Antibiotics in the clinical pipeline in 2011

Journal of Antibiotics

Volumn 64, Issue 6, 2011, Pages 413-425

  Butler, Mark S ^a   Cooper, Matthew A ^a  

^a UNIVERSITY OF QUEENSLAND   (Australia)

Author keywords

clinical trials; drug development; drug discovery; natural product; resistance

Indexed keywords

5 FLUORO 1,3 DIHYDRO 2,1 BENZOXABOROL 1 OL; 6,7 DIHYDRO 2 NITRO 6 (4 TRIFLUOROMETHOXYBENZYLOXY) 5H IMIDAZO[2,1 B][1,3]OXAZINE; A 40926; ACHN 490; ACT 179811; AFN 1252; AMADACYCLINE; AN 3365; ANTIBIOTIC AGENT; ANTOFLOXACIN; API 1252; AZD 5847; AZD 9742; BAL 30072; BALOFLOXACIN; BAY 353377; BC 3205; BC 3781; BC 7013; BEDAQUILINE; BESIFLOXACIN; BIAPENEM; CB 183315; CEFTAROLINE FOSAMIL; CEFTOBIPROLE MEDOCARIL; CETHROMYCIN; CG 400549; CXA 101; DA 7218; DALBAVANCIN; DAPTOMYCIN; DELAFLOXACIN; DELAMANID; DORIPENEM; ERTAPENEM; FAB 001; FIDAXOMICIN; FR 264205; GARENOXACIN; GEMIFLOXACIN; GSK 1322322; GSK 2251052; ICLAPRIM; JNJ Q2; LINEZOLID; MK 2764; MUT 056399; N (2 ADAMANTYL) N' GERANYLETHYLENEDIAMINE; NEMONOXACIN; NVC 422; OMADACYCLINE; ORITAVANCIN; PAZUFLOXACIN; PF 02341272; PMX 30063; PNU 100480; PRULIFLOXACIN; RADEZOLID; RAMOPLANIN; RETAPAMULIN; RO 482622; SITAFLOXACIN; SOLITHROMYCIN; TEBIPENEM PIVOXIL; TEDIZOLID; TELAVANCIN; TELITHROMYCIN; TIGECYCLINE; TP 434; UNCLASSIFIED DRUG; UNINDEXED DRUG; WAP 8294A2; XF 73; ZABOFLOXACIN;

ANTIBACTERIAL ACTIVITY; ANTIBIOTIC RESISTANCE; DRUG MECHANISM; DRUG SYNTHESIS; GRAM NEGATIVE BACTERIUM; MULTIDRUG RESISTANCE; PRIORITY JOURNAL; REVIEW;

ANTI-BACTERIAL AGENTS; DRUG DESIGN; DRUG DISCOVERY; DRUG RESISTANCE, MULTIPLE, BACTERIAL; GRAM-NEGATIVE BACTERIA; GRAM-NEGATIVE BACTERIAL INFECTIONS; HUMANS; MICROBIAL SENSITIVITY TESTS;

NEGIBACTERIA;

EID: 79959740064     PISSN: 00218820     EISSN: 18811469     Source Type: Journal    
DOI: 10.1038/ja.2011.44     Document Type: Review

References (212)

1. Shlaes, D. M. Antibiotics: the Perfect Storm (Springer: the Netherlands, 2010).
2. Walsh, C. Antibiotics: Actions, Origins, Resistance (ASM Press: Washington, DC, USA, 2003).
3. Butler, M. S. & Buss, A. D. Natural products - the future scaffolds for novel antibiotics? Biochem. Pharmacol. 71, 919-929 (2006).
4. Projan, S. J. Whither antibacterial drug discovery? Drug Discov. Today 13, 279-280 (2008).
5. Silver, L. L. A retrospective on the failures and successes of antibacterial drug discovery. IDrugs 8, 651-655 (2005).
6. Rice, L. B. Federal funding for the study of antimicrobial resistance in nosocomial pathogens: no ESKAPE. J. Infect. Dis. 197, 1079-1081 (2008).
7. Talbot, G. H. What is in the pipeline for Gram-negative pathogens? Expert Rev. Anti Infect. Ther. 6, 39-49 (2008).
8. Vergidis, P. I. & Falagas, M. E. New antibiotic agents for bloodstream infections. Int. J. Antimicrob. Agents 32, S60-S65 (2008).
