Skip to main content
SpringerLink
Log in

Beta-Lactam Antibiotics

  • Chapter
  • First Online:
Book cover Antibiotic Discovery and Development

Abstract

The beta-lactam antibiotics constitute one of the oldest and most popular classes of anti-bacterial agents. The beta-lactams first used for human therapy, were isolated from molds, particularly Penicillium chrysogenum. The story of the discovery of the antibacterial properties of molds goes back to the earliest recorded history [50, 135]: in 3000 BC, Chinese scribes documented the use of moldy soya beans to treat infected wounds [22]; in the sixteenth century BC, a Greek peasant woman reputedly cured wounded soldiers using mold scraped from cheese [82]; the Ebers papyrus from Egypt, dated around 1550 BC, gives a prescription for treating infected wounds with “spoiled barley bread” [52]; in the second century BC, soldiers in Sri Lanka applied poultices made from moldy oilcakes to wounds. The therapeutic usage of molds continued in such ways through to the nineteenth century without much consideration of how the molds might be exerting their influence.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 189.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Abraham EP (1956) New penicillins and other antibiotics containing nitrogen and sulphur. Giorn. Microbiol. 2:102–115

    Google Scholar 

  2. Abraham EP (1991) From penicillins to cephalosporins. In: Kleinkauf H, von Döhren H (eds) 50 years of penicillin application. History and trends. Technische Universität Berlin, PUBLIC Ltd, Czech Republic, pp 7–23

    Google Scholar 

  3. Abraham EP, Chain E (1940) An enzyme from bacteria able to destroy penicillin. Nature 146:837

    Article  CAS  Google Scholar 

  4. Abraham EP, Newton GGF (1961) The structure of cephalosporin C. Biochem J 79: 377–393

    PubMed  CAS  Google Scholar 

  5. Abraham EP, Chain E, Fletcher CM et al (1941) Further observations on penicillin. Lancet ii:177–188

    Article  CAS  Google Scholar 

  6. Abraham EP, Chain E, Florey H et al (1949) Antibiotics, vol 2. Oxford University Press, London, pp 631–671

    Google Scholar 

  7. Adlington RM, Baldwin JE, Chen B et al (1997) Design and synthesis of novel monocyclic β-lactam inhibitors of prostate specific antigen. Bioorg Med Chem Lett 7:1689–1694

    Article  CAS  Google Scholar 

  8. Albers-Schoenberg G, Arison BH, Hensens OD, et al. (1978) Structure and absolute configuration of thienamycin. J. Am. Chem. Soc., 100:6491–6499

    Article  Google Scholar 

  9. Allsop AE, Brooks G, Bruton G et al (1995) Penem inhibitors of bacterial signal peptidase. Bioorg Med Chem Lett 5:443–448

    Article  CAS  Google Scholar 

  10. Andrus A, Baker F, Bouffard FA et al (1985) Structure activity relationships among some totally synthetic carbapenems. In: Brown AG, Roberts SM (eds) Recent advances in the chemistry of β-lactam antibiotics, Special Publication No. 52. Royal Society of Chemistry, London, pp 86–99

    Google Scholar 

  11. Angehrn P, Böhringer M, Hubschwerlen C et al (1996) Bridged carbacephems as antibacterial agents: structure-activity relationships. In: Poster F158 abstracts of the 36th interscience conference on antimicrobial agents and chemotherapy, New Orleans, 15–18 Sept 1996

    Google Scholar 

  12. Aoki H, Sakai H, Kohsaka M et al (1976) Nocardicin A, a new monocyclic beta-lactam antibiotic. I. Discovery, isolation and characterization. J Antibiot (Tokyo) 29:492–500

    CAS  Google Scholar 

  13. Aoyama Y, Uenaka M, Konoike T et al (2000) 1-Oxacephem-based human chymase inhibitors: discovery of stable inhibitors in human plasma. Bioorg Med Chem Lett 10:2403–2406

    Article  PubMed  CAS  Google Scholar 

  14. Asai M, Haibara K, Muroi M et al (1981) Sulfazecin, a novel beta-lactam antibiotic of bacterial origin. Isolation and chemical characterization. J Antibiot (Tokyo) 34:621–627

    CAS  Google Scholar 

  15. Baldwin JE, Chan MF, Gallacher G et al (1984) γ-Lactam analogues of penicillanic and carbapenicillanic acids. Tetrahedron 40:4513–4525

    Article  CAS  Google Scholar 

  16. Baldwin JE, Lowe C, Schofield CJ et al (1986) Lactam analogue of penems possessing antibacterial activity. Tetrahedron Lett 27:3461–3464

    Article  CAS  Google Scholar 

  17. Barbachyn MR, Tuominen TC (1990) Synthesis and structure-activity relationships of monocarbams leading to U-78608. J Antibiot 43:1199–1203

    PubMed  CAS  Google Scholar 

  18. Basker MJ, Edmondson RA, Knott SJ et al (1984) In vitro antibacterial properties of BRL 36650, a novel 6 alpha-substituted penicillin. Antimicrob. Ag. Chemother. 26:734–740.

