Lec2

• Monobactams

  • Aztreonam
• Cephalosporins 3rd generation

  • Cefixime
  • Ceftriaxone
  • Cefotaxime
• Cephalosporins 2nd generation

  • Cefaclor
  • Cefoxitin
  • Cefuroxime
• Cephalosporins 4th generation

  • Cefepime
• Penicillin is among the most widely effective antibiotics and among the least toxic drugs known. It is bactericidal.
• Carbapenems

  • Imipenem
  • Meropenem
  • Ertapenem
• Cephalosporins 1st generation

  • Cefazolin
  • Cefadroxil
  • Cephalexin
• Mechanism of action of Penicillin

  1. Penicillin interacts with penicillin binding protein (PBP) on the cytoplasmic membrane to inhibit transpeptidation reactions involved in cross-linking of peptidoglycan chains, the final step in cell wall synthesis

  2. Activation of autolytic enzymes (autolysins) stored inside bacteria
• Penicillins are only effective against rapidly growing organisms that synthesize a peptidoglycan cell wall. Consequently, they are inactive against organisms devoid of this structure, such as mycobacteria, protozoa, fungi, viruses, and Gram-negative bacteria
• Penicillins

  • Penicillin G
  • Penicillin V
  • Methicillin
  • Nafcillin
  • Oxacillin
  • Cloxacillin
  • Ampicillin
  • Amoxycillin
  • Carbenicillin
  • Ticarcillin
  • Pipercillin
  • Azlocillin
• The penicillin nucleus itself is the chief structural requirement for biological activity; Metabolic transformation or chemical alteration of this portion of the molecule causes loss of all significant antibacterial activity
• ampicillin and amoxycillin works on :

  • Gram-positive cocci (not staph), E. coli, H. influenza, Listeria monocytogenes
• Subgroups and Antimicrobial Activity of Beta-lactam Antibiotics: Antistaphylococcal

  • Very Narrow spectrum, β-lactamase resistant: Nafcillin, Methicillin, Cloxacillin
• Spectrum of Natural Penicillin

  • Streptococcal infection (Pharyngitis, Otitis media, Rheumatic fever), Pneumococcal infection, Meningococcal infection like meningitis, Gonorrhea, Gram-positive bacilli like B. Anthracis, C. Diphtheriae, All clostridia are highly sensitive, so are Spirochetes
• Spectrum of Others β-lactamase sensitive Anti Pseudomonal Antibiotics

  • Gram-negative rods including Pseudomonas
• Subgroups and Antimicrobial Activity of Beta-lactam Antibiotics: Extended spectrum

  • β-lactamase sensitive: ampicillin and amoxicillin
• Subgroups and Antimicrobial Activity of Beta-lactam Antibiotics: Natural Penicillin

  • Narrow spectrum, β-lactamase sensitive: Penicillin G (natural penicillins) Acid labile, Penicillin V (acid stable)
• Organisms that synthesize a peptidoglycan cell wall

  • Consequently they are inactive against organisms devoid of this structure, such as mycobacteria, protozoa, fungi, viruses, and Gram-negative bacteria
• Others β-lactamase sensitive Anti Pseudomonal Antibiotics

  • Ticarcillin, piperacillin, azlocillin
• Beta-lactamase inhibitors


  • Clavulanic acid, sulbactam, Tazobactam
• PHRS – 303 LECTURE 2: Beta lactam Antibiotics: Penicillin Dr. Rawan Alnafisah


  3 Mar. 2024
• Activation of autolytic enzymes(autolysins)


  These group of enzymes are stored inside bacteria. Once they are released, they are activated and destroy the existing cell wall
• Spectrum of Antistaphylococcal Antibiotics

  • Known or suspected staphylococci
• lactam Antibiotics include:

  penicillin , cephalosporins , carbapenems , monobactam
• Mechanisms of Resistance to Beta-lactam Antibiotics
• Production of beta-lactamase by the organism

  Breaks down penicillin into penicillonic acid, which has no antibacterial activity
• Structural change in PBPs

  Occurs in methicillin-resistant S. aureus and penicillin-resistant pneumococci
• Pharmacokinetics of Penicillin
• Administration of Penicillin

  Depends on the type: oral (amoxicillin), IV (methicillin, ticarcillin, carbenicillin, piperacillin), or IM route (procaine penicillin and benzathine penicillin)
• Absorption of Penicillin


  Most penicillins are incompletely absorbed after oral administration and reach the intestine in sufficient amount to affect the composition of the intestinal flora
• Distribution of Penicillin

  Good distribution throughout the body, does not cross the blood-brain barrier except in meningitis when the BBB becomes leaky, can cross the placenta but is not teratogenic as there is no target in the fetus
• Metabolism of Penicillin

  Usually insignificant, but some metabolism of penicillin G has been shown to occur in patients with impaired renal function
• Excretion of Penicillin


  Most are eliminated through active tubular secretion, nafcillin is eliminated largely in bile
• Plasma half-life of penicillin is usually less than 2 hours
• Benzylpenicillin (penicillin G) has the following properties:
• Benzylpenicillin (penicillin G) properties

  • Narrow spectrum
  • Bactericidal in action and very high activity
  • Destroyed by gastric HCL
  • Destroyed by beta-lactamase
  • Short duration of action
  • Highly water soluble
• Benzylpenicillin (penicillin G) indications

  • Pneumococcal, streptococcal (infective endocarditis), meningococcal meningitis, tetanus, gas gangrene, Tryponema, syphillis, Gonococci (gonorrhoea)
• Penicillin G is calculated by units. Each mg contains 1600 units per mg, 1 million units = 0.6 g
• In dry form, penicillins are stable for years at 4 °C. Solutions lose their activity rapidly (24 hours at 20 °C) and must be prepared fresh
• Disadvantages of Penicillin G include short duration of action, beta-lactamase sensitivity, narrow spectrum, and being destroyed by gastric acid (acid labile)