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Beta Lactam Antibiotics- Cephalosporins��

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Faculty of Pharmacy

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Beta Lactam Antibiotics- Cephalosporins��

At the end of this lecture, the student will be able to:

  • Describe the antimicrobial spectrum of cephalosporins
  • Explain the mechanism of action of caphalosporins
  • Discuss the pharmacokinetics and adverse effects of cephalosporins

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Contents

Cephalosporins

  • Mechanism of action
  • Classification
  • Pharmacokinetics
  • Adverse effects
  • Clinical uses

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Cephalosporins

  • Cephalosporins chemical analogues – cefamycins
  • Dihydrothiazine ring fused to β-Lactam ring with an appropriate side chain on position-7
  • Isolated from Cephalosporinium acremonium and Streptomyces lactamdurans

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Structure of Cephalosporins

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Structure of Penicillin vs Cephalosporins

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Mechanism of Action of Cephalosporins

  • Identical to penicillin
  • Inhibition of transpeptidation
  • Formation of imperfect cell wall
  • Osmotic changes
  • Activation of autolysin enzyme
  • Lysis of bacteria – Bactericidal

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Classification and Antimicrobial Spectrum

  • According to their ‘generation’ and antibacterial spectrum, stability to β-Lactamase and year of production
  • First generation – 1960s
  • Second generation – 1970s
  • Third generation – 1980s
  • Fourth generation – 1997-1998
  • Fifth Generation- 2000-

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First Generation Cephalosporins

  • Cephalexin, Cephapirin, Cefadroxil – Oral
  • Cephradine – oral & parenteral
  • Cephalothin & cefazolin – parenteral
  • β-Lactamase sensitive
  • Oral drugs- well absorbed from GIT
  • High serum level than tissues
  • Metabolism not significant
  • Excreted through urine

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First Generation Cephalosporins

Antimicrobial spectrum

  • Sensitivity against gram positive cocci
  • Gram negative bacteria like E. coli, K. pneumoniea, Proteus mirabilis
  • Anaerobic cocci sensitive are – peptococcus and peptostreptococcus

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First Generation Cephalosporins

Clinical uses

  • UTI, minor staphylococcus infections
  • Cefazolin – surgical prophylaxis before cardiac surgery, orthopaedic prosthesis procedures
  • Ineffective in meningitis
  • As an alternative to penicillins

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Second Generation Cephalosporins

  • Cefaclor, Cefmetazole, Cefprozil – Oral
  • Cefoxitin Cefamandol, cefotetan – parenteral
  • Cefuroxime – oral or parenteral

Antimicrobial spectrum

  • Extended spectrum against gram negative organisms

K. Pneumonia

H. influenza

Bacteriodis fragilis

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Second Generation Cephalosporins

Pharmacokinetics

  • Well absorbed from GIT
  • Resistance to β- lactamase – except cefaclor
  • Protein binding is significant
  • Cefuroxime – cross BBB
  • Excreted unchanged in urine

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Second Generation Cephalosporins

Clinical uses

  • Sinusitis
  • Otitis
  • Lower respiratory tract infection
  • Effective against anerobes – peritonitis & diverticulitis
  • Cefuroxime – community acquired pneumonia

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Third Generation Cephalosporins

Oral drugs

Parenteral drugs

Cefixime

Cefotaxime

Cefpodoxime

Cefitzoxime

Cefdinir

Ceftriaxone

Ceftibuten

Ceftazidime

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Cefoperazone

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Third Generation Cephalosporins

Advantages

  • Extended spectrum gram negative
  • Effective against β-lactamase producing haemophillus and nesseria
  • All can cross BBB

Disadvantage

  • Sensitive to constitutively produced β-lactamase in organisms like enterobacter

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Third Generation Cephalosporins

Pharmcokinetics

  • Oral – good bioavailability
  • Given i.v with anesthetic
  • Distribution is good – except cefoperazone
  • Reaches good level in CNS

Uses – Gonorrhae, meningitis and sepsis

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Fourth Generation Cephalosporins

  • Cefipime
  • Cefpirome
  • Cefozoram
  • Extended gram negative coverage
  • Resistance to β-lactamase
  • Used in gonorrhae, meningitis and sepsis

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Fourth Generation Cephalosporins

Adverse effects

  • Super infection
  • Pain when injected IM
  • Thrombophlebitis may occur after i.v
  • Allergic reaction
  • Renal toxicity
  • Interstitial nephritis
  • Bleeding disorders and fall in prothrombin time

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Fifth Generation Cephalosporins

  • Ceftobiprole and Ceftaroline
  • Inhibit cell wall synthesis
  • Inhibit penicillin binding protein 2a produced by MRSA and penicillin resistant S. pneumoniae
  • Super infection, coagulation abnormalities and pseudolithiasis

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Summary

  • Cephalosporins and their chemical analogues – cefamycins consists of dihydrithiazine ring fused to β-Lactam ring with an appropriate side chain on position-7
  • Isolated from Cephalosporinium acremonium and Streptomyces lactamdurans
  • Mechanism of action is similar to that of penicillins
  • Anti Microbial spectrum-First generation cephalosporins: Sensitivity against gram positive cocci; Gram negative bacteria like E. coli, K. pneumoniea, Proteus mirabilis; Anaerobic cocci sensitive are – peptococcus and peptostreptococcus
  • Second generation cephalosporins: Extended spectrum against gram negative organisms- K. Pneumonia, H. influenza, Bacteriodis fragilis
  • Third and fourth generation cephalosporins: Gonorrhae, meningitis and sepsis

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Faculty of Pharmacy