W. EDMUND FARRAR, M.D., F.A.C.P.; NOEL M. O'DELL, B.S.; JANE M. KRAUSE, A.B.
FARRAR WE, O'DELL NM, KRAUSE JM. Use of Penicillinase-Resistant Penicillins to Increase the Susceptibility of Gram-Negative Bacteria to Antibiotics. Ann Intern Med. 1967;67:733-743. doi: 10.7326/0003-4819-67-4-733
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Published: Ann Intern Med. 1967;67(4):733-743.
Many gram-negative bacteria elaborate beta-lactamases capable of inactivating penicillin and related antibiotics (1-4). The presence of such enzymes appears to be an important factor in the resistance of these bacteria to the penicillins and cephalosporins (5-8). On the other hand, certain semisynthetic penicillins, such as methicillin, are only slowly hydrolyzed by the penicillinases of gram-negative bacteria but may exhibit high affinities for these enzymes. The semisynthetic penicillins thus may form relatively stable enzyme-substrate complexes and are capable of competitively inhibiting the activity of betalactamases (9-13) even though they are relatively ineffective as antibacterial agents against gram-negative bacilli. This type of
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