9. Livermore, D. M. Has the era of untreatable infections arrived? J. Antimicrob. Chemother. 64, i29-i36 (2009).
10. Boucher, H. W. Challenges in anti-infective development in the era of bad bugs, no drugs: a regulatory perspective using the example of bloodstream infection as an indication. Clin. Infect. Dis. 50, S4-S9 (2010).
11. Trémolières, F., Cohen, R., Gauzit, R., Vittecoq, D. & Stahl, J. P. Save antibiotics! What can be done to prevent a forecasted disaster? Suggestions to promote the development of new antibiotics. Réanimation 19, 354-360 (2010).
12. Moellering, R. C. The problem of complicated skin and skin structure infections: the need for new agents. J. Antimicrob. Chemother. 65, iv3-iv8 (2010).
13. Hamad, B. The antibiotics market. Nat. Rev. Drug Discov. 9, 675-676 (2010).
14. Gwynn, M. N., Portnoy, A., Rittenhouse, S. F. & Payne, D. J. Challenges of antibacterial discovery revisited. Ann. N. Y. Acad. Sci. 1213, 5-19 (2010).
15. Payne, D. J., Gwynn, M. N., Holmes, D. J. & Pompliano, D. L. Drugs for bad bugs: confronting the challenges of antibacterial discovery. Nat. Rev. Drug Discov. 6, 29-40 (2007).
16. Morel, C. M. & Mossialos, E. Stoking the antibiotic pipeline. BMJ 340, 1115-1118 (2010).
17. Jones, D. The antibacterial lead discovery challenge. Nat. Rev. Drug Discov. 9, 751-752 (2010).
18. Moellering, R. C. Jr Discovering new antimicrobial agents. Int. J. Antimicrob. Agents 37, 2-9 (2011).
19. Jones, D. A guiding hand for antibiotics. Nat. Rev. Drug Discov. 10, 161-162 (2011).
20. Silver, L. L. Challenges of antibacterial discovery. Clin. Microbiol. Rev. 24, 71-109 (2011).
21. Infectious Diseases Society of America. The 10x'20 Initiative: pursuing a global commitment to develop 10 new antibacterial drugs by 2020. Clin. Infect. Dis. 50, 1081-1083 (2010).
22. Spellberg, B. Antibiotic Resistance: Promoting Critically Needed Antibiotic Research and Development and Appropriate Use ('Stewardship') of these Precious Drugs Infectious Diseases Society of America 〈http://www. idsociety.org/WorkArea/DownloadAsset.aspx?id=16656〉 ( 2010, accessed 4 April 2011).
23. Boucher, H. W. et al. Bad bugs, no drugs: no ESKAPE! An update from the infectious diseases society of America. Clin. Infect. Dis. 48, 1-12 (2009).
24. European Centre for Disease Prevention and Control/European Medicines Agency. European Centre for Disease Prevention and Control/European Medicines Agency Joint Technical Report. the Bacterial Challenge: Time to React 〈http://www.emea. europa.eu/pdfs/human/antimicrobial-resistance/EMEA- 576176-2009.pdf〉 (2009, accessed 4 April 2011).
25. O'Shea, R. & Moser, H. E. Physicochemical properties of antibacterial compounds: implications for drug discovery. J. Med. Chem. 51, 2871-2878 (2008).
26. Silver, L. L. Are natural products still the best source for antibacterial discovery? The bacterial entry factor. Expert Opin. Drug Discov. 3, 487-500 (2008).
27. Optimer Pharmaceuticals. Optimer Pharmaceuticals Completes New Drug Application for Fidaxomicin and Requests Priority Review from FDA (press release 18 November 2010) 〈http://www.optimerpharma.com/news.asp〉 (2010).
28. Optimer Pharmaceuticals. The New England Journal of Medicine Publishes Results of Fidaxomicin Phase 3 Trial Showing Significantly Lower Recurrence Rates and Improved Global Cure Rates Compared to Vancomycin in Patients with Clostridium difficile Infection (CDI) (press release 2 February 2011) 〈http://www.optimerpharma. com/news.asp〉 (2011).
29. Norén, T. in Clostridium difficile. Methods in Molecular Biology. Vol. 646 (eds Mullany, P. and Roberts, A.P.) 9-35 (Humana Press: Totowa, NJ, USA, 2010).
