β-Lactam antibiotics with novel nuclei

  • F. O’Grady


Since the isolation of the penicillin nucleus a huge number of semisynthetic penams and cephems have been generated by manipulation of the side chain at the 6 position of 6 amino penicillanic acid and at the 7 and 3 positions of 7 amino-cephalosporanic acid. The objectives of this manipulation have been to secure improvements over the parent compounds in four properties: (1) degree of intrinsic antibacterial activity; (2) extension of antibacterial range to include organisms resistant to the parent compound — an objective that has centred to a substantial extent on Pseudomonas aeruginosa, but has extended to include other naturally resistant Gram-negative rods such as Enterobacter, Serratia, indole-positive Proteus and anaerobic bacteria; (3) stability to a wide range of β-lactamases, the major cause of resistance in an increasing variety of organisms to earlier β-lactams; and (4) improvement in pharmacokinetic behaviour.


Antibacterial Activity Clavulanic Acid Neisseria Gonorrhoeae Lactam Antibiotic Penicillanic Acid 
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  1. AOKI, H., SAKI, H., KOSHAKA, M., KONOMI, T., HOSADA, J., KUBOCHI, Y., GUCHI, E. & IMANAKA, H. (1976). Nocardicin A, a new monocyclic β-lactam antibiotic. I. Discovery, isolation and characterisation. J. Antibiot., 29, 492–500.PubMedCrossRefGoogle Scholar
  2. BANKS, R.M. & O’GRADY, F. (1983). Therapeutic significance of Nocardicin A stimulation of phagocyte function in experimental Pseudomonas aeruginosa infection. Br. J. exp. Path., 64, 231–237.Google Scholar
  3. BIRNBAUM, J., STAPLEY, E.O., MILLER, A.K., WALLICK, H., HENDLIN, D. & WOODRUFF, H.B. (1978). Cefoxitin, a semi-synthetic cephamycin: a microbiological overview. J. antimicrob. Chemother. 4, Suppl. B, 15–32.PubMedCrossRefGoogle Scholar
  4. BROWN, A.G. (1981). New naturally occurring β-lactam antibiotics and related compounds. J. antimicrob. Chemother., 7, 15–48.PubMedCrossRefGoogle Scholar
  5. CARMINE, A.A., BROGDEN, R.N., HEEL, R.C., ROMANKIEWICZ, J.A., SPEIGHT, T.M. & AVERY, G.S. (1983). Moxalactam (Latamoxef): a review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs, 26, 279–333.PubMedCrossRefGoogle Scholar
  6. GANGULY, A.K., GIRIJAVALLABHAN, V.M., McCOMBIE, S., PINTO, P., RIZUI, R., JEFFREY, P.D. & LIN, S. (1982). Synthesis of Sch. 29482 — a novel penem antibiotic. J. antimicrob. Chemother. 9, Suppl. C, 1–5.PubMedCrossRefGoogle Scholar
  7. GREENWOOD, D. & O’GRADY, F. (1973). FL1060: a new β-lactam antibiotic with novel properties. J. din. Path., 26, 1.CrossRefGoogle Scholar
  8. KAHAN, F.M., KROOP, H., SUNDERLOF, J.G. & BIRNBAUM, J. (1983). Thienamycin: development of imipenem-cilastatin. J. antimicrob. Chemother., 12, Suppl. D., 1–35.PubMedCrossRefGoogle Scholar
  9. LUND, F. & TYBRING, L. (1972). 6.β-amidinopenicillanic acids — a new group of antibiotics. Nature, 236, 135–137.Google Scholar
  10. MORITA, K., NOMURA, H., NUMATA, M., OCHIAI, M. & YONEDA, M. (1980). An approach to broad spectrum cephalosporin compounds. Phil. Trans. R. Soc. Lond., B 289, 181–190.CrossRefGoogle Scholar
  11. NISHIDA, M., MINE, Y., NONOYAMA, S. & KOJO, H. (1977). Nocardicin A, a new monocyclic β-lactam antibiotic III: In vitro evaluation. J. Antibiot., 30, 917–925.PubMedCrossRefGoogle Scholar
  12. READING, C. (1982). The biochemistry and mode of action of augmentin. In Augmentin: Clavulanate-potentiated amoxycillin. Leigh, D.A. & Robinson, P.P.W. (eds) pp. 5–21, Excerpta Medica.Google Scholar
  13. SANDERS, C.C. & SANDERS, W.E. Jr (1983). Emergence of resistance during therapy with the newer β-lactam antibiotics: role of inducible β-lactamases and implications for the future. Rev. infect. Dis., 5, 639–648.PubMedCrossRefGoogle Scholar
  14. SLOCOMBE, B., BASKER, M.J., BENTLEY, P.H., CLAYTON, J.P., COLE, M., COMBER, K.R., DIXON, R.A., EDMONSON, R.A., JACKSON, D., MERRIKIN, D.J. & SUTHERLAND, R. (1981). BRL-17421, a novel β-lactam antibiotic, highly resistant to β-lactamases, giving high and prolonged serum levels in humans. Antimicrob. Ag. Chemother., 20, 38–46.CrossRefGoogle Scholar
  15. SYKES, R.B., BONNER, D.P., BUSH, K., GEORGOPAPADAKOU, N.H. & WELLS, J.S. (1981). Monobactams — monocyclic β-lactam antibiotics produced by bacteria. J. antimicrob. Chemother., 8, Suppl. E., 1–16.PubMedCrossRefGoogle Scholar

Copyright information

© Macmillan Publishers Limited 1984

Authors and Affiliations

  • F. O’Grady
    • 1
  1. 1.Department of Microbiology and PHLS LaboratoryQueen’s Medical CentreNottinghamUK

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