Antibiotics in late clinical development

Biochemical Pharmacology

Volumn 133, Issue , 2017, Pages 152-163

  Fernandes, Prabhavathi ^a   Martens, Evan ^a  

^a Cempra Pharmaceuticals Inc   (United States)

Author keywords

ABSSSI (acute bacterial skin and skin structure infections); Antibiotic development; CABP (community acquired bacterial pneumonia); cIAI (complicated intra abdominal infection); cUTI (complicated urinary tract infection); New antibiotics

Indexed keywords

AMINOGLYCOSIDE ANTIBIOTIC AGENT; ANTIBIOTIC AGENT; AVIBACTAM PLUS CEFTAZIDIME; BETA LACTAM ANTIBIOTIC; BETA LACTAMASE INHIBITOR; CARBAPENEMASE INHIBITOR; CEFTAROLINE FOSAMIL; CEFTOLOZANE PLUS TAZOBACTAM; CEPHALOSPORIN DERIVATIVE; CEPHALOSPORINASE INHIBITOR; DALBAVANCIN; DELAFLOXACIN; FATTY ACID SYNTHASE INHIBITOR; FOSFOMYCIN; FUSIDANE; GYRASE INHIBITOR; LEFAMULIN; MACROLIDE; NEMONOXACIN; ORITAVANCIN; OXAZOLIDINONE DERIVATIVE; PEPTIDOMIMETIC AGENT; PLAZOMICIN; PLEUROMUTILIN ANTIBIOTIC AGENT; QUINOLINE DERIVED ANTIINFECTIVE AGENT; RAMOPLANIN; TEDIZOLID; TETRACYCLINE DERIVATIVE; UNCLASSIFIED DRUG; UNINDEXED DRUG; ZABOFLOXACIN; ANTIINFECTIVE AGENT;

ANTIMICROBIAL ACTIVITY; DRUG APPROVAL; DRUG RESEARCH; FUNDING; HUMAN; PRIORITY JOURNAL; REVIEW; ANIMAL; DRUG DEVELOPMENT; DRUG INDUSTRY; ECONOMICS; PROCEDURES; SYNTHESIS; TRENDS;

ANIMALS; ANTI-BACTERIAL AGENTS; DRUG DISCOVERY; DRUG INDUSTRY; HUMANS;

EID: 85002202416     PISSN: 00062952     EISSN: 18732968     Source Type: Journal    
DOI: 10.1016/j.bcp.2016.09.025     Document Type: Review

References (59)