30. Bartlett, J. G. Clostridium difficile: progress and challenges. Ann. N. Y. Acad. Sci. 1213, 62-69 (2010).
31. Cartman, S. T., Heap, J. T., Kuehne, S. A., Cockayne, A. & Minton, N. P. The emergence of 'hypervirulence' in Clostridium difficile. Int. J. Med. Microbiol. 300, 387-395 (2010).
32. Johnson, A. P. New antibiotics for selective treatment of gastrointestinal infection caused by Clostridium difficile. Expert Opin. Ther. Pat. 20, 1389-1399 (2010).
33. Trial watch: phase III success for novel Clostridium difficile antibiotic. Nat. Rev. Drug Discov. 9, 260 (2010).
34. Louie, T., Miller, M., Donskey, C., Mullane, K. & Goldstein, E. J. C. Clinical outcomes, safety, and pharmacokinetics of OPT-80 in a phase 2 trial with patients with Clostridium difficile infection. Antimicrob. Agents Chemother. 53, 223-228 (2009).
35. McAlpine, J. B., Jackson, M., Karwowski, J., Theriault, R. J. & Hochlowski, J. (Abbott Laboratories) Tiacumicin compounds. US 4,918,174, April 17 (1990).
36. Hochlowski, J. E. et al. Tiacumicins, a novel complex of 18-membered macrolides. II. Isolation and structure determination. J. Antibiot. 40, 575-588 (1987).
37. Theriault, R. J. et al. Tiacumicins, a novel complex of 18-membered macrolide antibiotics. I. Taxonomy, fermentation and antibacterial activity. J. Antibiot. 40, 567-574 (1987).
38. Coronelli, C., White, R. J., Lancini, G. C. & Parenti, F. Lipiarmycin, a new antibiotic from Actinoplanes. II. Isolation, chemical, biological, and biochemical characterization. J. Antibiot. 28, 253-259 (1975).
39. Coronelli, C., Parenti, F., White, R. & Pagani, H. (Gruppo Lepetit S.p.A.) Lipiarmycin and its preparation. US 3,978,211, August 31 (1976).
40. Parenti, F., Pagani, H. & Beretta, G. Lipiarmycin, a new antibiotic from Actinoplanes. I. Description of the producer strain and fermentation studies. J. Antibiot. 28, 247-252 (1975).
41. Sergio, S., Pirali, G., White, R. & Parenti, F. Lipiarmycin, a new antibiotic from Actinoplanes. III. Mechanism of action. J. Antibiot. 28, 543-549 (1975).
42. Arnone, A., Nasini, G. & Cavalleri, B. Structure elucidation of the macrocyclic antibiotic lipiarmycin. J. Chem. Soc. Perkin Trans. 1, 1353-1359 (1987).
43. Cavalleri, B., Arnone, A., Di, M. E., Nasini, G. & Goldstein, B. P. Structure and biological activity of lipiarmycin B. J. Antibiot. 41, 308-315 (1988).
44. Omura, S. et al. Clostomicins, new antibiotics produced by Micromonospora echinospora subsp. armeniaca subsp. nov. I. Production, isolation, and physicochemical and biological properties. J. Antibiot. 39, 1407-1412 (1986).
45. Talpaert, M., Campagnari, F. & Clerici, L. Lipiarmycin, an antibiotic inhibiting nucleic acid polymerases. Biochem. Biophys. Res. Commun. 63, 328-334 (1975).
46. Sonenshein, A. L. & Alexander, H. B. Initiation of transcription in vitro is inhibited by lipiarmycin. J. Mol. Biol. 127, 55-72 (1979).
47. Sonenshein, A. L., Alexander, H. B., Rothstein, D. B. & Fisher, S. H. Lipiarmycin-resistant ribonucleic acid polymerase mutants of Bacillus subtilis. J. Bacteriol. 132, 73-79 (1977).
48. Tupin, A., Gualtieri, M., Leonetti, J.- P. & Brodolin, K. The transcription inhibitor lipiarmycin blocks DNA fitting into the RNA polymerase catalytic site. EMBO J. 29, 2527-2537 (2010).
49. Kurabachew, M. et al. Lipiarmycin targets RNA polymerase and has good activity against multidrug-resistant strains of Mycobacterium tuberculosis. J. Antimicrob. Chemother. 62, 713-719 (2008).
50. Nanotherapeutics. Nanotherapeutics Acquires Two Late Stage Clinical Programs for Alzheimer's Treatment and CDA Disease (press release 16 December 2009) 〈http:// www.nanotherapeutics.com/news-press-releases.php〉 (2009).
