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Drug Development for Drug-Resistant Pathogens

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Antimicrobial Drug Resistance

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Abstract

Antibiotic therapy is arguably the most significant achievement of mankind in the twentieth century. Together with vaccines, it has had a tremendous impact in prolonging life. After many successful years following World War II, antibacterial drugs gradually lost their efficacy because of bacterial resistance. Nowadays, certain multidrug-resistant hospital strains cause infections that are almost impossible to treat, and lead to mortality rates not dissimilar to those of the pre-antibiotic era. The “antibiotic crisis” has become a matter of priority for governments, regulators, as well as the medical and scientific communities. This chapter provides a brief history of small-molecule antibiotics from the discovery of penicillin to the present day. The second section assesses medical need and key factors contributing to the business landscape. Finally, the last section reviews the current antibacterial clinical pipeline and most recent drug launches.

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References

  1. Kardos N, Demain AL. Penicillin: the medicine with the greatest impact on therapeutic outcomes. Appl Microbiol Biotechnol. 2011;92:677–87.

    Article  CAS  PubMed  Google Scholar 

  2. Fleming A. On the antibacterial action of cultures of a Penicillium, with special reference to their use in the isolation of B. influenza. Br J Exp Path. 1929;10:226–36.

    CAS  Google Scholar 

  3. Lax E. The mold in Dr. Florey’s coat. Henry Holt and Co; 2004.

    Google Scholar 

  4. American Chemical Society. 2014. The discovery and development of penicillin 1928–1945 Commemorative Booklet. http://www.acs.org/content/acs/en/education/whatischemistry/landmarks/flemingpenicillin.html. Accessed 6 Dec 2014.

  5. Nobel Media AB. 2014. Nobel Prize in physiology or medicine 1945 http://www.nobelprize.org/nobel_prizes/medicine/laureates/1945/ Accessed 6 Dec 2014.

  6. Otten H. Domagk and the development of the sulphonamides. J Antimicrob Chemother. 1986;17:689–96.

    Article  CAS  PubMed  Google Scholar 

  7. Woods D. The relation of p-aminobenzoic acid to the mechanism of action of sulphanilamide. Brit J Exp Pathol. 1940;21:74–90.

    CAS  Google Scholar 

  8. Rolinson GN, Geddes AM. The 50th anniversary of the discovery of 6-aminopenicillanic acid (6-APA). Int J Antimicrob Agents. 2007;29:3–8.

    Article  CAS  PubMed  Google Scholar 

  9. Abraham EP, Chain E. An enzyme from bacteria able to destroy penicillin. Nature. 1940;146:837.

    Article  CAS  Google Scholar 

  10. Spink WW, Ferris V. Penicillin-resistant staphylococci: mechanisms involved in the development of resistance. J Clin Invest. 1947;26:379–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Finland M, Haight TH. Antibiotic resistance of pathogenic staphylococci: study of five hundred strains isolated at Boston City Hospital from October, 1951, to February, 1952. AMA Arch Intern Med. 1953;91:143–58.

    Article  CAS  PubMed  Google Scholar 

  12. Jacoby G, Bush K. Beta-lactam resistance in the 21st century. In: White DG, Alekshun MN, McDermott PF, editors. Frontiers in antimicrobial resistance. Washington, DC: ASM Press; 2005. p. 53–65.

    Chapter  Google Scholar 

  13. Fair RJ, Tor Y. Antibiotics and Bacterial Resistance in the 21st Century. Perspect Med Chem. 2014;6:25–64.

    Google Scholar 

  14. Centers for Disease Control and Prevention. 2013. Antibiotic resistance threats in the United States; 2013. http://www.cdc.gov/media/releases/2013/p0916-untreatable.html. Accessed 6 Dec 2014.

  15. Walsh CT, Wencewicz TA. Prospects for new antibiotics: a molecule-centered perspective. J Antibiotics. 2014;67:7–22.

    Article  CAS  Google Scholar 

  16. Davies J. Where have all the antibiotics gone? Can J Infect Dis Med Microbiol. 2006;17:287–90.

    PubMed  PubMed Central  Google Scholar 

  17. Walsh C. Where will new antibiotics come from? Nat Rev Microbiol. 2003;1:65–70.

    Article  CAS  PubMed  Google Scholar 

  18. Silver LL. Challenges of antibacterial discovery. Clin Microbiol Rev. 2011;24:71–109.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Schatz A, Bugie E, Waksman SA. Streptomycin, a substance exhibiting antibiotic activity against gram-positive and gram-negative bacteria. Proc Soc Exptl Biol Med. 1944;55:66–9.