1. [1] Fernandes, P., Antibacterial discovery and development—the failure of success?. Nat. Biotechnol. 24:12 (2006), 1497–1503.
2. [2] O'Neill, J., Tackling drug-resistant infections globally: final report and recommendations. Rev. Antimicrob. Resist., 2016.
3. [3] Report to the President on Combating Antibiotic Resistance, Executive Office of the President. President's Council of Advisors on Science and Technology, September 2014.
4. [4] Centers for Disease Control and Prevention (CDC), Antibiotic Resistance Threats in the United States, 2013, http://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf (Accessed August 2016).
5. [5] Corey, R., Naderer, O.J., O'Riordan, W.D., Dumont, E., Jones, L.S., Kurtinecz, M., Zhu, J.Z., Safety, tolerability, and efficacy of GSK1322322 in the treatment of acute bacterial skin and skin structure infections. Antimicrob. Agents Chemother. 58:11 (2014), 6518–6527.
6. [6] Ling, L.L., Schneider, T., Peoples, A.J., Spoering, A.L., Engels, I., Conlon, B.P., Mueller, A., Schaberle, T.F., Hughes, D.E., Epstein, S., Jones, M., Lazarides, L., Steadman, V.A., Cohen, D.R., Felix, C.R., Fetterman, K.A., Millett, W.P., Nitti, A.G., Zullo, A.M., Chen, C., Lewis, K., A new antibiotic kills pathogens without detectable resistance. Nature 517:7535 (2015), 455–459.
7. [7] Taber, D., Total synthesis of the tetracyclines. Org. Chem. Highlights, 2005 http://www.organic-chemistry.org/Highlights/2005/07November.shtm (accessed August 2016).
8. [8] Seiple, I.B., Zhang, Z., Jakubec, P., Langlois-Mercier, A., Wright, P.M., Hog, D.T., Yabu, K., Allu, S.R., Fukuzaki, T., Carlsen, P.N., Kitamura, Y., Zhou, X., Condakes, M.L., Szczypinski, F.T., Green, W.D., Myers, A.G., A platform for the discovery of new macrolide antibiotics. Nature 533:7603 (2016), 338–345.
9. [9] Das, A., Khosla, C., Biosynthesis of aromatic polyketides in bacteria. Acc. Chem. Res. 42:5 (2009), 631–639.
10. [10] Cane, D.E., Nature as organic chemist. J. Antibiot. 69:7 (2016), 473–485.
11. [11] Blum, M.D., Graham, D.J., McCloskey, C.A., Temafloxacin syndrome: review of 95 cases. Clin. Infect. Dis. 18:6 (1994), 946–950.
12. [12] Shaw, P.J., Ganey, P.E., Roth, R.A., Idiosyncratic drug-induced liver injury and the role of inflammatory stress with an emphasis on an animal model of trovafloxacin hepatotoxicity. Toxicol. Sci. 118:1 (2010), 7–18.
13. [13] Ross, D.B., The FDA and the case of Ketek. N. Eng. J. Med. 356:16 (2007), 1601–1604.
14. [14] Food and Drug Administration (FDA), Guidance for Industry, Acute Bacterial Sinusitis: Developing Drugs for Treatment, October 2012, < http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070939.pdf>.
15. [15] Association for Professionals in Infection Control and Epidemiology (APIC), Antimicrobial Stewardship, < http://www.apic.org/Professional-Practice/Practice-Resources/Antimicrobial-Stewardship> (accessed 9.15.2016).
16. [16] Infectious Diseases Society of America (IDSA), Promoting Antimicrobial Stewardship in Human Medicine, < https://www.idsociety.org/Stewardship_Policy/> (accessed 9.15.2016).
17. [17] Currie, C.J., Berni, E., Jenkins-Jones, S., Poole, C.D., Ouwens, M., Driessen, S., de Voogd, H., Butler, C.C., Morgan, C.L., Antibiotic treatment failure in four common infections in UK primary care 1991–2012: longitudinal analysis. Br. Med. J., 349, 2014, g5493.
