam  Amoxicillin + clavulanic acid  Ticarcillin + clavulanate potassium  Piperacillin + tazobactam sodium
  28. 28.  (Amp/Sulbactam)  Spectrum: Amp + most anaerobes + many enteric G (-) rods, OSSA  Sulbactam alone is very active against Acinetobacter spp. 30
  29. 29.  (Pip/Tazo)  THE most broad-spectrum penicillin  Tazobactam may improve the activity of piperacillin vs. gram-negative rods, including anaerobes  4.5g IV q8h = 3.375g IV q6h  4.5g IV q6h for Pseudomonas 31

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