In many areas of infectious diseases, there is a disparity between the intensity of medical need and the perceived commercial potential for the appropriate products. Wellknown examples include malaria and tuberculosis. For a variety of reasons, the same disparity is becoming reality for new antibacterial compounds which could address existing and emerging pathogens that are resistant to current antibiotics. In this chapter, we will review the history of antibiotic discovery and development to put everything else in an appropriate context. We will then explore the scientifi c challenges that have resulted in the paucity of novel antibacterials in today’s pipeline. Then we will examine the various factors that have coalesced to make antibacterials seem less commercially attractive for large companies. We will compare the situation in biotechnology and small pharmaceutical companies with that in large pharmaceutical companies. Finally, we will speculate on the future of antibacterial discovery and development given the emerging trends in science, in the marketplace, within the regulatory environment, and in the context of the pharmaceutical business.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Lax E. The Mold in Dr. Florey's Coat. Henry Holt and Co, New York, 2004
Abraham EP, Chain E. An enzyme from bacteria able to destroy penicillin. Nature 146:837, 1940
Wallmark G, Finland M. Phage types and antibiotic susceptibility of pathogenic staphylococci. Results at Boston City Hospital 1959–1960 and a comparison with strains of previous years. JAMA 175:886–897, 1961
Zierdt CH, Robertson A, Williams RL, MacLowry JD. Computer analysis of Staphylococcus aureus phage typing data from 1957 to 1975, citing epidemiological trends and natural evolution within the phage typing system. Applied and Environmental Microbiology 39:623–629, 1980
Nahmias A, Sakurai N, Blumberg R, Doe Ge A, Sulzer C. The Staphylococcus 80/81 complex: epidemiological and laboratory observations. Journal of Infectious Diseases. 109:211–222, 1961
Nahmias AJ, Eickhoff TC. Staphylococcal infections in hospitals. Recent developments in epidemiologic and laboratory investigation. New England Journal of Medicine. 265:120–128 contd, 1961
Nahmias AJ, Eickhoff TC. Staphylococcal infection in hospitals. Recent developments in epidemiologic and laboratory investigation. New England Journal of Medicine. 265:74–81 contd, 1961
Nahmias AJ, Eickhoff TC. Staphylococcal infections in hospitals. Recent developments in epidemiologic and laboratory investigation. New England Journal of Medicine. 265:177–182 concl, 1961
Public Health Laboratory Service Report. 1966. Necropsy survey of Staphylococcal infections in lying in hospitals, pp. 313–319
Swartz M. 1997. Use of antimicrobial agents and drug resistance. New England Journal of Medicine. 337:491–492
Acred P, Brown DM, Turner DH, Wright D. Pharmacology of methicillin. British Journal of Pharmacology and Chemotherapy. 17:70–81, 1961
Rosenblatt JE, Barrett JE, Brodie JL, Kirby WM. Comparison of in vitro activity and clinical pharmacology of doxycycline with other tetracyclines. Antimicrobial Agents and Chemotherapy. 6:134–141, 1966
Kuck NA, Redin GS, Forbes M. Activity of minocycline and other tetracyclines against tetracycline-sensitive and -resistant staphylo-cocci. Proceedings of the Society for Experimental Biology and Medicine. 136(2):479–481, 1971
McCormick MH, McGuire JM, Pittenger GE, Pittenger RC, Stark WM. Vancomycin, a new antibiotic. I. Chemical and biologic properties. Antibiotics Annual. 3:606–611, 1955–1956
Maggi N, Pasqualucci CR, Ballotta R, Sensi P. Rifampicin: a new orally active rifamycin. Chemotherapy. 11(5):285–292, 1966
Hirai K, Ito A, Abe Y, Suzue S, Irikura T, Inoue M, Mitsuhashi S. Comparative activities of AM-715 {norfloxacin} and pipemidic and nalidixic acids against experimentally induced systemic and urinary tract infections. Antimicrobial Agents and Chemotherapy. 19(1):188–189, 1981
Miller TW, Goegelman RT, Weston RG, Putter I, Wolf FJ. Cephamycins, a new family of beta-lactam antibiotics. II. Isolation and chemical characterization. Antimicrobial Agents and Chemotherapy. 2(3):132–135, 1972
Leigh DA. Antibacterial activity and pharmacokinetics of clin-damycin. Journal of Antimicrobial Chemotherapy. 7(Suppl A):3–9, 1981
Reading C, Cole M. Clavulanic acid: a beta-lactamase-inhibiting beta-lactam from Streptomyces clavuligerus. Antimicrobial Agents and Chemotherapy. 11(5):852–857, 1977
Waitz JA, Moss EL Jr, Drube CG, Weinstein MJ. Comparative activity of sisomicin, gentamicin, kanamycin, and tobramycin. Antimicrobial Agents and Chemotherapy. 2(6):431–437, 1972
Retsema J, Girard A, Schelkly W, Manousos M, Anderson M, Bright G, Borovoy R, Brennan L, Mason R. Spectrum and mode of action of azithromycin (CP-62,993), a new 15-membered-ring macrolide with improved potency against gram-negative organisms. Antimicrobial Agents and Chemotherapy. 31(12):1939–1947, 1987