51. Cavalleri, B., Pagani, H., Volpe, G., Selva, E. & Parenti, F. A-16686, a new antibiotic from Actinoplanes. I. Fermentation, isolation and preliminary physico-chemical characteristics. J. Antibiot. 37, 309-317 (1984).
52. Pallanza, R., Berti, M., Scotti, R., Randisi, E. & Arioli, V. A-16686, a new antibiotic from Actinoplanes. II. Biological properties. J. Antibiot. 37, 318-324 (1984).
53. Ciabatti, R. et al. Ramoplanin (A-16686), a new glycolipodepsipeptide antibiotic. III. Structure elucidation. J. Antibiot. 42, 254-267 (1989).
54. Skelton, N. J. et al. Structure elucidation and solution conformation of the glycopeptide antibiotic ramoplanose (UK-71,903): a cyclic depsipeptide containing an antiparallel b-sheet and a b-bulge. J. Am. Chem. Soc. 113, 7522-7530 (1991).
55. Kettenring, J. K., Ciabatti, R., Winters, G., Tamborini, G. & Cavalleri, B. Ramoplanin (A-16686), a new glycolipodepsipeptide antibiotic. IV. Complete sequence determination by homonuclear 2D NMR spectroscopy. J. Antibiot. 42, 268-275 (1989).
56. Fang, X. et al. The mechanism of action of ramoplanin and enduracidin. Mol. BioSyst. 2, 69-76 (2006).
57. Breukink, E. & de Kruijff, B. Lipid II as a target for antibiotics. Nat. Rev. Drug Discov. 5, 321-323 (2006).
58. Schneider, T. & Sahl, H.- G. Lipid II and other bactoprenol-bound cell wall precursors as drug targets. Curr. Opin. Invest. Drugs 11, 157-164 (2010).
59. Hamburger, J. B. et al. A crystal structure of a dimer of the antibiotic ramoplanin illustrates membrane positioning and a potential lipid II docking interface. Proc. Natl. Acad. Sci. USA 106, 13759-13764 (2009).
60. Singley, C., Hoover, J., DeMarsh, P., Elefante, P. & Zalacain, M. Efficacy of PDF inhibitor GSK1322322 against abscess infections caused by MRSA using a computer-controlled infusion system to recreate human PK profiles in rats. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy Conference (Boston, MA), Poster F1-2114 (2010).
61. Lewandowski, T., Demarsh, P., Peters, T. & Kulkarni, S. Potent activity of GSK1322322 a novel peptide deformylase inhibitor after oral dosing in a murine multi-drug resistant Staphylococcus aureus infection. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy Conference (Boston, MA), Poster F1-2113 (2010).
62. Bouchillon, S., Hackel, M., Hoban, D., Zalacain, M. & Butler, D. In vitro activity of GSK1322322, a novel peptide deformylase inhibitor, against 4836 pathogens from skin and soft tissue infections and respiratory tract infections. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy Conference (Boston, MA), Poster F1-2112 (2010).
63. Lewandowski, T., Demarsh, P., Peters, T. & Kulkarni, S. Potent Activity of GSK1322322 a novel peptide deformylase inhibitor after oral dosing in a murine multi-drug resistant Staphylococcus aureus infection. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy Conference (Boston, MA), Poster F1-2113 (2010).
64. US National Institutes of Health. A GSK1322322 versus Linezolid in the Treatment of Acute Bacterial Skin and Skin Structure Infection (NCT01209078) US National Institutes of Health 〈http://clinicaltrials.gov/ct2/show/ NCT01209078〉 (accessed 4 April 2011).
65. Sharma, A., Khuller, G. K. & Sharma, S. Peptide deformylase - a promising therapeutic target for tuberculosis and antibacterial drug discovery. Expert Opin. Ther. Targets 13, 753-765 (2009).
66. Leeds, J. A. & Dean, C. R. Peptide deformylase as an antibacterial target: a critical assessment. Curr. Opin. Pharmacol. 6, 445-452 (2006).
67. Azoulay-Dupuis, E., Mohler, J. & Bedos, J. P. Efficacy of BB-83698, a novel peptide deformylase inhibitor, in a mouse model of pneumococcal pneumonia. Antimicrob. Agents Chemother. 48, 80-85 (2004).
