Use of Penicillinase-Resistant Penicillins to Increase the Susceptibility of Gram-Negative Bacteria to Antibiotics
Authors: W. EDMUND FARRAR
Journal: Annals of Internal Medicine (1967)

Article1 October 1967Use of Penicillinase-Resistant Penicillins to Increase the Susceptibility of Gram-Negative Bacteria to AntibioticsW. EDMUND FARRAR JR., M.D., F.A.C.P., NOEL M. O'DELL, B.S., JANE M. KRAUSE, A.B.W. EDMUND FARRAR JR., M.D., F.A.C.P.Search for more papers by this author, NOEL M. O'DELL, B.S.Search for more papers by this author, JANE M. KRAUSE, A.B.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-67-4-733 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptMany 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...References1. HAMILTON-MILLER JM: Penicillinase from Klebsiella aerogenes. A comparison with penicillinases from gram-positive species. Biochem. J. 87: 209, 1963. CrossrefMedlineGoogle Scholar2. SMITHHAMILTON-MILLER JTJM: Differences between penicillinases from gram-positive and gram-negative bacteria. Nature (London) 197: 976, 1963. CrossrefMedlineGoogle Scholar3. POLLOCK MR: Enzymes destroying penicillin and cephalosporin. Antimicrob. Agents Chemother. 4: 292, 1964. Google Scholar4. AYLIFFE GA: Cephalosporinase and penicillinase activity of Gram-negative bacteria. J. Gen. Microbiol. 40: 119, 1965. CrossrefMedlineGoogle Scholar5. PERCIVALBRUMFITTLOUVOIS AWJD: The role of penicillinase in determining natural and acquired resistance of gram-negative bacteria to penicillins. J. Gen. Microbiol. 32: 77: 1963. CrossrefMedlineGoogle Scholar6. SUTHERLAND R: The nature of the insensitivity of Gram-negative bacteria towards penicillins. J. Gen. Microbiol. 34: 85, 1964. CrossrefMedlineGoogle Scholar7. HOLTSTEWART RJGT: Production of amidase and beta-lactamase by bacteria. J. Gen. Microbiol. 36: 203, 1964. CrossrefMedlineGoogle Scholar8. HAMILTON-MILLER JM: Modes of resistance to benzylpenicillin and ampicillin in twelve Klebsiella strains. J. Gen. Microbiol. 41: 175, 1965. CrossrefMedlineGoogle Scholar9. ABRAHAMNEWTON EPGG: A comparison of the action of penicillinase on benzyl-penicillin and cephalosporin N and the competitive inhibition of penicillinase by cephalosporin C. Biochem. J. 63: 628, 1956. CrossrefMedlineGoogle Scholar10. SABATHABRAHAM LDEP: Synergistic action of penicillins and cephalosporins against Pseudomonas pyocyanea. Nature (London) 204: 1066, 1964. CrossrefMedlineGoogle Scholar11. HAMILTON-MILLERSMITH JMJT: Inhibition of penicillinases from gram-positive and gram-negative bacteria by substrate analogues. Nature (London) 201: 999, 1964. CrossrefMedlineGoogle Scholar12. SABATHJAGOABRAHAM LDMEP: Cephalosporinase and penicillinase activities of a B-lactamase from Pseudomonas pyocyanea. Biochem. J. 96: 739, 1965. CrossrefMedlineGoogle Scholar13. O'CALLAGHANMUGGLETONKIRBYRYAN CHPWSMDM: Inhibition of gram-negative B-lactamase decomposition of cephaloridine and cephalothin by other cephalosporins (abstract), in Proceedings of the Sixth Interscience Conference on Antimicrobial Agents and Chemotherapy, Philadelphia, Pa., October 26-28, 1966. American Society for Microbiology, Ann Arbor, 1966, p. 74. Google Scholar14. SUTHERLANDBATCHELOR RFR: Synergistic activity of penicillins against penicillinase-producing Gram-negative bacteria. Nature (London) 201: 868, 1964. CrossrefMedlineGoogle Scholar15. HAMILTON-MILLERSMITHKNOX JMJTR: Potentiation of penicillin action by inhibition of penicillinase. Ibid., p. 867. Google Scholar16. ACREDSUTHERLAND PR: Antibacterial activities of combinations of ampicillin and cloxacillin (abstract), in Proceedings of the Sixth Interscience Conference on Antimicrobial Agents and Chemotherapy, Philadelphia, Pa., October 26-28, 1966. American Society for Microbiology, Ann Arbor, 1966, p. 73. Google Scholar17. BACHBUONOCHISHOLMPRICEPURSIANOGOUREVITCH JANDKETAA: In vitro and in vivo synergism of ampicillin and B-lactamase-resistant penicillins. Ibid., p. 74. Google Scholar18. OSWALDREEDYWRIGHT EJRJWW: Antibiotic