    PubMed  CAS  Google Scholar 

  19. Basker MJ, Branch CL, Finch SC et al (1986) Studies on semisynthetic 7α-formamidocephalosporins. I. Structure-activity relationships in some 7α-formamimidocephalosporins. J Antibiot 39:1788–1791

    PubMed  CAS  Google Scholar 

  20. Bentley PH, Clayton JP (1977) Nuclear transformations using benzyl (6-isocyano-penicillinates). In: Elks J (ed) Recent advances in the chemistry of β-lactam antibiotics, Special Publication No. 28. The Chemical Society, London, pp 68–72

    Google Scholar 

  21. Behrens OK, Corse J, Jones RG et al (1948) Biosynthesis of penicillins. II. Utilization of deuterophenylacetyl-N15-DL-valine in penicillin biosynthesis. J Biol Chem 175:765–769

    Google Scholar 

  22. Bickel L (1972) “Rise Up to Life” Melbourne: Sun Books

    Google Scholar 

  23. Bonnefoy A, Dupuis-Hamelin C, Steier V et al (2004) In vitro activity of AVE1330A, an innovative broad-spectrum non-beta-lactam beta-lactamase inhibitor. J Antimicrob Chemother 54:410–417

    Article  PubMed  CAS  Google Scholar 

  24. Boschetti CE, Mascaretti OA, Cricco JA et al (1995) Synthesis and elastase inhibitory ­activity of 6α.chloro-2, 2-dimethyl-3α-(pivaloyloxy)methylpenam sulfone, 6α-chloro-2, 2-dimethyl-3-exo-methylenepenam sulfone, benzyl and methyl 6α-substituted penicillate sulfones. Bioorg Med Chem 4:95–100

    Article  Google Scholar 

  25. Boucher HW, Talbot GH, Bradley JS et al (2005) Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin Infect Dis 48:1–12

    Article  Google Scholar 

  26. Boyd DB, Foster BJ, Hatfield LD et al (1986a) γ-Lactam analogues of carbapenems. Tetrahedron Letts 2:3457–3460

    Google Scholar 

  27. Boyd DB, Elzey TK, Hatfield LD et al (1986b) γ-Lactam analogues of the penems. Tetrahedron Letts 27:3453–3456

    Google Scholar 

  28. Branch CL, Basker MJ, Finch SC et al (1987) Studies on semisynthetic 7α-formamidocephalosporins. III. Synthesis and antibacterial activity of some 7β-[D-2-(aryl)-2-[(4-ethyl-2,3-­dioxopiperazin-1yl)-carbonylamino]acetamido]-7α-formamido-ceph-3-em-4-carboxylate derivatives. J Antibiot 40:646–651

    PubMed  CAS  Google Scholar 

  29. Brandl E, Spitzy KH (1991) 35 years of oral treatment with acid-stable penicillin (Penicillin V). In: Kleinkauf H, von Döhren H (eds) 50 years of penicillin application. History and trends. Technische Universität Berlin, PUBLIC Ltd, Czech Republic, pp 60–63

    Google Scholar 

  30. Brenwald NP, Andrews J, Fraise AP (2006) Activity of mecillinam against AmpC β-lactamase-producing Escherichia coli. J Antimicrob Chemother 58:223–224

    Article  PubMed  CAS  Google Scholar 

  31. Brotzu G (1948) Richerche su di un nuovo antibiotico. Lavori dell’istituto d’Igiene di Cagliari, pp 1–11

    Google Scholar 

  32. Brown AG (1987) Discovery and development of new β-lactam antibiotics. Pure Appl Chem 59:475–484

    Article  CAS  Google Scholar 

  33. Brown AG, Butterworth D, Cole M et al (1976) Naturally-occurring beta-lactamase inhibitors with antibacterial activity. J Antibiot (Tokyo) 29:668–669

    CAS  Google Scholar 

  34. Brown RB, Klar J, Lemeshow S et al (1986) Enhanced bleeding with cefoxitin or moxalactam. Statistical analysis within a defined population of 1493 patients. Arch Intern Med 146: 2159–2164

    Article  PubMed  CAS  Google Scholar 

  35. Burke JR, Gregor KR, Padmanabha R et al (1998) A beta-lactam inhibitor of cytosolic phospholipase A2 which acts in a competitive, reversible manner at the lipid/water interface. J Enzyme Inhib 13:195–206

    Article  PubMed  CAS  Google Scholar 

  36. Bush K, Macalintal C, Rasmussen BA et al (1993) Kinetic interactions of tazobactam with beta-lactamases from all major structural classes. Antimicrob Agents Chemother 37:851–858

    PubMed  CAS  Google Scholar 

  37. Buynak JD (2006) Understanding the longevity of the β-lactam antibiotics and of antibiotic/β-lactamase inhibitor combinations. Biochem Pharmacol 71:930–940

    Article  PubMed  CAS  Google Scholar 

  38. Cama LD, Christensen BG (1974) Total synthesis of β-lactam antibiotics. VII. Total synthesis of (±)-1-oxacephalothin. J Am Chem Soc 96:7582–7584