    Article  CAS  Google Scholar 

  20. Umezawa S, Tsuchiya T. Total synthesis and chemical modification of the aminoglycoside antibiotics. In: Umezawa H, Hooper IR, editors. Aminoglycoside antibiotics. Berlin: Springer; 1982. p. 37–110.

    Chapter  Google Scholar 

  21. BerlinWaitz JA, Moss Jr E, Drube CG, Weinstein MJ. Comparative activity of sisomicin, gentamicin, kanamycin, and tobramycin. Antimicrob Agents Chemother. 1972;2:431–7.

    Article  Google Scholar 

  22. Vakulenko SB, Mobashery S. Versatility of aminoglycosides and prospects for their future. Clin Microbiol Rev. 2003;16:430–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Hermann T. Aminoglycoside antibiotics: old drugs and new therapeutic approaches. Cell Mol Life Sci. 2007;64:1841–52.

    Article  CAS  PubMed  Google Scholar 

  24. Reynolds AV, Hamilton-Miller JM, Brumfitt W. Newer aminoglycosides--amikacin and tobramycin: an in-vitro comparison with kanamycin and gentamicin. Br Med J. 1974;3:778–870.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Nelson ML, Levy SB. The history of the tetracyclines. Ann NY Acad Sci. 2011;241:17–32.

    Article  Google Scholar 

  26. Zhanel GG, Homenuik K, Nichol K, et al. The glycylcyclines: a comparative review with the tetracyclines. Drugs. 2004;64:63–88.

    Article  CAS  PubMed  Google Scholar 

  27. Andersson MI, MacGowan AP. Development of the quinolones. J Antimicrob Chemother. 2003;51(Suppl S1):1–11.

    Article  CAS  PubMed  Google Scholar 

  28. Hoshino K, Kitamura A, Morrissey I, et al. Comparison of inhibition of Escherichia coli topoisomerase IV by quinolones with DNA gyrase inhibition. Antimicrob Agents Chemother. 1994;38:2623–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Van Bambeke F, Michot JM, Van Eldere J, Tulkens PM. Quinolones in 2005: an update. Clin Microbiol Infect. 2005;11:256–80.

    Article  PubMed  Google Scholar 

  30. Fleischmann RD, Adams MD, White O, et al. Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science. 1995;269:496–512.

    Article  CAS  PubMed  Google Scholar 

  31. Mori H. From the sequence to cell modeling: comprehensive functional genomics in Escherichia coli. J Biochem Mol Biol. 2004;37:83–92.

    CAS  PubMed  Google Scholar 

  32. Pucci MJ. Novel genetic techniques and approaches in the microbial genomics era: identification and/or validation of targets for the discovery of new antibacterial agents. Drugs R D. 2007;8:201–12.

    Article  CAS  PubMed  Google Scholar 

  33. Hensel M, Shea JE, Gleeson C, et al. Simultaneous identification of bacterial virulence genes by negative selection. Science. 1995;269:400–3.

    Article  CAS  PubMed  Google Scholar 

  34. Slauch JM, Mahan MJ, Mekalanos JJ. In vivo expression technology for selection of bacterial genes specifically induced in host tissues. Methods Enzymol. 1994;235:481–92.

    Article  CAS  PubMed  Google Scholar 

  35. Pucci MJ. Use of genomics to select antibacterial targets. Biochem Pharmacol. 2006;71:1066–72.

    Article  CAS  PubMed  Google Scholar 

  36. Payne DJ, Gwynn MN, Holmes DJ, Pompliano DL. Drugs for bad bugs: confronting the challenges of antibacterial discovery. Nat Rev Drug Discov. 2007;6:29–40.

    Article  CAS  PubMed  Google Scholar 

  37. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 2001;46:3–26.