68. Osborne, C. S. et al. In vivo characterization of the peptide deformylase inhibitor LBM415 in murine infection models. Antimicrob. Agents Chemother. 53, 3777-3781 (2009).
69. Waites, K. B., Reddy, N. B., Crabb, D. M. & Duffy, L. B. Comparative in vitro activities of investigational peptide deformylase inhibitor NVP LBM-415 and other agents against human mycoplasmas and ureaplasmas. Antimicrob. Agents Chemother. 49, 2541-2542 (2005).
70. Gordon, J. J., Kelly, B. K. & Miller, G. A. Actinonin: an antibiotic substance produced by an actinomycete. Nature 195, 701-702 (1962).
71. Gordon, J. J. et al. Studies concerning the antibiotic actinonin. Part I. The constitution of actinonin. A natural hydroxamic acid with antibiotic activity. J. Chem. Soc., Perkin Trans. 1, 819-825 (1975).
72. Chen, D. Z. et al. Actinonin, a naturally occurring antibacterial agent, is a potent deformylase inhibitor. Biochemistry 39, 1256-1262 (2000).
73. US National Institutes of Health. Study to Evaluate NVC-422 for Urinary Catheter Blockage and Encrustation (NCT01243125) US National Institutes of Health 〈http://clinicaltrials.gov/ct2/show/NCT01243125〉 (accessed 4 April 2011).
74. NovaBay Pharmaceuticals. NovaBay Pharmaceuticals Provides Summary of 2010 Accomplishments and 2011 Outlook. (press release 2 February 2011) 〈http:// www.novabaypharma.com/investors/release/Feb-2-2011〉 (2011).
75. Shiau, T. P. et al. Stieglitz rearrangement of N,N-dichloro-b,b- disubstituted taurines under mild aqueous conditions. Bioorg. Med. Chem. Lett. 19, 1110-1114 (2009).
76. Francavilla, C. et al. Quaternary ammonium N,N-dichloroamines as topical, antimicrobial agents. Bioorg. Med. Chem. Lett. 19, 2731-2734 (2009).
77. Wang, L., Khosrovi, B. & Najafi, R. N-Chloro-2,2-dimethyltaurines: a new class of remarkably stable N-chlorotaurines. Tetrahedron Lett. 49, 2193-2195 (2008).
78. Gottardi, W. & Nagl, M. N-chlorotaurine, a natural antiseptic with outstanding tolerability. J. Antimicrob. Chemother. 65, 399-409 (2010).
79. Zgliczyñski, J. M., Stelmaszyñsky, T., Domañski, J. & Ostrowski, W. Chloramines as intermediates of oxidation reaction of amino acids by myeloperoxidase. Biochim. Biophys. Acta Enzymol. 235, 419-424 (1971).
80. Stelmaszyñsky, T. & Zgliczyñski, J. M. Myeloperoxidase of human neutrophilic granulocytes as chlorinating enzyme. Eur. J. Biochem. 45, 305-312 (1974).
81. PolyMedix. PolyMedix Successfully Completes Phase 1 Exposure Escalation Safety Study with PMX-30063 Antibiotic (press release 24 February 2011) 〈http://www. polymedix.com/〉 (2011).
82. PolyMedix. PMX-30063 Antibiotic Fact Sheet (February 2011) 〈http://www.polymedix.com/pdf/PMX-30063factsheet.pdf〉 (accessed 4 April 2011).
83. Liu, D. et al. Nontoxic membrane-active antimicrobial arylamide oligomers. Angew. Chem. Int. Ed. 43, 1158-1162 (2004).
84. Choi, S. et al. De novo design and in vivo activity of conformationally restrained antimicrobial arylamide foldamers. Proc. Natl. Acad. Sci. USA 106, 6968-6973 (2009).
85. Scott, R. W. Defensin mimetics: nature knows best. Am. Biotechnol. Lab. 27, 16-19 (2009).
86. Tew, G. N., Scott, R. W., Klein, M. L. & DeGrado, W. F. De novo design of antimicrobial polymers, foldamers, and small molecules: from discovery to practical applications. Acc. Chem. Res. 43, 30-39 (2010).
87. Webb, S. Public-private partnership tackles TB challenges in parallel. Nat. Rev. Drug Discov. 8, 599-600 (2009).
88. Tibotec. Unique Collaboration between TB Alliance and Tibotec to Accelerate Tuberculosis Drug Development (press release 17 June 2009) 〈http://www.tibotec.com/ news/detail.jhtml?action=view&itemname=news- 62〉 (2009).