    Article  PubMed  CAS  Google Scholar 

  39. Cama LD, Leanza WJ, Beattie TR et al (1972) Substituted penicillin and cephalosporin derivatives. I. Stereospecific introduction of the C-6(7) methoxy group. J Am Chem Soc 94: 1408–1410

    Article  PubMed  CAS  Google Scholar 

  40. Clarke HT, Johnson JR & Robinson R (1949) “The Chemistry of Penicillin”. Princeton: Princeton University Press

    Google Scholar 

  41. Chain EB, Florey HW, Gardner AD et al (1940) Penicillin as a therapeutic agent. Lancet ii:226–228

    Article  CAS  Google Scholar 

  42. Cherry PC, Newell CE, Watson NS (1978) Preparation of the 7-oxo-4-oxa-1-azabicyclo[3.2.0]hept-2-ene system and the reversible cleavage of its oxazoline ring. J Chem Soc Chem Commun 11:469–470

    Article  Google Scholar 

  43. Christenson JG, Pruess DL, Talbot MK et al (1988) Antibacterial properties of (2,3)-α- and (2,3)-β-methylene analogs of penicillinG. Antimicrob Agents Chemother 32:1005–1011

    PubMed  CAS  Google Scholar 

  44. de Araujo OR, Cardoso D, da Silva B et al (2007) Cefepime restriction improves gram-negative overall resistance patterns in neonatal intensive care unit. Braz J Infect Dis 11:277–280

    Article  PubMed  Google Scholar 

  45. Doherty JB, Ashe BM, Barker PL, et al (1990) Inhibition of human leukocyte elastase. 1. Inhibition by C-7-substituted cephalosporin tert-butyl esters. http://www.ncbi.nlm.nih.gov/pubmed/2391691\o. J Med Chem. 33:2513–21

  46. Doyle TW, Belleau B, Luh BY et al (1977) Nuclear analogs of β-lactam antibiotics. I. Synthesis of O-2-isocephems. Can J Chem 55:468–483

    Article  CAS  Google Scholar 

  47. Doyle TW, Belleau B, Luh BY et al (1977) Nuclear analogs of β-lactam antibiotics. II. Synthesis of O-2-isocephems. Can J Chem 55:468–483

    Article  CAS  Google Scholar 

  48. Drusano G, Castanheira M, Liu W et al (2009) Pharmacodynamically-linked variable for the combination of ceftaroline plus Novexel104. In: Abstracts of 19th European congress of clinical microbiology and infectious diseases (ECCMID), Helsinki, 16–19 May 2009

    Google Scholar 

  49. Du B, Chen D, Liu D et al (2003) Restriction of third-generation cephalosporin use decreases infection-related mortality. Crit Care Med 31:1088–1093

    Article  PubMed  CAS  Google Scholar 

  50. Du Vineaud V, Carpenter FH (1949). The γ-lactam of benzylhomopenicilloic acid and related compounds. pp. 1004–17. In: Clarke HT, Johnson JR, Robinson R (eds) The Chemistry of Penicillin. Princeton: Princeton University Press

    Google Scholar 

  51. Duschene E (1897) Contribution à l’etude de la concurrence vitale chez les microorganisms. Thesis, Lyon

    Google Scholar 

  52. Ebbell B (1937) The Papyrus Ebers: the greatest Egyptian medical document. Levin and Munskgaard, Copenhagen

    Google Scholar 

  53. English AR, Retsems JA, Girard AE et al (1978) CP-45,899, a beta-lactamase inhibitor that extends the antibacterial spectrum of beta-lactams: initial bacteriological characterization. Antimicrob Agents Chemother 14:414–419

    PubMed  CAS  Google Scholar 

  54. Firestone RA, Barker PL, Pisano JM et al (1990) Monocyclic β-lactam inhibitors of human leukocyte elastase. Tetrahedron 46:2255–2262

    Article  CAS  Google Scholar 

  55. Fleming A (1929) On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenzae. Br J Exp Pathol 10:226–236

    CAS  Google Scholar 

  56. Florey HW (1945) Use of microorganisms for therapeutic purposes. Br Med J ii:635–642

    Article  Google Scholar 

  57. Fraser-Moodie W (1971) Struggle against infection. Proc R Soc Med 64:87–94

    PubMed  CAS  Google Scholar 

  58. Fuchs PC, Jones RN, Barry LW et al (1986) In vitro activity of carumonam (RO 17–2301), BMY-28142, aztreonam and ceftazidime against 7,620 consecutive clinical bacterial isolates. Diagn Microbiol Infect Dis 5:345–349

    Article  PubMed  CAS  Google Scholar 

  59. Glinka T, Blais J, Dudley M et al (2005) Poster F-1455. A novel series of 3-heteroarylthio carbacephems with activity against resistant Gram-positive bacteria. In: Abstracts of the 45th interscience conference on antimcrobial agents and chemotherapy, Washington, DC, 16–19 Dec 2005

    Google Scholar 

  60. Gonzalez Leiza M, Perez-Diaz JC, Ayala J et al (1994) Gene sequence and biochemical characterization of FOX-1 from Klebsiella pneumoniae, a new AmpC-type plasmid-mediated beta-lactamase with two molecular variants. Antimicrob Agents Chemother 38:2150–2157