    Article  CAS  PubMed  Google Scholar 

  38. DeVito JA, Mills JA, Liu VG, et al. An array of target-specific screening strains for antibacterial discovery. Nat Biotechnol. 2002;20:478–83.

    Article  CAS  PubMed  Google Scholar 

  39. Brötz-Oesterhelt H, Sass P. Postgenomic strategies in antibacterial drug discovery. Future Microbiol. 2010;5:1553–79.

    Article  PubMed  Google Scholar 

  40. Rice L. Federal funding for the study of antimicrobial resistance in nosocomial pathogens: no ESKAPE. J Infect Dis. 2008;197:1079–81.

    Article  PubMed  Google Scholar 

  41. Boucher H, Talbot GH, Bradley JS. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin Infect Dis. 2009;48:1–12.

    Article  PubMed  Google Scholar 

  42. Spellberg B, Lipsky BA. Systemic antibiotic therapy for chronic osteomyelitis in adults. Clin Infect Dis. 2012;54:393–407.

    Article  PubMed  Google Scholar 

  43. Nordman P, Cuzon G, Naas T. The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria. Lancet Infect Dis. 2009;9:228–36.

    Article  Google Scholar 

  44. Dortet L, Poirel L, Nordman P. Worldwide dissemination of the NDM-type carbapenemases in gram-negative bacteria. BioMed Res Int. 2014. Article ID 249856.

    Google Scholar 

  45. Evans BA, Amyes SGB. OXA beta-lacatamases. Clin Microbiol Rev. 2014;27:241–63.

    Article  PubMed  PubMed Central  Google Scholar 

  46. David MZ, Daum RS. Community-associated methicillin-resistant Staphylococcus aureus: epidemiology and clinical consequences of an emerging epidemic. Clin Microbiol Rev. 2010;23:613–87.

    Article  Google Scholar 

  47. Doyle Y, Park YS, Rivera JI. Community-associated Extended-Spectrum β-Lactamase–producing Escherichia coli infection in the United States. Clin Inf Dis. 2013;56:641–8.

    Article  Google Scholar 

  48. Unemo M, Nicholas RA. Emergence of multidrug-resistant, extensively drug-resistant and untreatable gonorrhea. Future Microbiol. 2012;7:1401–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Projan S. Why is big Pharma getting out of antibacterial drug discovery? Curr Opin Microbiol. 2003;6:427–30.

    Article  PubMed  Google Scholar 

  50. White AR, Kaye C, Poupard J, et al. Augmentin® (amoxicillin/clavulanate) in the treatment of community-acquired respiratory tract infection: a review of the continuing development of an innovative antimicrobial agent. J Antimicrob Chemother. 2004;53:i3–i20.

    Article  CAS  PubMed  Google Scholar 

  51. Peters DH, Friedel HA, McTavish D. Azithromycin. A review of its antimicrobial activity, pharmacokinetic properties and clinical efficacy. Drugs. 1992;44:750–99.

    Article  CAS  PubMed  Google Scholar 

  52. Papp-Wallace KM, Endimiani A, Taracila MA, Bonomo RA. Carbapenems: past, present and future. Antimicrob Agents Chemother. 2011;55:4943–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Livermore DM. Discovery research: the scientific challenge of finding new antibiotics. J Antimicrob Chemother. 2011;66:1941–4.

    Article  CAS  PubMed  Google Scholar 

  54. Ledford H. FDA under pressure to relax drug rules. Nature. 2012;492:19.

    Article  CAS  PubMed  Google Scholar 

  55. Jarvis LM. A bacterial battle. Chem Eng News. 2014;92:9–14.

    Google Scholar 

  56. Sertkaya A, Eyraud J, Birkenbach A, Franz C, et al. 2014. Analytical framework for examining the value of antibacterial products. http://aspe.hhs.gov/sp/reports/2014/antibacterials/rpt_antibacterials.cfm. Accessed 20 Dec 2014.

  57. Staton T. It’s official: Gilead’s Sovaldi zooms past previous records with fastest-ever drug launch. Fierce Pharma Market. 2014;22:2014.

