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Beta-Lactam Antibiotics & Other Inhibitors of Cell Wall Synthesis

Beta-lactam compounds

  1. Penicillins (e.g. penicillin G)-These have the greatest activity against gram-positive organisms, gram-negative cocci, and non-beta-lactamase-producing anaerobes and little activity against gram-negative rods. They are susceptible to hydrolysis by beta-lactamases.
  • Antistaphylococcal penicillins (e.g.nafcillin)-These penicillins are resistant to staphylococcal beta-lactamases. They are active against staphylococci and streptococci but inactive against enterococci, anaerobic bacteria, and gram-negative cocci and rods.
  • Extended-spectrum penicillins (ampicillin and the antipseudomonal penicillins)-These drugs retain the antibacterial spectrum of penicillin and have improved activity against gram-negative organisms, but they are destroyed by beta-lactamases
    • Clinical Uses
  • Except for amoxicillin, oral penicillins should not be given at mealtimes (instead, give 1-2 hours before or after) to minimize binding to food proteins and acid inactivation.
  • Penicillin: Penicillin G is the drug of choice for infections caused by streptococci, meningococci, enterococci, penicillin-susceptible pneumococci, non-beta-lactamase-producing staphylococci,Treponema pallidum, and many other spirochetes, Bacillus anthracis, clostridium species, actinomyces, and other gram-positive rods and non-beta-lactamase-producing gram-negative anaerobic organisms.
  • Penicillin V, the oral form of penicillin, is indicated only in minor infections because of its relatively poor bioavailability, the need for dosing four times a day, and its narrow antibacterial spectrum. Amoxicillin is often used instead
  • A single injection of benzathine penicillin,1.2 million units intramuscularly, is satisfactory for the treatment of beta-hemolytic streptococcal pharyngitis. A similar injection given intramuscularly once every 3-4 weeks provides satisfactory prophylaxis against reinfection with beta-hemolytic streptococci. Penicillin G benzathine, 2.4 million units intramuscularly once a week for 1-3 weeks, is effective in the treatment of syphilis
  • Penicillins Resistant to Staphylococcal Beta-Lactamase (Methicillin, Nafcillin, and Isoxazolyl Penicillins): The sole indication for the use of these agents is infection by beta-lactamase-producing staphylococci, though penicillin-susceptible strains of streptococci and pneumococci are also susceptible to these semisynthetic penicillins.
  • Extended-Spectrum Penicillins (Aminopenicillins, Carboxypenicillins, and Ureidopenicillins): These drugs, which in general retain the spectrum of activity of penicillin G, differ in having greater activity against gram-negative bacteria due to their enhanced ability to penetrate the gram-negative outer membrane. Like penicillin G, they are inactivated by beta-lactamases.
  • Aminopenicillins, ampicillin, and amoxicillin, have the same spectrum and activity, but amoxicillin is better absorbed from the gut. A dosage of 250-500 mg of amoxicillin three times daily is equivalent to the same amount of ampicillin given four times daily. These drugs are given orally to treat urinary tract infections, sinusitis, otitis, and lower respiratory tract infections. Ampicillin and amoxicillin are the most active oral beta-lactam antibiotics against penicillin-resistant pneumococci and are the preferred beta-lactam antibiotics for treating infections suspected to be caused by these resistant strains. Ampicillin, at dosages of 4-12 g/d intravenously, is useful for treating serious infections caused by penicillin-susceptible organisms, including anaerobes, enterococci, Listeria monocytogenes, and susceptible strains of gram-negative cocci and bacilli such as E Coli, H influenzae, and salmonella species.

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