β-LACTAMASES HAVE BEEN THE SCOURGE OF ANTIBIOTIC TREATMENT TOO LONG!
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viewpoints HAVE BEEN THE SCOURGE OF ANTIBIOTIC TREATMENT TOO LONG! But, now, clavulanic acid will inhibit them and allow penicillins to act The arrival of benzylpenicillin (penicillin G) to medicine heralded a new era in the use of antibiotics. However, the Achilles heel of benzylpenicillin turned out to be its susceptibility to bacterial These enzymes open benzylpenicillin's ring and destroy its antibacterial activity. Staphylococci in the 1950s and 60s became penicillin-resistant solely because of the production of Pharmacologists then sought either to find antibiotics resembling benzylpenicillin or substances which would bind strongly to the blocking its penicillin-destroying effects. In 1960, the penicillinase-resistant antibiotic, methicillin, was synthesised. Later, orally active cloxacillin and flucloxacillin were discovered. Like benzylpenicillin, these compounds had little activity against Gram-negative rods. Ampicillin, amoxycillin and the cephalosporins extended the antibacterial spectrum of penicillin. Nevertheless, the remained a problem, and those produced by Gram-negative rods were found to differ from those produced by staphylococci in their ability to degrade penicillins and cephalosporins. 21 years after the discovery of methicillin, the first inhibitor, clavulanic acid, became available. Clavulanic acid has little antibacterial activity of its own. However, it is a potent and progressive inhibitor of of both chromosomal and plasmid origin from Staphylococcus aureus, Escherichia coli, Klebsiella spp, Porteus mirabilis, Haemophi/us influenzae, Neisseria gonorrhoeae, and Bacteroides spp. Clavulanic acid lowers the MIC of many penicillins and cephalosporins for strains. It has recently been combined with amoxycillin in a commercial, orally active product. The pair correspond well in their pharmacokinetic behaviour. Patients treated with amoxycillin-clavulanic acid have not experienced disturbances in gut flora. 'Whether the repair to amoxycillin's beta-lactamase lability is sufficiently secure to control the emergence and overgrowth of resistant strains if the agent comes to be widely used, only time will tell. O'Grady, F.W.: British Medical Journal 284: 369 (6 Feb 1982) 2 INPHARMA 20 Feb 1982 0156-2703/82/0220-0002/0$01.00/0 © ADIS Press
Transcript of β-LACTAMASES HAVE BEEN THE SCOURGE OF ANTIBIOTIC TREATMENT TOO LONG!
viewpoints ~-LACTAMASES HAVE BEEN THE SCOURGE OF ANTIBIOTIC TREATMENT TOO LONG!
But, now, clavulanic acid will inhibit them and allow penicillins to act The arrival of benzylpenicillin (penicillin G) to medicine heralded a new era in the use of antibiotics. However, the Achilles heel of
benzylpenicillin turned out to be its susceptibility to bacterial ~-lactamases. These enzymes open benzylpenicillin's ~-lactam ring and destroy its antibacterial activity. Staphylococci in the 1950s and 60s became penicillin-resistant solely because of the
production of ~-lactamases. Pharmacologists then sought either to find ~-lactamase-resistant antibiotics resembling
benzylpenicillin or substances which would bind strongly to the ~-lactamase, blocking its penicillin-destroying effects. In 1960, the penicillinase-resistant antibiotic, methicillin, was synthesised. Later, orally active cloxacillin and flucloxacillin were discovered. Like benzylpenicillin, these compounds had little activity against Gram-negative rods. Ampicillin, amoxycillin and the
cephalosporins extended the antibacterial spectrum of penicillin. Nevertheless, the ~-lactamases remained a problem, and those produced by Gram-negative rods were found to differ from those produced by staphylococci in their ability to degrade penicillins
and cephalosporins. 21 years after the discovery of methicillin, the first ~-lactamase inhibitor, clavulanic acid, became available. Clavulanic acid has little antibacterial activity of its own. However, it is a potent and progressive inhibitor of ~-lactamases of both
chromosomal and plasmid origin from Staphylococcus aureus, Escherichia coli, Klebsiella spp, Porteus mirabilis, Haemophi/us
influenzae, Neisseria gonorrhoeae, and Bacteroides spp. Clavulanic acid lowers the MIC of many penicillins and cephalosporins for ~-lactamase-producing strains. It has recently been
combined with amoxycillin in a commercial, orally active product. The pair correspond well in their pharmacokinetic behaviour.
Patients treated with amoxycillin-clavulanic acid have not experienced disturbances in gut flora. 'Whether the repair to amoxycillin's beta-lactamase lability is sufficiently secure to control the emergence and
overgrowth of resistant strains if the agent comes to be widely used, only time will tell. O'Grady, F.W.: British Medical Journal 284: 369 (6 Feb 1982)
2 INPHARMA 20 Feb 1982 0156-2703/82/0220-0002/0$01.00/0 © ADIS Press