    Google Scholar 

  58. Mauldin PD, Salgado CD, Hansen IS, et al. Attributable hospital cost and length of stay associated with health care-associated infections caused by antibiotic-resistant gram-negative bacteria. Antimicrob Agents Chemother. 2010;54:109–15.

    Article  CAS  PubMed  Google Scholar 

  59. Spellberg B, Rex JH. The value of single-pathogen antibacterial agents. Nat Rev Drug Discov. 2013;12:963.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Murray PR, Masur H. Current approaches to the diagnosis of bacterial and fungal bloodstream infections for the ICU. Crit Care Med. 2012;40:3277–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. US Public law 112–144 (2012) www.gpo.gov/fdsys/pkg/PLAW-112publ144/pdf/PLAW-112publ144.pdf. Accessed 20 Dec 2014.

  62. Rex JH, Eisenstein BI, Alder J, Goldberger M, et al. A comprehensive regulatory framework to address the unmet need for new antibacterial treatments. Lancet Infect Dis. 2013;13:269–75.

    Article  PubMed  Google Scholar 

  63. Antibiotic Development to Advance Patient Treatment Act of 2013; 2013. www.hpm.com/pdf/blog/GINGRE_057_xml.pdf. Accessed 20 Dec 2014.

  64. Antibacterial Task Force: How CDER is establishing and promoting new approaches to antibacterial drug development. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/ucm406769.htm. Accessed 20 Dec 2014.

  65. December 4, 2014: Anti-infective drugs advisory committee meeting announcement (2014) www.fda.gov/AdvisoryCommittees/Calendar/ucm420134.htm. Accessed 20 Dec 2014.

  66. Rex JH. ND4BB: addressing the antimicrobial resistance crisis. Nat Rev Microbiol. 2014;12:231–2.

    Article  CAS  Google Scholar 

  67. Jarrett E. BARDA Broad Spectrum Antimicrobials (BSA) Program; 2014. http://www.phe.gov/ASPRBlog/Lists/Posts/Post.aspx?ID=97. Accessed 20 Dec 2014.

  68. NIAID antibacterial resistance program: current status and future directions; 2014. http://www.niaid.nih.gov/topics/antimicrobialResistance/documents/arstrategicplan2014.pdf. Accessed 20 Dec 2014.

  69. Plumridge H. Drug makers tiptoe back into antibiotic R&D. Wall Street J. January 23, 2014.

    Google Scholar 

  70. Merck to acquire cubist pharmaceuticals for $102 per share in cash. Company press release, December 8, 2014. http://www.merck.com/licensing/our-partnership/cubist-press-release.html.

  71. Boucher HW, Talbot GH, Benjamin Jr DK, et al. 10 × '20 Progress--development of new drugs active against gram-negative bacilli: an update from the Infectious Diseases Society of America. Clin Infect Dis. 2013;56:1685–94.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Pucci MJ, Bush K. Investigational antimicrobial agents of 2013. Clin Microbiol Rev. 2013;26:792–821.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Butler MS, Blaskovich MA, Cooper MA. Antibiotics in the clinical pipeline in 2013. J Antibiot (Tokyo). 2013;66:571–91.

    Article  CAS  Google Scholar 

  74. Drawz SM, Papp-Wallace KM, Bonomo RA. New β-lactamase inhibitors: a therapeutic renaissance in an MDR world. Antimicrob Agents Chemother. 2014;58:1835–46.

    Article  PubMed  PubMed Central  Google Scholar 

  75. The Pew Charitable Trusts. 2014. Antibiotics Currently in Clinical Development. http://www.pewtrusts.org/en/multimedia/data-visualizations/2014/antibiotics-currently-in-clinical-development. Accessed 11 Dec 2014.

  76. Prokocimer P, De Anda C, Fang E, et al. Tedizolid phosphate vs linezolid for treatment of acute bacterial skin and skin structure infections: the ESTABLISH-1 randomized trial. J Am Med Assoc. 2013;309:559–69.

    Article  CAS  Google Scholar 

  77. Moran GJ, Fang E, Corey GR, et al. Tedizolid for 6 days versus linezolid for 10 days for acute bacterial skin and skin-structure infections (ESTABLISH-2): a randomised, double-blind, phase 3, non-inferiority trial. Lancet Infect Dis. 2014;14:696–705.