18. [18] Zhanel, G.G., Lawson, C.D., Adam, H., Schweizer, F., Zelenitsky, S., Lagace-Wiens, P.R., Denisuik, A., Rubinstein, E., Gin, A.S., Hoban, D.J., Lynch, J.P. 3rd, Karlowsky, J.A., Ceftazidime-avibactam: a novel cephalosporin/beta-lactamase inhibitor combination. Drugs 73:2 (2013), 159–177.
19. [19] Watkins, R.R., Papp-Wallace, K.M., Drawz, S.M., Bonomo, R.A., Novel beta-lactamase inhibitors: a therapeutic hope against the scourge of multidrug resistance. Front. Microbiol., 4(392), 2013.
20. [20] Castanheira, M., Rhomberg, P.R., Flamm, R.K., Jones, R.N., Effect of the beta-lactamase inhibitor vaborbactam combined with meropenem against serine carbapenemase-producing Enterobacteriaceae. Antimicrob. Agents Chemother. 60:9 (2016), 5454–5458.
21. [21] Lapuebla, A., Abdallah, M., Olafisoye, O., Cortes, C., Urban, C., Landman, D., Quale, J., Activity of imipenem with relebactam against gram-negative pathogens from New York City. Antimicrob. Agents Chemother. 59:8 (2015), 5029–5031.
22. [22] Biedenbach, D.J., Kazmierczak, K., Bouchillon, S.K., Sahm, D.F., Bradford, P.A., In vitro activity of aztreonam-avibactam against a global collection of Gram-negative pathogens from 2012 and 2013. Antimicrob. Agents Chemother. 59:7 (2015), 4239–4248.
23. [23] Ito-Horiyama, T., Ishii, Y., Ito, A., Sato, T., Nakamura, R., Fukuhara, N., Tsuji, M., Yamano, Y., Yamaguchi, K., Tateda, K., Stability of novel siderophore cephalosporin S-649266 against clinically relevant carbapenemases. Antimicrob. Agents Chemother. 60:7 (2016), 4384–4386.
24. [24] Page, M.G., Dantier, C., Desarbre, E., In vitro properties of BAL30072, a novel siderophore sulfactam with activity against multiresistant gram-negative bacilli. Antimicrob. Agents Chemother. 54:6 (2010), 2291–2302.
25. [25] Amunts, A., Brown, A., Toots, J., Scheres, S.H., Ramakrishnan, V., The structure of the human mitochondrial ribosome. Science 348:6230 (2015), 95–98.
26. [26] Garcia-Salguero, C., Rodriguez-Avial, I., Picazo, J.J., Culebras, E., Can plazomicin alone or in combination be a therapeutic option against carbapenem-resistant Acinetobacter baumannii?. Antimicrob. Agents Chemother. 59:10 (2015), 5959–5966.
27. [27] Davidovich, C., Bashan, A., Auerbach-Nevo, T., Yaggie, R.D., Gontarek, R.R., Yonath, A., Induced-fit tightens pleuromutilins binding to ribosomes and remote interactions enable their selectivity. Proc. Natl. Acad. Sci. U.S.A. 104:11 (2007), 4291–4296.
28. [28] Sader, H.S., Biedenbach, D.J., Paukner, S., Ivezic-Schoenfeld, Z., Jones, R.N., Antimicrobial activity of the investigational pleuromutilin compound BC-3781 tested against Gram-positive organisms commonly associated with acute bacterial skin and skin structure infections. Antimicrob. Agents Chemother. 56:3 (2012), 1619–1623.
29. [29] Prince, W.T., Ivezic-Schoenfeld, Z., Lell, C., Tack, K.J., Novak, R., Obermayr, F., Talbot, G.H., 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. 57:5 (2013), 2087–2094.
30. [30] Chopra, I., Roberts, M., Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiol. Mol. Biol. Rev. 65:2 (2001), 232–260.
31. [31] Macone, A.B., Caruso, B.K., Leahy, R.G., Donatelli, J., Weir, S., Draper, M.P., Tanaka, S.K., Levy, S.B., In vitro and in vivo antibacterial activities of omadacycline, a novel aminomethylcycline. Antimicrob. Agents Chemother. 58:2 (2014), 1127–1135.
32. [32] Zhanel, G.G., Cheung, D., Adam, H., Zelenitsky, S., Golden, A., Schweizer, F., Gorityala, B., Lagace-Wiens, P.R., Walkty, A., Gin, A.S., Hoban, D.J., Karlowsky, J.A., Review of eravacycline, a novel fluorocycline antibacterial agent. Drugs 76:5 (2016), 567–588.