    PubMed  CAS  Google Scholar 

  61. Gratia A, Dath S (1925) Propriétés bacteriolytiques de certaines moisissures. C R Soc Biol 91:1442–1443

    Google Scholar 

  62. Guthikonda RN, Cama LD, Christensen BG (1974) Total synthesis of beta-lactam antibiotics. VIII. Stereospecific total synthesis of (plus or minus)-1-carbacephalothin. J Am Chem Soc 96:7584–7585

    Article  PubMed  CAS  Google Scholar 

  63. Hagmann WK, Kissinger AL, Shah SK, et al (1993) Orally active beta-lactam inhibitors of human leukocyte elastase. 2. Effect of C-4 substitution. J Med Chem. 36:771–7

    Google Scholar 

  64. Han WT, Trehan AK, Wright JJK et al (1995) Azetidin-2-one derivatives as inhibitors of thrombin. Bioorganic Med Chem 3:1123–1143

    Article  CAS  Google Scholar 

  65. Harada S, Tsubotani S, Hida T et al (1986) Structure of lactivicin, an antibiotic having a new nucleus and similar biological activities to β-lactam antibiotics. Tetrahedron Lett 27: 6229–6232

    Article  CAS  Google Scholar 

  66. Hashiguchi S, Natsugari H, Ochiai M (1988) Synthesis of γ-lactam analogues of carbapenems with substituted-thio groups at the C-3 position. J Chem Soc Perkin Trans 1:2345–2352

    Article  Google Scholar 

  67. Hatano K, Takeda S, Nakai T et al (2005) In vitro anti-Pseudomonas aeruginosa activity of novel parenteral cephalosporin FR264205. In: Poster F-1452, 45th interscience conference on antimicrobial agents and chemotherapy, Washington, DC, 16–19 Dec 2005

    Google Scholar 

  68. Hebeisen P, Heinze-Krauss I, Angehrn P et al (2001) In vitro and in vivo properties of RO 63–9141, a novel broad-spectrum cephalosporin with activity against methicillin-resistant staphylococci. Antimicrob Agents Chemother 45:825–836

    Article  PubMed  CAS  Google Scholar 

  69. Heinze-Krauss I, Angehrn P, Charnas RL et al (1998) Structure-based design of beta-lactamase inhibitors. 1. Synthesis and evaluation of bridged monobactams. J Med Chem 41:3961–3971

    Article  PubMed  CAS  Google Scholar 

  70. Herzberg O, Moult J (1987) Bacterial resistance to beta-lactam antibiotics: crystal structure of beta-lactamase from Staphylococcus aureus PC1 at 2.5 A resolution. Science 23:694–701

    Google Scholar 

  71. Hill DA, Herford T, Parratt D (1998) Antibiotic usage and methicillin-resistant Staphylococcus aureus: an analysis of causality. J Antimicrob Chemother 42:676–677

    Article  PubMed  CAS  Google Scholar 

  72. Hopkins MH, Silverman RB (1992) β-Lactams: a new class of conformationally-rigid inhibitors of γ-aminobutyric acid aminotransferase. J Enzyme Inhib Med Chem 6:125–129

    Article  CAS  Google Scholar 

  73. Hubschwerlen C, Angehrn P, Böhringer M et al (1996) Bridged isooxa- and iso-cephems as β-lactamase inhibitors and antibacterials: synthesis and structure-activity relationships. In: Poster F157 abstracts of the 36th interscience conference on antimicrobial agents and chemotherapy, New Orleans

    Google Scholar 

  74. Hwu JR, Tsay SC, Hakimelahi S (1998) Syntheses of new isodethiaazacephems as potent antibacterial agents. J Med Chem 41:4681–4685

    Article  PubMed  CAS  Google Scholar 

  75. Imada A, Kitano K, Kintaka K et al (1981) Sulfazecin and isosulfazecin, novel b-lactam antibiotics of bacterial origin. Nature 289:590–591

    Article  PubMed  CAS  Google Scholar 

  76. Imada A, Kondo M, Okonogi K et al (1985) In vitro and in vivo antibacterial activities of carumonam (AMA.1080), a new N-sulfonated monocyclic β-lactam antibiotic. Antimicrob Agents Chemother 27:821–827

    PubMed  CAS  Google Scholar 

  77. Ishikawa T, Kamiyama K, Nakayama Y et al (2001) Studies on anti-MRSA parenteral cephalosporins. III. Synthesis and antibacterial activity of 7-beta-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)-alkoxyiminoacetamido]-3-[(E)-2-(1-alkylimidazo[1,2-β]pyridazinium-6-yl)thiovinyl]-3-cephem-4-carboxylates and related compounds. J Antibiot 54:257–277

    PubMed  CAS  Google Scholar 

  78. Jacobson KL, Cohen SH, Inciardi F et al (1995) The relationship between antecedent ­antibiotic use and resistance to extended-spectrum cephalosporins in group I beta-lactamase-producing organisms. Clin Infect Dis 21:1107–1113

    Article  PubMed  CAS  Google Scholar 

  79. Jamieson CE, Lambert PA et al (2003) In vitro and in vivo activities of AM-112, a novel oxapenem. Antimicrob Agents Chemother 47:1652–1657