    Article  CAS  PubMed  Google Scholar 

  78. Boucher HW, Wilcox M, Talbot GH, et al. Once-weekly dalbavancin versus daily conventional therapy for skin infection. N Engl J Med. 2014;370:2169–79.

    Article  PubMed  Google Scholar 

  79. Zhanel GG, Calic D, Schweizer F, et al. New lipoglycopeptides: a comparative review of dalbavancin, oritavancin and telavancin. Drugs. 2010;70:859–86.

    Article  CAS  PubMed  Google Scholar 

  80. Zhanel GG, Schweizer F, Karlowsky JA. Oritavancin: mechanism of action. Clin Infect Dis. 2012;54 Suppl 3:S214–9.

    Article  CAS  PubMed  Google Scholar 

  81. Corey GR, Good S, Jiang H, et al. Single-dose oritavancin versus 7–10 days of vancomycin in the treatment of gram-positive acute bacterial skin and skin structure infections: The SOLO II noninferiority study. Clin Infect Dis. 2014. pii: ciu778 [Epub ahead of print].

    Google Scholar 

  82. Corey GR, Kabler H, Mehra P, et al. Single-dose oritavancin in the treatment of acute bacterial skin infections. N Engl J Med. 2014;370:2180–90.

    Article  PubMed  Google Scholar 

  83. Farrell DJ, Flamm RK, Sader HS, Jones RN. Antimicrobial activity of ceftolozane-tazobactam tested against enterobacteriaceae and Pseudomonas aeruginosa with various resistance patterns isolated in U.S. hospitals (2011–2012). Antimicrob Agents Chemother. 2013;57:6305–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Popejoy MW, Cloutier D, Huntington JA, et al. Ceftolozane/tazobactam for the treatment of cUTI and cIAI caused by ESBL-producing Enterobacteriaceae. In: Paper presented at IDWeek, Philadelphia, 8-12 October 2014; 2014.

    Google Scholar 

  85. Actavis announces positive topline results from the Phase III program of ceftazidime-avibactam in patients with complicated intra-abdominal infections (cIAI). http://www.actavis.com/news/news/thomson-reuters/actavis-announces-positive-topline-results-from-th. Accessed 11 Dec 2014.

  86. FDA Division of Anti-Infective Products. Briefing package NDA 206494 ceftazidime-avibactam. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Anti-InfectiveDrugsAdvisoryCommittee/UCM425458.pdf. Accessed 11 Dec 2014.

  87. Castanheira M, Rhomberg PR, Watters A, Jones RN. In vitro activity of meropenem/RPX7009, a carbapenem/β-lactamase inhibitor combination tested against contemporary populations of Enterobacteriaceae and KPC-producing strains. In: Paper presented at IDWeek, Philadelphia, 8–12 October 2014; 2014.

    Google Scholar 

  88. Sabet M, Tarazi Z, Nolan T, et al. In Vivo Efficacy of Carbavance (meropenem/RPX7009) against KPC-producing Enterobacteriaceae. In: Paper presented at the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, 5–9 September 2014; 2014.

    Google Scholar 

  89. O'Riordan W, Mehra P, Manos P, et al. A randomized phase 2 study comparing two doses of delafloxacin with tigecycline in adults with complicated skin and skin-structure infections. Int J Infect Dis. 2014. pii: S1201-9712(14)01655-5. doi: 10.1016/j.ijid.2014.10.009 [Epub ahead of print].

  90. Longcor J, Hopkins S, Lawrence L et al (2012) Results of a phase 2 study of delafloxacin (DLX) compared to vancomycin (VAN) and linezolid (LNZ) in acute bacterial skin and skin structure infections (ABSSSI). In: Paper presented at the 52nd interscience conference on antimicrobial agents and chemotherapy, San Francisco, 9–12 September 2012.

    Google Scholar 

  91. Qin X, Huang H. Review of nemonoxacin with special focus on clinical development. Drug Des Devel Ther. 2014;8:765–74.

    CAS  PubMed  PubMed Central  Google Scholar 

  92. van Rensburg DJ, Perng RP, Mitha IH, et al. Efficacy and safety of nemonoxacin versus levofloxacin for community-acquired pneumonia. Antimicrob Agents Chemother. 2010;54:4098–106.