33. [33] Fernandes, P., Use of antibiotic core structures to generate new and useful macrolide antibiotics. Sánchez, S., Demain, A.L., (eds.) Antibiotics, Current Innovations and Future Trends, 2015, Caister Academic Press, Norfolk, UK, 375–393.
34. [34] Fernandes, P., Martens, E., Bertrand, D., Pereira, D., The solithromycin journey—it is all in the chemistry. Bioorg. Med. Chem., 2016, 10.1016/j.bmc.2016.08.035.
35. [35] Barrera, C.M., Mykietiuk, A., Metev, H., Nitu, M.F., Karimjee, N., Doreski, P.A., Mitha, I., Tanaseanu, C.M., Molina, J.M., Antonovsky, Y., Van Rensburg, D.J., Rowe, B.H., Flores-Figueroa, J., Rewerska, B., Clark, K., Keedy, K., Sheets, A., Scott, D., Horwith, G., Das, A.F., Jamieson, B., Fernandes, P., Oldach, D., Efficacy and safety of oral solithromycin versus oral moxifloxacin for treatment of community-acquired bacterial pneumonia: a global, double-blind, multicentre, randomised, active-controlled, non-inferiority trial (SOLITAIRE-ORAL). Lancet Infect. Dis. 16:4 (2016), 421–430.
36. [36] File, T.M. Jr., Rewerska, B., Vucinic-Mihailovic, V., Gonong, J.R., Das, A.F., Keedy, K., Taylor, D., Sheets, A., Fernandes, P., Oldach, D., Jamieson, B.D., SOLITAIRE-IV Pneumonia Team, SOLITAIRE-IV: a randomized, double-blind, multicenter study comparing the efficacy and safety of intravenous-to-oral solithromycin to intravenous-to-oral moxifloxacin for treatment of community-acquired bacterial pneumonia. Clin. Infect. Dis. 63:8 (2016), 1007–1016.
37. [37] Hook, E.W. III, Golden, M., Jamieson, B.D., Dixon, P.B., Harbison, H.S., Lowens, S., Fernandes, P., A Phase 2 trial of oral solithromycin 1200 mg or 1000 mg as single-dose oral therapy for uncomplicated gonorrhea. Clin. Infect. Dis. 61:7 (2015), 1043–1048.
38. [38] Keelan, J.A., Payne, M.S., Kemp, M.W., Ireland, D.J., Newnham, J.P., A new, potent, and placenta-permeable macrolide antibiotic, solithromycin, for the prevention and treatment of bacterial infections in pregnancy. Front. Immunol., 7(111), 2016.
39. [39] Bisacchi, G.S., Origins of the quinolone class of antibacterials: An expanded “discovery story”. J. Med. Chem. 58:12 (2015), 4874–4882.
40. [40] Nakada, N., Gmunder, H., Hirata, T., Arisawa, M., Mechanism of inhibition of DNA gyrase by cyclothialidine, a novel DNA gyrase inhibitor. Antimicrob. Agents Chemother. 38:9 (1994), 1966–1973.
41. [41] So, W., Crandon, J.L., Nicolau, D.P., Pharmacodynamic profile of GSK2140944 against methicillin-resistant Staphylococcus aureus in a murine lung infection model. Antimicrob. Agents Chemother. 59:8 (2015), 4956–4961.
42. [42] Foerster, S., Golparian, D., Jacobsson, S., Hathaway, L.J., Low, N., Shafer, W.M., Althaus, C.L., Unemo, M., Genetic resistance determinants, in vitro time-kill curve analysis and pharmacodynamic functions for the novel topoisomerase II inhibitor ETX0914 (AZD0914) in Neisseria gonorrhoeae. Front. Microbiol., 6(1377), 2015.
43. [43] De Ambrogi, M., McConnell, J., Mushtaq, A., Highlights from the 26th ECCMID. Lancet Infect. Dis. 16:6 (2016), 645–647.
44. [44] Gerding, D.N., Hecht, D.W., Louie, T., Nord, C.E., Talbot, G.H., Cornely, O.A., Buitrago, M., Best, E., Sambol, S., Osmolski, J.R., Kracker, H., Locher, H.H., Charef, P., Wilcox, M., Susceptibility of Clostridium difficile isolates from a Phase 2 clinical trial of cadazolid and vancomycin in C. difficile infection. J. Antimicrob. Chemother. 71:1 (2016), 213–219.
