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Use of Penicillinase-Resistant Penicillins to Increase the Susceptibility of Gram-Negative Bacteria to Antibiotics
- W. EDMUND FARRAR, JR., M.D., F.A.C.P.;
- NOEL M. O'DELL, B.S.; and
- JANE M. KRAUSE, A.B.
- Requests for reprints should be addressed to W. Edmund Farrar, Jr., M.D., Emory University School of Medicine, 69 Butler St., SE, Atlanta, Ga. 30303.
Excerpt
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
Acknowledgment
Most of the drugs used in these studies were generously supplied by Bristol Laboratories, Inc., Eli Lilly & Co., and Wyeth Laboratories.
We are indebted to Drs. J. A. Shulman and J. R. Boring of the National Communicable Disease Center for furnishing us with strains of Pseudomonas for testing.
Article and Author Information
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From the Department of Preventive Medicine and Community Health, Emory University School of Medicine, Atlanta, Ga.
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This investigation was supported in part by grants from Bristol Laboratories, Inc., Syracuse, N. Y., and Eli Lilly & Co., Indianapolis, Ind.
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- Received April 10, 1967.
- Accepted May 31, 1967.
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