    Article  PubMed  PubMed Central  Google Scholar 

  93. Dong Wha Pharmaceuticals. Dong Wha completes Phase III study of quinolone antibacterial compound zabofloxacin; 2014. https://www.dong-wha.co.kr/english/customer/dnews/content.asp?t_idx=239. Accessed 11 Dec 2014.

  94. Tillotson G, Kim YS, Kim MJ, et al. Zabofloxacin for the treatment of mild to moderate community-acquired bacterial pneumonia compared to moxifloxacin; a phase 2 study. In: Paper presented at the 24th European Congress of Clinical Microbiology and Infectious Diseases, Barcelona, 10–13 May 2014; 2014.

    Google Scholar 

  95. Livermore DM, Mushtaq S, Warner M, et al. Activity of aminoglycosides, including ACHN-490, against carbapenem-resistant enterobacteriaceae isolates. J Antimicrob Chemother. 2011;66:48–53.

    Article  CAS  PubMed  Google Scholar 

  96. Solomkin JS, Ramesh MK, Cesnauskas G, et al. Phase 2, randomized, double-blind study of the efficacy and safety of two dose regimens of eravacycline versus ertapenem for adult community-acquired complicated intra-abdominal infections. Antimicrob Agents Chemother. 2014;58:1847–54.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Tetraphase Pharmaceuticals. Tetraphase Pharmaceuticals announces positive oral dosing data from lead-in of IGNITE 2 Phase 3 trial of eravacycline in cUTI support advancement to pivotal portion; 2014. http://ir.tphase.com/releasedetail.cfm?ReleaseID=868654. Accessed 11 Dec 2014.

  98. Biedenbach DJ, Castanheira M, Jones RN (2012) Activity of the fluoroketolide, solithromycin tested against bacterial species associated with significant community-acquired bacterial pneumonia and other gram-positive organisms. In: Paper presented at IDWeek, San Diego, 17–21 October 2012

    Google Scholar 

  99. Locher HH, Seiler P, Chen X, et al. In vitro and in vivo antibacterial evaluation of cadazolid, a new antibiotic for treatment of Clostridium difficile infections. Antimicrob Agents Chemother. 2014;58:892–900.

    Article  PubMed  PubMed Central  Google Scholar 

  100. Louie TJ, Buitrago M, Cornely OA et al (2013) Multicentre, double-blind, randomised, phase 2 study evaluating the novel antibiotic, cadazolid, in subjects with Clostridium difficile-associated diarrhea. In: Paper presented at the 53rd European Congress of Clinical Microbiology and Infectious Diseases, Berlin, 27–30 April 2013

    Google Scholar 

  101. DIFICID Prescribing Information 2014. http://www.dificid.com/downloads/Dificid_PI.pdf. Accessed 11 Dec 2014

  102. Mascio CTM, Mortin LI, Howland KT, et al. In Vitro and In Vivo characterization of CB-183,315, a novel lipopeptide antibiotic for treatment of Clostridium difficile. Antimicrob Agents Chemother. 2012;56:5023–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Shionogi & Co., Ltd. Shionogi presents pre-clinical and Phase 1 results for S-649266, a novel siderophore cephalosporin antibiotic with potential to treat multidrug-resistant gram-negative pathogens; 2014. http://www.prnewswire.com/news-releases/shionogi-presents-pre-clinical-and-phase-i-results-for-s-649266-a-novel-siderophore-cephalosporine-antibiotic-with-potential-to-treat-multidrug-resistant-gram-negative-pathogens-274336081.html. Accessed 11 Dec 2014.

  104. Jacobsson S, Golparian D, Alm RA, et al. High in-vitro activity of the novel spiropyrimidinetrione AZD0914, a DNA gyrase inhibitor, against multidrug resistant Neisseria gonorrhoeae isolates suggests a new effective option for oral treatment of gonorrhea. Antimicrob Agent Chemother. 2014;58:5585–8.