89. Diacon, A. H. et al. The diarylquinoline TMC207 for multidrug-resistant tuberculosis. N. Engl. J. Med. 360, 2397-2405 (2009).
90. Rustomjee, R. et al. Early bactericidal activity and pharmacokinetics of the diarylquinoline TMC207 in treatment of pulmonary tuberculosis. Antimicrob. Agents Chemother. 52, 2831-2835 (2008).
91. Andries, K. et al. A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science 307, 223-227 (2005).
92. Koul, A. et al. Diarylquinolines target subunit c of mycobacterial ATP synthase. Nat. Chem. Biol. 3, 323-324 (2007).
93. Koul, A. et al. Diarylquinolines are bactericidal for dormant mycobacteria as a result of disturbed ATP homeostasis. J. Biol. Chem. 283, 25273-25280 (2008).
94. Haagsma, A. C. et al. Selectivity of TMC207 towards mycobacterial ATP synthase compared with that towards the eukaryotic homologue. Antimicrob. Agents Chemother. 53, 1290-1292 (2009).
95. aRigen Pharmaceutical. WAP-8294A2 (Lotilibcin), a First-line Anti-MRSA Product Candidate: License Agreement Boosts Development of Novel Therapy Against MRSA Infection (aRigen press release 21 January 2011) 〈http://www.arigen. jp/main/ newsPR.htm〉 (2011).
96. Harada, K. et al. Separation of WAP-8294A components, a novel anti-methicillin-resistant Staphylococcus aureus antibiotic, using high-speed counter-current chromatography. J. Chromatogr. A 932, 75-81 (2001).
97. Ohashi, Y. et al. (Wakamoto Pharmacetical Co.) Antibiotics WAP-8294A, Method for Preparing the Same and Antibacterial Compositions. US 5,648,455 (1997).
98. Kato, A. et al. WAP-8294A2, a novel anti-MRSA antibiotic produced by Lysobacter sp. J. Am. Chem. Soc. 119, 6680-6681 (1997).
99. Kato, A. et al. A new anti-MRSA antibiotic complex, WAP-8294A I. Taxonomy, isolation and biological activities. J. Antibiot. 51, 929-935 (1998).
100. Destiny Pharma. Destiny Pharma present XF-73 Clinical Results at the 50th Annual ICAAC Meeting in Boston, USA (press release September 2010) 〈http://www.destinypharma.com/news-current.shtml〉 ( 2010, accessed 4 April 2011).
101. Maisch, T., Bosl, C., Szeimies, R. M., Lehn, N. & Abels, C. Photodynamic effects of novel XF porphyrin derivatives on prokaryotic and eukaryotic cells. Antimicrob. Agents Chemother. 49, 1542-1552 (2005).
102. Farrell, D. J., Robbins, M., Rhys-Williams, W. & Love, W. G. In vitro activity of XF-73, a novel antibacterial agent, against antibiotic-sensitive and -resistant Gram-positive and Gram-negative bacterial species. Int. J. Antimicrob. Agents 35, 531-536 (2010).
103. Ooi, N. et al. XF-73, a novel antistaphylococcal membrane-active agent with rapid bactericidal activity. J. Antimicrob. Chemother. 64, 735-740 (2009).
104. Ooi, N. et al. XF-70 and XF-73, novel antibacterial agents active against slow-growing and non-dividing cultures of Staphylococcus aureus including biofilms. J. Antimicrob. Chemother. 65, 72-78 (2010).
105. Farrell, D. J., Robbins, M., Rhys-Williams, W. & Love, W. G. Investigation of the potential for mutational resistance to XF-73, retapamulin, mupirocin, fusidic acid, daptomycin, and vancomycin in methicillin-resistant Staphylococcus aureus Isolates during a 55-passage study. Antimicrob. Agents Chemother. 55, 1177-1181 (2011).
106. US National Institutes of Health. An Open-Label, Randomized, Single Period, Parallel-Cohort Study to Evaluate Serum and Pulmonary Pharmacokinetics Following Single and Multiple Dose Administration of Intravenous GSK2251052 in Healthy Adult Subjects (NCT01267968) US National Institutes of Health 〈http://clinicaltrials. gov/ct2/show/NCT01267968〉 (accessed 4 April 2011).