combinations: an in vitro study of antistaphylococcal effects of erythromycin plus penicillin, streptomycin, or tetracycline, in Antimicrobial Agents and Chemotherapy. Braun-Brumfield, Ann Arbor, 1961, p. 904. Google Scholar19. BRACKENPATTERSON ECJL: Applications of the two-dimensional tube dilution technique, in Proceedings of the Fourth Interscience Conference on Antimicrobial Agents and Chemotherapy, New York, N. Y., October 26-28, 1964. American Society for Microbiology, Ann Arbor, 1964, p. 83. Google Scholar20. ANDERSONLEWIS ESMJ: Drug resistance and its transfer in Salmonella typhimurium. Nature (London) 206: 579, 1965. CrossrefMedlineGoogle Scholar21. EDWARDSEWING PRWH: Identification of Enterobacteriaceae. Burgess Publishing Co., Minneapolis, 1962, p. 207. Google Scholar22. SABATHPOSTICFINLAND LDBM: Laboratory studies on methicillin. With special reference to patients treated for staphylococcal infections. Amer. J. Med. Sci. 244: 484, 1962. CrossrefMedlineGoogle Scholar23. KLEINFINLAND JOM: Nafcillin. Antibacterial action and absorption and excretion in normal young men. Amer. J. Med. Sci. 246: 10, 1963. CrossrefMedlineGoogle Scholar24. KLEINSABATHFINLAND JOLDM: Laboratory studies on oxacillin. I. In vitro activity against staphylococci and some other bacterial pathogens. II. Absorption and urinary excretion in normal young men. Amer. J. Med. Sci. 245: 399, 1963. CrossrefMedlineGoogle Scholar25. KLEINFINLAND JOM: Ampicillin: activity in vitro and absorption and excretion in normal young men. Ibid., p. 544. Google Scholar26. KLEINEICKHOFFTILLESFINLAND JOTCJGM: Cephalothin: activity in vitro, absorption and excretion in normal subjects and clinical observations in 40 patients. Amer. J. Med. Sci. 248: 640, 1964. CrossrefMedlineGoogle Scholar27. SHIRLEYMOORE RLJW: Pseudomonas aeruginosa urinary-tract infection (letter to the editor). New Eng. J. Med. 273: 283, 1965. CrossrefGoogle Scholar28. SABATHELDERMCCALLSTEIGBIGELFINLAND LDHACENHM: Synergistic penicillin combinations in the treatment of human urinary-tract infections, in Proceedings of the Sixth Interscience Conference on Antimicrobial Agents and Chemotherapy, Philadelphia, Pa., October 26-28, 1966. American Society for Microbiology, Ann Arbor, 1966, p. 75. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: W. EDMUND FARRARJR., M.D., F.A.C.P.; NOEL M. O'DELL, B.S.; JANE M. KRAUSE, A.B.Affiliations: Atlanta, GeorgiaFrom the Department of Preventive Medicine and Community Health, Emory University School of Medicine, Atlanta, Ga.This investigation was supported in part by grants from Bristol Laboratories, Inc., Syracuse, N. Y., and Eli Lilly & Co., Indianapolis, Ind.A preliminary report of this study was presented at the Sixth Interscience Conference on Antimicrobial Agents and Chemotherapy, October 26-28, 1966, Philadelphia, Pa.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. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byKinetic Profiling of Homogeneous and Heterogeneous Biocatalysts in Continuous Flow by Online Mass SpectrometrySymposium on Tissue Penetration of Antibiotics: Stockholm, September 15–16, 1977R Factor-Mediated and Chromosomal Resistance to Ampicillin in Escherichia coliMechanism of Synergistic Effects of β-Lactam Antibiotic Combinations on Gram-Negative BacilliCOMBINATIONS OF ANTIBIOTICSUse of michaelis-menten kinetics in the analysis of synergism between β-lactam antibioticsRelationship Between β-Lactamase Activity and Resistance of Enterobacter to CephalothinA NOTE ON INTERACTIONS BETWEEN METHICILLIN AND OTHER PENICILLINS IN DISC SENSITIVITY TESTS OF STAPHYLOCOCCUS EPIDERMIDISStructure–Activity Relationships Among Semisynthetic CephalosporinsERYTHROPOIETIC PROTOPORPHYRIA IN TWO SISTERS 1 October 1967Volume 67, Issue 4Page: 733-743KeywordsAntibioticsBacteriaChemotherapyDrugsEnzymesGram negative bacteriaPenicillinPrevention, policy, and public healthPreventive medicinePseudomonas ePublished: 1 December 2008 Issue Published: 1 October 1967 PDF downloadLoading ...