Kuck NA, Redin GS. In vitro and in vivo activity of piperacil-lin, a new broad-spectrum semisynthetic penicillin. Journal of Antibiotics. 31(11):1175–1182, 1978
Abraham EP, Newton GG. The cephalosporins. Advances in Chemotherapy. 2:23–90, 1965
Wise R, Andrews JM, Edwards LJ. In vitro activity of Bay 09867 [ciprofloxacin], a new quinoline derivative, compared with those of other antimicrobial agents. Antimicrobial Agents and Chemotherapy. 23(4):559–564, 1983
Wise R, Andrews JM, Bedford KA. In vitro study of clavulanic acid in combination with penicillin, amoxycillin, and carbenicillin. Antimicrobial Agents and Chemotherapy. 13(3):389–393, 1978
Reiner R, Weiss U, Brombacher U, Lanz P, Montavon M, Furlenmeier A, Angehrn P, Probst PJ. Ro 13-9904/001 [ceftri-axone], a novel potent and long-acting parenteral cephalosporin. Journal of Antibiotics. 33(7):783–786, 1980
Payne DJ, Miller WH, Berry V, Brosky J, Burgess WJ, Chen E, DeWolf Jr WE Jr, Fosberry AP, Greenwood R, Head MS, Heerding DA, Janson CA, Jaworski DD, Keller PM, Manley PJ, Moore TD, Newlander KA, Pearson S, Polizzi BJ, Qiu X, Rittenhouse SF, Slater-Radosti C, Salyers KL, Seefeld MA, Smyth MG, Takata DT, Uzinskas IN, Vaidya K, Wallis NG, Winram SB, Yuan CC, Huffman WF. Discovery of a novel and potent class of FabI-directed antibacterial agents. Antimicrobial Agents and Chemotherapy. 46(10):3118–3124, 2002
Marrakchi H, Dewolf WE Jr, Quinn C, West J, Polizzi BJ, So CY, Holmes DJ, Reed SL, Heath RJ, Payne DJ, Rock CO, Wallis NG. Characterization of Streptococcus pneumoniae enoyl-(acyl-carrier protein) reductase (FabK). Biochemical Journal. 370(Pt 3): 1055–1062, 2003
Chen D, Hackbarth C, Ni ZJ, Wu C, Wang W, Jain R, He Y, Bracken K, Weidmann B, Patel DV, Trias J, White RJ, Yuan Z. Peptide deformylase inhibitors as antibacterial agents: identification of VRC3375, a proline-3-alkylsuccinyl hydroxamate derivative, by using an integrated combinatorial and medicinal chemistry approach. Antimicrobial Agents and Chemotherapy. 48(1): 250–261, 2004
Wang J, Soisson SM, Young K, Shoop W, Kodali S, Galgoci A, Painter R, Parthasarathy G, Tang YS, Cummings R, Ha S, Dorso K, Motyl M, Jayasuriya H, Ondeyka J, Herath K, Zhang C, Hernandez L, Allocco J, Basilio A, Tormo JR, Genilloud O, Vicente F, Pelaez F, Colwell L, Lee SH, Michael B, Felcetto T, Gill C, Silver LL, Hermes JD, Bartizal K, Barrett J, Schmatz D, Becker JW, Cully D, Singh SB. Platensimycin is a selective FabF inhibitor with potent antibiotic properties. Nature. 44:358–361, 2006
Brickner SJ, Hutchinson DK, Barbachyn MR, Manninen PR, Ulanowicz DA, Garmon SA, Grega KC, Hendges SK, Toops DS, Ford CW, Zurenko GE. Synthesis and antibacterial activity of U-100592 and U-100766, two oxazolidinone antibacterial agents for the potential treatment of multidrug-resistant gram- positive bacterial infections. Journal of Medicinal Chemistry. 39(3): 673–679, 1996
Paterson DL. The epidemiological profile of infections with multidrug-resistant Pseudomonas aeruginosa and Acinetobacter species. Clinical Infectious Disease. 43:S43–S48, 2006
Shlaes DM, Projan SJ, Edwards JE Jr. Antibiotic Discovery: State of the State. Am Soc for Microbiol News. 70:275–281, 2004
Gregory JM, Anusha K, Rachel JG, Gregory EF, Linda KM, Roberta BC, David AT, for the EMERGEncy ID Net Study Group* Methicillin-resistant S. aureus infections among patients in the emergency department. New England Journal of Medicine. 355:666–674, 2006
Robinson DA, Kearns AM, Holmes A, Morrison D, Grundmann H, Edwards G, O'Brien FG, Tenover FC, McDougal LK, Monk AB, Enright MC. Re-emergence of early pandemic Staphylococcus aureus as a community-acquired methicillin-resistant clone. Lancet 365:1256–1258, 2005
Bad bugs, no drugs: as antibiotic R&D stagnates, a public health crisis brews. Infectious Diseases Society of America, Alexandria, VA, 2004
Talbot GH, Bradley J, Edwards JE Jr., Gilbert D, Scheld M, Bartlett JG. Bad bugs need drugs: an update on the development pipeline from the, antimicrobial availability task force of the infectious diseases society of America. Clinical Infectious Disease 42:657–668, 2006
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Humana Press, a part of Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Shlaes, D.M., Projan, S.J. (2009). Antimicrobial Resistance Versus the Discovery and Development of New Antimicrobials. In: Mayers, D.L. (eds) Antimicrobial Drug Resistance. Infectious Disease. Humana Press. https://doi.org/10.1007/978-1-59745-180-2_4
Download citation
DOI: https://doi.org/10.1007/978-1-59745-180-2_4
Publisher Name: Humana Press
Print ISBN: 978-1-60327-592-7
Online ISBN: 978-1-59745-180-2
eBook Packages: MedicineMedicine (R0)