antibacterial

• Antibacterial


  Substance that inhibits the growth or destroys microorganisms
• Antibiotics


  Substance produced by microorganisms that inhibits the growth or destroys other microorganisms
• Historical background


  • Sir Alexander Fleming accidentally discovered the antibacterial properties of penicillin from Penicillium notatum in 1929
  • Florey & Chain purify penicillin and introduced it into therapy
  • Pasteur & Joubert discovered the anthrax bacilli
• Antibiotic


  A substance produced by microorganisms, which has the capacity of inhibiting the growth and even of destroying other microorganisms (Waksman, 1942)
• Requirements for antibiotics


  • It is a product of metabolism (although it may be duplicated or even have been anticipated by chemical synthesis)
  • It is a synthetic product produced as a structural analog of a naturally occurring antibiotic
  • It antagonizes the growth or survival of one or more species of microorganisms
  • It is effective in low concentrations
• β-Lactam antibiotics


  • Penicillins
  • Cephalosporins
• Mechanism of action


  Interfere with the last step of bacterial cell wall synthesis (transpeptidation or cross-linking of peptidoglycan chains)
• Penicillins


  • Beta-lactam attached to thiazolidine ring
  • Nucleus: 6-aminopenicillanic acid
• Bacterial resistance


  Penicillinases (β-lactamases) - enzymes that catalyze the hydrolytic opening of the β-lactam ring of penicillins to produce inactive penicilloic acid (S. aureus and most gram-negative bacteria)
• Spectrum of activity


  • Effective against gram-positive, spirochetes and anaerobe bacteria
  • Some gram-negative bacteria and mycoplasma are resistant

  
• Adverse effect


  Hypersensitivity (variety of skin and mucous membrane rashes to a drug fever and anaphylaxis)
• Natural penicillins


  • Penicillin G (Benzylpenicillin)
  • Given IV/IM
  • Made available in the form of water-soluble salt of potassium, sodium and calcium
  • Poorly absorbed from the intestinal tract, oral doses must be very large
  • Its rapid elimination from the bloodstream led to the development of repository forms
  • Repository forms (IM): Pen G Benzathine, Pen G Procaine
  • DOC for many bacterial infections (Ex: Rheumatic Heart Disease in children and Syphilis)
• Penicillin G Procaine


  • Crysticillin®, Duracillin®, Wycillin®
  • Mixture of penicillin with procaine HCl
• Penicillin G Benzathine


  • Bicillin®, Permapen®
  • Gives the compound great stability and prolonged duration of action
• Penicillin V


  • Phenoxymethylpenicillin
  • Pen Vee®, V-Cillin®
  • Acid stable thus used orally
• Penicillinase-resistant penicillins/Antistaphylococcal penicillins


  Narrow spectrum
• Methicillin


  • 2,6-dimethoxyphenylpenicillin
  • Staphcillin®
  • Off the market due to high incidence of interstitial nephritis
  • Absence of the benzyl methylene group of penicillin G and the steric protection by the 2- and 6-methoxy groups makes it resistant to penicillinase
• Nafcillin


  • 6-(2-ethoxy-1-naphthyl)penicillin sodium
  • Unipen®
  • Acid stable enough to be used orally
  • Relatively small amounts are excreted through kidneys, with the major portion excreted in the bile
  • Can be given to patients with renal problem
• Isoxazoyl penicillins


  • Oxacillin
  • Cloxacillin
  • Dicloxacillin
• Oxacillin


  • Prostaphlin®
  • Resistant to acid hydrolysis thus administered orally
• Cloxacillin


  • Tegopen®
  • Resembles oxacillin but oral absorption is more enhanced
• Dicloxacillin


  • Dynapen®, Pathocil®, Veracillin®
  • Similar to cloxacillin
  • Enhanced stability
• Aminopenicillins


  Have an antibacterial spectrum similar to that of Pen G but are more effective against gram-negative bacilli
• Ampicillin


  • Penbritn®, Polycillin®, Omnipen®, Amcill®, Principen®
  • Poor GI absorption
  • More frequently administered parenterally
  • Not resistant to penicillinase
  • Used in UTI caused by E.coli or P.mirabilis
  • DOC for Haemophilus influenzae infection
  • Ampicillin + Probenecid = DOC for gonorrhea
  • Oral dose should be repeated every 6 hours because its is excreted rapidly and unchanged through the kidneys
• Prodrugs of ampicillin


  • Bacampicillin
  • Cyclacillin
  • Hetacillin
• Bacampicillin


  • Spectrobid®
  • Has no antibacterial property
  • Hydrolyzed rapidly by esterases in the plasma to form ampicillin
• Amoxicillin


  • Amoxil®, Larotid®, Polymox®
  • Better GI absorption than ampicillin
  • Resistant to acid but not with penicillinases
• Antipseudomonal penicillins/Extended spectrum


  • Carboxypenicillins
  • Ticarcillin
• Carbenicillin disodium


  • Geopen®, Pyopen®
  • Broader range of antimicrobial activity than any other known penicillin
  • Not stable in acid and penicillinase
  • Can be used for infections caused by gram-negative bacteria
• Carbenicillin indanyl sodium


  • Geocillin®
  • Provides orally active alternative for the treatment of carbenicillin-sensitive systemic and urinary tract infections caused by Pseudomonas spp, indole-positive Proteus spp., and selected Gram-negative bacilli
• Ticarcillin


  • Ticar®
  • Unstable in acid thus administered parenterally
• Ureidopenicillins


  • Piperacillin - most potent
  • Azlocillin
  • Mezlocillin
• Mezlocillin


  • Mezlin®
  • Recommended for the treatment of serious infections caused by Klebsiella spp., P. aeruginosa, H. influenzae and anaerobic bacteria
  • Unstable in acid and penicillinases
• Antibacterial


  Substance that inhibits the growth or destroys microorganisms
• Piperacillin


  • Pipracil®
  • Most active against gram-negative bacteria
  • Destroyed rapidly by stomach acid, give IV or IM
• Antibiotics


  Substance produced by microorganisms that inhibits the growth or destroys other microorganisms
• β-Lactamase inhibitors


  • Structurally related to beta-lactam ring of penicillin
  • Do not have significant antibacterial activity
  • Mechanism of action: Binds to and inactivate beta-lactamases
• Historical background


  • Sir Alexander Fleming accidentally discovered the antibacterial properties of penicillin from Penicillium notatum in 1929
  • Florey & Chain purify penicillin and introduced it into therapy
  • Pasteur & Joubert discovered the anthrax bacilli
• Clavulanic acid


  • An antibiotic isolated from Streptomyces clavuligeris
  • Has a very weak antibacterial activity
• Antibiotic


  A substance produced by microorganisms, which has the capacity of inhibiting the growth and even of destroying other microorganisms (Waksman, 1942)