    Article  PubMed  CAS  Google Scholar 

  80. Karady S, Pines SH, Weinstock LM et al (1972) Semisynthetic cephalosporins via a novel acyl exchange reaction. J Am Chem Soc 94:1410–1411

    Article  PubMed  CAS  Google Scholar 

  81. Katayama N, Nozaki Y, Okonogi K et al (1985) Formadicins, new monocyclic beta-lactam antibiotics of bacterial origin. I. Taxonomy, fermentation and biological activities. J Antibiot (Tokyo) 38:1117–1127

    CAS  Google Scholar 

  82. Kavaler L (1967) “Mushrooms, Moulds and Miracles: the Strange Realm of Fungi”. London: George Harrap

    Google Scholar 

  83. Knight WB, Green BG, Chabin RM (1992) Specificity, stability, and potency of monocyclic.beta.-lactam inhibitors of human leukocyte elastase. Biochemistry 31:8160–8170

    Article  PubMed  CAS  Google Scholar 

  84. Kuo D, Weidner J, Griffin P et al (1994) Determination of the kinetic parameters of Escherichia coli leader peptidase activity using a continuous assay: the pH dependence and time-dependent inhibition by beta-lactams are consistent with a novel serine protease mechanism. Biochemistry 33:8347–8354

    Article  PubMed  CAS  Google Scholar 

  85. Lattrell R, Duerckheimer W, Limbert M (1988) Synthesis and structure-activity relationships in the cefpirome series. III 7α-methoxy and 7α-formamido analogues of cefpirome. J Antibiot 41:1409–1417

    PubMed  CAS  Google Scholar 

  86. Lazell HG (1975) From pills to penicillin: the Beecham story. Heinemann, London

    Google Scholar 

  87. Lim D, Strynadka NCJ (2002) Structural basis for the β-lactam resistance of PBP2a from methicillin-resistant Staphylococcus aureus. Nat Struct Biol 9:870–876

    PubMed  CAS  Google Scholar 

  88. Lister J (1875) A contribution to the germ theory of putrefaction and other fermentative changes, and to the natural history of torulae and bacteria. Trans R Soc Edinb 27:313

    Google Scholar 

  89. Livermore DM, Tulkens PM (2009) Temocillin revived. J Antimicrob Chemother 63:243–245

    Google Scholar 

  90. Lovering A, Danel F, Page MGP et al (2006) Mechanism of action of ceftobiprole: structural basis for anti-MRSA activity. In: Poster P-1586, 16th European congress of clinical microbiology and infectious diseases (ECCMID), Nice, Apr 2006

    Google Scholar 

  91. Lund F, Tybring L (1972) 6β-amidinopenicillanic acid – a new group of antibiotics. Nat New Biol 236:135–137

    PubMed  CAS  Google Scholar 

  92. Marchand-Brynaert J, Ghosez L (1990) Non b-lactam analogs of penicillin and cephalosporins. In: Lukas G, Ohno M (eds) Recent progress in the chemical synthesis of antiobiotics. Springer, Berlin/Heidelberg, pp 727–792

    Chapter  Google Scholar 

  93. Mastalerz H, Menard M, Vinet V et al (1988) An examination of O-2-isocephems as orally absorbable antibiotics. J Med Chem 31:1190–1196

    Article  PubMed  CAS  Google Scholar 

  94. Miossec C, Poirel L, Livermore D et al (2007) In vitro activity of the new β-lactamase inhibitor NXL104: restoration of ceftazidime efficacy against carbapenem-resistant Enterobacteriaceae strains. In: Poster F1-318, 47th ICAAC, Chicago, 17–20 Sept 2007

    Google Scholar 

  95. Möllmann U, Heinisch L, Bauernfeind A, Köhler T, Ankel-Fuchs D. (2009) Siderophores as drug delivery agents: application of the “Trojan Horse” strategy. BioMetals 22:615–624

    Google Scholar 

  96. Moyer AJ, Coghill RD (1947) Penicillin X. The effect of phenylacetic acid on penicillin production. J Bacteriol 53:329–341

    CAS  Google Scholar 

  97. Nagarajan R, Boeck LD, Gorman M et al (1987) Beta-lactam antibiotics from Streptomyces. Applied Microbiol. Biotech 27:240–246

    Google Scholar 

  98. Narisada M, Yoshida T, Onoue H et al (1979) Synthetic studies on β-lactam antibiotics. 10. Synthesis of 7β-[2-carboxy-2-(4-hydroxyphenyl)-acetamido-7α-methoxy-3-[[(1-methyl-1 H-tetrazol-5-yl)-thio]-1-oxa-1-dethia-3-cephem-4-carboxylic acid disodium salt(6059-S) and its related 1-oxacephems. J Med Chem 22:757–759

    Article  PubMed  CAS  Google Scholar 

  99. Natsugari H, Kawano Y, Morimoto A et al (1987) Synthesis of lactivicin and its derivatives. J. Chem. Soc., Chem. Commun 1987 (2):62–63