    Article  Google Scholar 

  105. Noel GJ, Draper MP, Hait H, et al. A randomized, evaluator-blind, phase 2 study comparing the safety and efficacy of omadacycline to those of linezolid for treatment of complicated skin and skin structure infections. Antimicrob Agents Chemother. 2012;56:5650–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Paratek Pharmaceuticals. http://www.paratekpharm.com/content/aboutus/index.htm. Accessed 11 Dec 2014.

  107. Prince WT, Ivezic-Schoenfeld Z, Lell C, et al. Phase II clinical study of BC-3781, a pleuromutilin antibiotic, in treatment of patients with acute bacterial skin and skin structure infections. Antimicrob Agents Chemother. 2013;57:2087–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Nabriva Therapeutics. Nabriva Therapeutics announces Qualified Infectious Disease Product and Fast Track status granted by the FDA for lefamulin; 2014. http://www.nabriva.com/news-publications/press-releases/fast-track/. Accessed 11 Dec 2014

  109. Craft JC, Moriarty SR, Clark K, et al. A randomized, double-blind phase 2 study comparing the efficacy and safety of an oral fusidic acid loading-dose regimen to oral linezolid for the treatment of acute bacterial skin and skin structure infections. Clin Infect Dis. 2011;52 Suppl 7:S520–6.

    Article  CAS  PubMed  Google Scholar 

  110. Cellceutix Corporation (2014) Cellceutix announces positive top-line data from Phase 2b ABSSSI trial; single-dose brilacidin comparable to 7-days of daptomycin. http://cellceutix.com/cellceutix-announces-positive-top-line-data-from-phase-2b-absssi-trial-single-dose-brilacidin-comparable-to-7-days-of-daptomycin/#sthash.SpaWi7VQ.XuEVN9NE.dpbs. Accessed 11 Dec 2014.

  111. Corey R, Naderer OJ, O'Riordan WD, et al. Safety, tolerability, and efficacy of GSK1322322 in the treatment of acute bacterial skin and skin structure infections. Antimicrob Agents Chemother. 2014;58:6518–27.

    Article  PubMed  PubMed Central  Google Scholar 

  112. Goldstein EJ, Citron DM, Tyrrell KL, Merriam CV. Comparative in vitro activities of SMT19969, a new antimicrobial agent, against Clostridium difficile and 350 gram-positive and gram-negative aerobic and anaerobic intestinal flora isolates. Antimicrob Agents Chemother. 2013;57:4872–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

The authors wish to acknowledge David Shlaes and Steven Projan who wrote the first version of this chapter entitled “Antimicrobial Resistance vs. the Discovery and Development of New Antimicrobials,” published in 2009 by the same editor. Their contribution represented a very useful starting point. We also would like to thank Olga Lomovskaya and Doug Mayers for their kind review and editorial comments.

Author information

Authors and Affiliations

  1. Tetraphase Pharmaceuticals, Watertown, MA, USA

    Jacques Dumas Ph.D.

  2. Spero Therapeutics, Cambridge, MA, USA

    Michael J. Pucci Ph.D.

  3. Biology, The Medicines Company, Saint-Laurent, QC, Canada

    Greg Moeck Ph.D.

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  1. Jacques Dumas Ph.D.
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  2. Michael J. Pucci Ph.D.
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  3. Greg Moeck Ph.D.
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Corresponding author

Correspondence to Jacques Dumas Ph.D. .

Editor information

Editors and Affiliations

  1. Treiber Therapeutics, Cambridge, Massachusetts, USA

    Douglas L. Mayers

  2. Wayne State University School of Medicine, Detroit Medical Center, Detroit, Michigan, USA

    Jack D. Sobel

  3. Centre de recherche en Infectiologie, University of Laval, Quebec City, Canada

    Marc Ouellette

  4. Division of Infectious Diseases, University of Michigan Medical School, Ann Arbor, Michigan, USA

    Keith S. Kaye

  5. Infection Control and Prevention Unit of Infectious Diseases, Assaf Harofeh Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel

    Dror Marchaim

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Dumas, J., Pucci, M.J., Moeck, G. (2017). Drug Development for Drug-Resistant Pathogens. In: Mayers, D., Sobel, J., Ouellette, M., Kaye, K., Marchaim, D. (eds) Antimicrobial Drug Resistance. Springer, Cham. https://doi.org/10.1007/978-3-319-46718-4_4

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