107. US National Institutes of Health. A Randomized, Single Blind, Placebo Controlled Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Single Oral Doses and Repeat Escalating Oral Doses of GSK2251052 in Healthy Adult Subjects (NCT01262885) US National Institutes of Health 〈http://clinicaltrials.gov/ct2/ show/NCT01262885〉 (accessed 4 April 2011).
108. Hernandez, V. et al. Discovery and mechanism of action of AN3365: A novel Boron-containing antibacterial agent in clinical development for Gram-negative infections. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy Conference (Boston, MA), Poster F1-1637 (2010).
109. Hernandez, V. et al. Structure-guided discovery of ABX a 3-aminomethyl benzoxaborole: a first in class antibacterial for Gram-negative bacterial infections. Keystone Symposia: Antibiotics and Resistance: Challenges and Solutions (Santa Fe, NM) (2010).
110. Baker, S. J. et al. Discovery of a new Boron-containing antifungal agent, 5-fluoro-1,3- dihydro-1-hydroxy-2,1-benzoxaborole (AN2690), for the potential treatment of onychomycosis. J. Med. Chem. 49, 4447-4450 (2006).
111. Rock, F. L. et al. An antifungal agent inhibits an aminoacyl-tRNA synthetase by trapping tRNA in the editing site. Science 316, 1759-1761 (2007).
112. Seiradake, E. et al. Crystal structures of the human and fungal cytosolic leucyl-tRNA synthetase editing domains: a structural basis for the rational design of antifungal benzoxaboroles. J. Mol. Biol. 390, 196-207 (2009).
113. Karlowsky, J. A. et al. In vitro activity of API-1252, a novel FabI inhibitor, against clinical isolates of Staphylococcus aureus and Staphylococcus epidermidis. Antimicrob. Agents Chemother. 51, 1580-1581 (2007).
114. 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, 3544-3548 (2009).
115. Affinium Pharmaceuticals. Affinium Pharmaceuticals Programs Overview 〈http:// www.afnm.com/programs/〉 (accessed 4 April 2011).
116. Lu, H. & Tonge, P. J. Inhibitors of FabI, an enzyme drug target in the bacterial fatty acid biosynthesis pathway. Acc. Chem. Res. 41, 11-20 (2008).
117. Gerusz, V. in Annual Reports in Medicinal Chemistry Vol. 45 (ed Macor, E.J.) 295-311 (Academic Press: Burlington, MA, USA, 2010).
118. Payne, D. J. et al. Discovery of a novel and potent class of FabI-directed antibacterial agents. Antimicrob. Agents Chemother. 46, 3118-3124 (2002).
119. Medical News Today. FAB Pharma, a Biopharma Company Developing Drugs To Treat Severe Bacterial Infections 〈http://www.medicalnewstoday.com/ articles/164032.php〉 (2009, accessed 4 April 2011).
120. Yum, J. H. et al. In vitro activities of CG400549, a novel FabI inhibitor, against recently isolated clinical staphylococcal strains in Korea. Antimicrob. Agents Chemother. 51, 2591-2593 (2007).
121. Park, H. S. et al. Antistaphylococcal activities of CG400549, a new bacterial enoyl-acyl carrier protein reductase (FabI) inhibitor. J. Antimicrob. Chemother. 60, 568-574 (2007).
122. Bogdanovich, T. et al. Antistaphylococcal activity of CG400549, a new experimental FabI inhibitor, compared with that of other agents. Antimicrob. Agents Chemother. 51, 4191-4195 (2007).
123. Jungermann, E. & Taber, D. A new broad spectrum antibacterial soap I. General properties. J. Am. Oil Chem. Soc. 48, 318-323 (1971).
124. Russell, A. D. Whither triclosan? J. Antimicrob. Chemother. 53, 693-695 (2004).
125. Saleh, S., Haddadin, R. N. S., Baillie, S. & Collier, P. J. Triclosan - an update. Lett. Appl. Microbiol. 52, 87-95 (2011).
126. US Department of Health & Human Services. Ingredients: Triclosan, Household Products Database 〈http://householdproducts.nlm.nih.gov/cgi-bin/ household/brands? tbl=chem&id=201〉 (accessed 4 April 2011).
127. Ward, W. H. J. et al. Kinetic and structural characteristics of the inhibition of enoyl (acyl carrier protein) reductase by triclosan. Biochemistry 38, 12514-12525 (1999).