    Google Scholar 

  100. Nayler JHC (1991) Semi-synthetic approaches to novel penicillins. TIBS 16:234–237

    Google Scholar 

  101. Newton GGF, Abraham EP (1954) Degradation, structure and some derivatives of cephalosporin N. Biochem J 58:103–111

    PubMed  CAS  Google Scholar 

  102. Newton GGF, Abraham EP (1956) Isolation of cephalosporin C, a penicillin-like antibiotic containing D-α-aminoadipic acid. Biochem J 62:651–658

    PubMed  CAS  Google Scholar 

  103. Ogasa T, Saito H, Hashimoto Y et al (1989) 3H-1-carbacephem compounds. Chem Pharm Bull 37:315–321

    Article  PubMed  CAS  Google Scholar 

  104. Ono H, Nozaki Y, Katayama N et al (1984) Cephabacins, new cephem antibioticcs of bacterial origin. Discovery and taxonomy of the producing organisms and fermentation. J Antibiot 37:1528–1535

    PubMed  CAS  Google Scholar 

  105. Osborne NF, Broom NJP, Coulton S et al (1989) A novel and stereocontrolled synthesis of (5R)-(Z)-6-(1-methyl-1,2,3-triazol-4-ylmethylene)penem-3-carboxylic acid, a potent broad spectrum b-lactamase inhibitor. J Chem Soc Chem Commun 1989:371–373

    Article  Google Scholar 

  106. Page MGP (1993) The kinetics of non-stoichiometric bursts of β-lactam hydrolysis catalysed by class C β-lactamases. Biochem J 295:295–304

    PubMed  CAS  Google Scholar 

  107. Page MGP (2000) β-lactamase inhibitors. Drug Resist Updat 3:109–125

    Article  PubMed  CAS  Google Scholar 

  108. Page MGP (2007) Emerging cephalosporins. Expert Opin Emerg Drugs 12:511–524

    Article  PubMed  CAS  Google Scholar 

  109. Page MGP (2007) Ceftobiprole – a case study. Expert Opin Drug Discov 2:115–129

    Article  CAS  Google Scholar 

  110. Page MGP (2007) Resistance mediated by penicillin-binding proteins. In: Bonomoand RA, Tolmasky M (eds) Enzyme-mediated resistance to antibiotics. Mechanisms, dissemination and prospects for inhibition. ASM Press, Washington, DC, pp 81–100

    Google Scholar 

  111. Page MGP (2008) Extended-spectrum β-lactamases. Structure and kinetic mechanism. Clin Microbiol Infect 14(suppl 1):63–74

    Article  PubMed  CAS  Google Scholar 

  112. Page MGP, Desarbre E, Geier C et al (2007) Activity of BAL30376 against gram-negative bacteria. In: Poster F1-312, 47th ICAAC, Chicago, 17–20 Sept 2007

    Google Scholar 

  113. Pasteur L, Joubert J (1877) Charbon et septicemia. C R Acad Sci 85:101–105

    Google Scholar 

  114. Petri WA (2001) Antimicrobial agents penicillins, cephalosporins, and other lactam antibiotics. In: Hardman JG, Limbird LE, Gilman AG (eds), Goodman and Gillman’s The pharmacological basis of therapeutics, 10th edn. New York: McGraw_Hill Professional. pp. 1189–1218

    Google Scholar 

  115. Petersen PJ, Jones CH, Venkatesan AM et al (2009) Efficacy of piperacillin combined with the penem β-lactamase inhibitor BLI-489 in murine models of systemic infection. Antimicrob Agents Chemother 53:1698–1700

    Article  PubMed  CAS  Google Scholar 

  116. Patterson JE (2001) Antibiotic utilization. Is there an effect on antimicrobial resistance? Chest 119(Suppl 2):S426–S430

    Article  Google Scholar 

  117. Pfaendler HR, Weisner F, Metzger K (1993) Synthesis and antibacterial activity of (1’R, 5R, 6R)-2-tert-butyl-6-(1’-hydroxyethyl)oxapenem-3-carboxylic acid. Bioorg. Med. Chem. Lett. 3:2211–2218

    Google Scholar 

  118. Pieroth I (1991) Penicillin – a survey from discovery to industrial production. In: Kleinkauf H, von Döhren H (eds) 50 years of penicillin application History and trends. Technische Universität Berlin, PUBLIC Ltd, Czech Republic, pp 7–23

    Google Scholar 

  119. Reading C, Cole M (1977) Clavulanic acid: a beta-lactamase-inhibiting beta-lactam from Streptomyces clavuligerus. Antimicrob Agents Chemother 11:852–857

    PubMed  CAS  Google Scholar 

  120. Rice L (2001) Evolution and clinical importance of extended-spectrum β-lactamases. Chest 119(Suppl 2):S391–S396

    Article  Google Scholar 

  121. Rothstein JD, Patel S, Regan MR et al (2005) β-lactam antibiotics offer neuroprotection by increasing glutamate transporter expression. Nature 433:73–77

    Article  PubMed  CAS  Google Scholar 

  122. Sandanayaka VP, Prashad AS (2002) Resistance to β-lactam antibiotics: structure and mechanism based design of β-lactamase inhibitors. Curr Med Chem 9:1145–1165