45. [45] Chuanchuen, R., Beinlich, K., Hoang, T.T., Becher, A., Karkhoff-Schweizer, R.R., Schweizer, H.P., Cross-resistance between triclosan and antibiotics in Pseudomonas aeruginosa is mediated by multidrug efflux pumps: exposure of a susceptible mutant strain to triclosan selects nfxB mutants overexpressing MexCD-OprJ. Antimicrob. Agents Chemother. 45:2 (2001), 428–432.
46. [46] Karlowsky, J.A., Kaplan, N., Hafkin, B., Hoban, D.J., Zhanel, G.G., AFN-1252, a FabI inhibitor, demonstrates a Staphylococcus-specific spectrum of activity. Antimicrob. Agents Chemother. 53:8 (2009), 3544–3548.
47. [47] Yum, J.H., Kim, C.K., Yong, D., Lee, K., Chong, Y., Kim, C.M., Kim, J.M., Ro, S., Cho, J.M., In vitro activities of CG400549, a novel FabI inhibitor, against recently isolated clinical staphylococcal strains in Korea. Antimicrob. Agents Chemother. 51:7 (2007), 2591–2593.
48. [48] Sader, H.S., Fritsche, T.R., Jones, R.N., Potency and bactericidal activity of iclaprim against recent clinical gram-positive isolates. Antimicrob. Agents Chemother. 53:5 (2009), 2171–2175.
49. [49] Mensa, B., Howell, G.L., Scott, R., DeGrado, W.F., Comparative mechanistic studies of brilacidin, daptomycin, and the antimicrobial peptide LL16. Antimicrob. Agents Chemother. 58:9 (2014), 5136–5145.
50. [50] Vickers, R.J., Tillotson, G., Goldstein, E.J., Citron, D.M., Garey, K.W., Wilcox, M.H., Ridinilazole: a novel therapy for Clostridium difficile infection. Int. J. Antimicrob. Agents 48:2 (2016), 137–143.
51. [51] Fernandes, P., Fusidic acid: A bacterial elongation factor inhibitor for the oral treatment of acute and chronic staphylococcal infections. Silver, L.L., Bush, K., (eds.) Antibiotics and Antibiotic Resistance, 2016, Cold Spring Harbor Laboratory Press, New York, 355–371.
52. [52] Falagas, M.E., Giannopoulou, K.P., Kokolakis, G.N., Rafailidis, P.I., Fosfomycin: use beyond urinary tract and gastrointestinal infections. Clin. Infect. Dis. 46:7 (2008), 1069–1077.
53. [53] Obrecht, D., Robinson, J.A., Bernardini, F., Bisang, C., DeMarco, S.J., Moehle, K., Gombert, F.O., Recent progress in the discovery of macrocyclic compounds as potential anti-infective therapeutics. Curr. Med. Chem. 16:1 (2009), 42–65.
54. [54] Kali, A., Teixobactin: a novel antibiotic in treatment of gram-positive bacterial infections. J. Clin. Diagn. Res., 9(3), 2015, DL01.
55. [55] Zipperer, A., Konnerth, M.C., Laux, C., Berscheid, A., Janek, D., Weidenmaier, C., Burian, M., Schilling, N.A., Slavetinsky, C., Marschal, M., Willmann, M., Kalbacher, H., Schittek, B., Brotz-Oesterhelt, H., Grond, S., Peschel, A., Krismer, B., Human commensals producing a novel antibiotic impair pathogen colonization. Nature 535:7613 (2016), 511–516.
56. [56] Davidson, R., Cavalcanti, R., Brunton, J.L., Bast, D.J., de Azavedo, J.C., Kibsey, P., Fleming, C., Low, D.E., Resistance to levofloxacin and failure of treatment of pneumococcal pneumonia. N. Eng. J. Med. 346:10 (2002), 747–750.
57. [57] Rex, J.H., Outterson, K., Antibiotic reimbursement in a model delinked from sales: a benchmark-based worldwide approach. Lancet Infect. Dis. 16:4 (2016), 500–505.
58. [58] Balasegaram, M., Clift, C., Røttingen, J.-A., A pathway towards an alternative business model for antibiotic innovation: a framework, fund and institutional mechanism. J Law Med. Ethics (Special Supplement) 43:2 (2015), 22–26.
59. [59] Brogan, D.M., Mossialos, E., Incentives for new antibiotics: the Options Market for Antibiotics (OMA) model. Global. Health, 9, 2013, 58.