    PubMed  CAS  Google Scholar 

  123. Sanderson JSB (1871) Appendix 5 – Further report of researches concerning the intimate pathology of contagion. The origin and distribution of microzymes (bacteria) in water, and the circumstances which determine their existence in the tissue and liquids. Twelfth Report of the Medical Officer of the Privy Council (1869), Parliamentary Papers, pp 229–256

    Google Scholar 

  124. Schentag JJ, Hyatt JM, Carr JR et al (1998) Genesis of methicillin-resistant Staphylococcus aureus (MRSA), how treatment of MRSA infections has selected for vancomycin-resistant Enterococcus faecium, and the importance of antibiotic management and infection control. Clin Infect Dis 26:1204–1214

    Article  PubMed  CAS  Google Scholar 

  125. Selwyn S (1979) Pioneer work on the ‘penicillin phenomenon’. J Antimicrob Chemother 5:249–255

    Article  PubMed  CAS  Google Scholar 

  126. Shama G (2003) Pilzkrieg: the German wartime quest for penicillin. Microbiol Today 30:120–123

    Google Scholar 

  127. Shetty N, Shulman RI, Scott GM (1999) An audit of first generation cephalsoporin usage. J Hosp Infect 41:229–232

    Article  PubMed  CAS  Google Scholar 

  128. Shoji J, Kato T, Sakazaki R et al (1984) Chitinovorins A, B, and C, novel β-lactam antibiotics of bacterial origin. J Antibiot 37:1486–1490

    PubMed  CAS  Google Scholar 

  129. Singh PD, Young MG, Johnson JH et al (1984) Bacterial production of 7-formamidocephaölosporins. Isolation and structure determination. J Antibiot 37:773–780

    PubMed  CAS  Google Scholar 

  130. Slocombe B, Basker MJ, Bentley PH (1981) BRL 17421, a novel β-lactam antibiotic, highly resistant to β-lactamases, giving high and prolonged serum levels in humans. Antimicrob Agents Chemother 20:38–46

    PubMed  CAS  Google Scholar 

  131. Stapley EO, Jackson M, Hernandez S et al (1972) Cephamycins, a new family of /3-lactamantibiotics. I. Production by Actinomycetes, including Streptomyces lactamnidurams, sp n.. Antimicrob. Ag Chemother 2:122–131

    Google Scholar 

  132. St-Denis Y, Augelli-Szafran CE, Bachand B et al (1998) Potent bicyclic lactam inhibitors of thrombin: Part I: P3 modifications. Bioorg Med Chem Lett 8:3193–3198

    Article  PubMed  CAS  Google Scholar 

  133. Sutton JC, Bolton SA, Hartl KS et al (2002) Synthesis and SAR of 4-carboxy-2-azetidinone mechanism-based tryptase inhibitors. Bioorg Med Chem Lett 12:3229–3233

    Article  PubMed  CAS  Google Scholar 

  134. Sykes RB, Cimarusti CM, Bonner DP et al (1981) Monocyclic β-lactam antibiotics produced by bacteria. Nature 291:489–492

    Article  PubMed  CAS  Google Scholar 

  135. Sykes RB, Bonner DP, Bush K et al (1982) Azthreonam (SQ 26,776) a synthetic monobactam specifically active against aerobic gram-negative bacteria. Antimicrob Agents Chemother 21:85–92

    PubMed  CAS  Google Scholar 

  136. Tager M (1976) John F. Fulton, coccidioidomycosis, and penicillin. Yale J Biol Med 49:391–398

    PubMed  CAS  Google Scholar 

  137. Takeda S, Nakai T, Wakai Y et al (2007) In vitro and in vivo activities of a new cephalosporin, FR264205, against Pseudomonas aeruginosa. Antimicrob Agents Chemother 51:826–830

    Article  PubMed  CAS  Google Scholar 

  138. Tamura N, Matsushita Y, Yoshioka K, Ochiai M (1988) Synthesis of lactivicin analogues. Tetrahedron 44:3231–3240

    Google Scholar 

  139. Tamura N, Matsushita Y, Kawano Y, Yoshioka K (1990) Synthesis and Antibacterial Activity of Lactivicin Derivatives. Chem Pharm Bull 38:116–122

    Google Scholar 

  140. Tanaka SK, Summerill RAS, Minassian BF et al (1987) In vitro evaluation of tigemonam, a novel oral monobactam. Antimicrob Agents Chemother 31:219–225

    PubMed  CAS  Google Scholar 

  141. Tayler JHC (1991) Discovery of the semisynthetic penicillins. In: Kleinkauf H, von Döhren H (eds) 50 years of penicillin application. History and trends. Technische Universität Berlin, PUBLIC Ltd, Czech Republic, pp 64–74

    Google Scholar 

  142. Ternansky RJ, Draheim SE (1990) [3.3.0] pyrazolidinones: an efficient synthesis of a new class of synthetic antibacterial agents. Tetrahedron Lett 31:2805–2808

    Article  CAS  Google Scholar 

  143. Ternansky RJ, Draheim SE, Pike AJ et al (1993) Discovery and structure-activity relationship of a series of 1-carba-1-dethiacephems exhibiting activity against methicillin-resistant Staphylococcus aureus. J Med Chem 36:1971–1976

    Article  PubMed  CAS  Google Scholar 

  144. Tiberio V (1895) Sugli estratti di alcune muffe. Ann. d’Igiene Sperimentale. 1. Istituto di Igene della R. Università di Napoli

    Google Scholar 

  145. Tosoni AL, Glass DG, Goldsmith L (1958) Crystalline p-aminobenzylpenicillin: preparation and some properties. Biochem J 69:476–480

    PubMed  CAS  Google Scholar 

  146. Tsuji T, Satoh H, Narisada M, Hamashima Y, Yoshida T. (1985) Synthesis and antibacterial activity of 6315-S, a new member of the oxacephem antibiotic. J Antibiot. (Tokyo). 38:466–76

    PubMed  CAS  Google Scholar 

  147. Tsuji K, Tsubouchi H, Yasumura K et al (1996) Synthesis and structure-activity relationships of cephalosporins, 2-isocephems, and 2-oxaisocephems with C-3’ or C-7 catechol or related aromatics. Bioorg Med Chem 4:2135–2149

    Article  PubMed  CAS  Google Scholar 

  148. Tyndall J (1876) The optical deportment of the atmosphere in relation to the phenomena of putrefaction and infection. Philos Trans R Soc Lond 166:27–63

    Article  Google Scholar 

  149. Ueda Y, Kanazawa K, Eguchi K et al (2005) In vitro and in vivo antibacterial activities of SM-216601, a new broad-spectrum parenteral carbapenem. Antimicrob Agents Chemother 49:4185–4196

    Article  PubMed  CAS  Google Scholar 

  150. Urbach A, Muccioli GG, Stern E et al (2008) 3-Alkenyl-2-azetidinones as fatty acid amide hydrolase inhibitors. Bioorg Med Chem Lett 18:4163–4167

    Article  PubMed  CAS  Google Scholar 

  151. Venkatesan AM, Agarwal A, Abe T et al (2004) Novel imidazole substituted 6-methylidene-penems as broad-spectrum β-lactamase inhibitors. Bioorg Med Chem 12:5807–5817

    Article  PubMed  CAS  Google Scholar 

  152. Wainwright M (1989) Moulds in folk medicine. Folklore 100:162–166

    Google Scholar 

  153. Wainwright M, Swan HT (1986) C.G. Paine and the earliest surviving clinical records of penicillin therapy. Med Hist 30:42–56

    PubMed  CAS  Google Scholar 

  154. Watanabe Y, Minami S, Hayashi T et al (1995) In vitro antibacterial properties of T-5575 and T-5578 novel parenteral 2-carboxypenams. Antimicrob Agents Chemother 39:2787–2791

    PubMed  CAS  Google Scholar 

  155. Waxman DJ, Strominger JL (1983) Penicillin-binding proteins and the mechanism of action of beta-lactam antibiotics. Annu Rev Biochem 52:825–869

    Article  PubMed  CAS  Google Scholar 

  156. Wells JS, Trejo WH et al (1982) SQ 26,180, a novel monobactam. I. Taxonomy, fermentation and biological properties. J Antibiot 35:184–188

    PubMed  CAS  Google Scholar 

  157. Wells JS, Trejo WH, Principe PA et al (1982) EM5400, a family of monobbactam antibiotics produced by Agrobacterium radiobacter. I Taxonomy, fermentation and biological properties. J Antibiot 35:184–188

    PubMed  CAS  Google Scholar 

  158. Winkler JD, Sung CM, Chabot-Flecher M et al (1998) β-lactams SB 212047 and SB 216754 are irreversible, time-dependent inhibitors of coenzyme A-independent transacylase. Mol Pharmacol 53:322–329

    PubMed  CAS  Google Scholar 

  159. Woodward RB (1977) Recent advances in the chemistry of β-lactam antibiotics. In: Elks J (ed) Recent advances in the chemistry of β-lactam antibiotics, Special publication No.23. Royal Society of Chemistry, London

    Google Scholar 

  160. Yoakim C, Ogilvie WW, Cameron DR et al (1998) Potent beta-lactam inhibitors of human cytomegalovirus protease. Antivir Chem Chemother 9:379–387

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Basilea Pharmaceutica International Ltd, Basel, Switzerland

    Malcolm G. P. Page

Authors
  1. Malcolm G. P. Page
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Malcolm G. P. Page .

Editor information

Editors and Affiliations

  1. , Senior Principal Scientist, AstraZeneca Pharmaceuticals LP, Gatehouse Dr. 35, Waltham, 02451, Massachusetts, USA

    Thomas J. Dougherty

  2. Achillion Pharmaceuticals, Inc., George St. 300, New Haven, 06511, Connecticut, USA

    Michael J. Pucci

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Page, M.G.P. (2012). Beta-Lactam Antibiotics. In: Dougherty, T., Pucci, M. (eds) Antibiotic Discovery and Development. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-1400-1_3

Download citation

Publish with us

Policies and ethics

Search

Navigation