128. Stewart, M. J., Parikh, S., Xiao, G., Tonge, P. J. & Kisker, C. Structural basis and mechanism of enoyl reductase inhibition by triclosan. J. Mol. Biol. 290, 859-865 (1999).
129. Levy, C. W. et al. Molecular basis of triclosan activity. Nature 398, 383-384 (1999).
130. Xu, H. et al. Mechanism and inhibition of saFabI, the enoyl reductase from Staphylococcus aureus. Biochemistry 47, 4228-4236 (2008).
131. Gomez Escalada, M., Russell, A. D., Maillard, J. Y. & Ochs, D. Triclosan-bacteria interactions: single or multiple target sites? Lett. Appl. Microbiol. 41, 476-481 (2005).
132. Novak, R. & Shlaes, D. M. The pleuromutilin antibiotics: a new class for human use. Curr. Opin. Invest. Drugs 11, 182-191 (2010).
133. Wang, J. et al. A phase II study of antofloxacin hydrochloride, a novel fluoroquinolone, for the treatment of acute bacterial infections. Chemotherapy 56, 378-385 (2010).
134. Wang, J. et al. Pharmacokinetics of antofloxacin hydrochloride, a novel fluoroquinolone, after single-dose intravenous administration in healthy Chinese male volunteers. Xenobiotica 40, 344-349 (2010).
135. Shanghai Institute of Materia Medica. Antofloxacin Hydrochloride and its Tablets, a Class One New Drug, has been Granted New Drug License and Drug Approval Certificate (press release 23 June 2009) 〈http://english.simm.cas. cn/rp/200906/ t20090626-9128.html〉 ( 2009, accessed 4 April 2011).
136. Chung, J. Y. L., Hartner, F. W. & Cvetovich, R. J. Synthesis development of an aminomethylcycline antibiotic via an electronically tuned acyliminium Friedel-Crafts reaction. Tetrahedron Lett. 49, 6095-6100 (2008).
137. Wang, Y., Castaner, R., Bolos, J. & Estivill, C. Amadacycline: tetracycline antibiotic. Drugs Future 34, 11-15 (2009).
138. Im, W. B. et al. Discovery of torezolid as a novel 5-hydroxymethyl- oxazolidinone antibacterial agent. Eur. J. Med. Chem. 46, 1027-1039 (2011).
139. Brown, S. D. & Traczewski, M. M. Comparative in vitro antimicrobial activities of torezolid (TR-700), the active moiety of a new oxazolidinone, torezolid phosphate (TR- 701), determination of tentative disk diffusion interpretive criteria, and quality control ranges. Antimicrob. Agents Chemother. 54, 2063-2069 (2010).
140. Prokocimer, P. et al. Phase 2, randomized, double-blind, dose-ranging study evaluating the safety, tolerability, population pharmacokinetics, and efficacy of oral torezolid phosphate in patients with complicated skin and skin structure infections. Antimicrob. Agents Chemother. 55, 583-592 (2011).
141. Cooper, R. D. G. et al. Reductive alkylation of glycopeptide antibiotics: synthesis and antibacterial activity. J. Antibiot. 49, 575-581 (1996).
142. Bouza, E. & Burillo, A. Oritavancin: a novel lipoglycopeptide active against Gram-positive pathogens including multiresistant strains. Int. J. Antimicrob. Agents 36, 401-407 (2010).
143. Belley, A. et al. Oritavancin disrupts membrane integrity of Staphylococcus aureus and vancomycin-resistant enterococci to effect rapid bacterial killing. Antimicrob. Agents Chemother. 54, 5369-5371 (2010).
144. Allen, N. E. From vancomycin to oritavancin: the discovery and development of a novel lipoglycopeptide antibiotic. Anti-Infect. Agents Med. Chem. 9, 23-47 (2010).
145. Guskey, M. T. & Tsuji, B. T. A comparative review of the lipoglycopeptides: oritavancin, dalbavancin, and telavancin. Pharmacotherapy 30, 80-94 (2010).
146. Malabarba, A. et al. Amides of de-acetylglucosaminyl-deoxy teicoplanin active against highly glycopeptide-resistant enterococci. Synthesis and antibacterial activity. J. Antibiot. 47, 1493-1506 (1994).
147. Malabarba, A. & Goldstein, B. P. Origin, structure, and activity in vitro and in vivo of dalbavancin. J. Antimicrob. Chemother. 55, ii15-ii20 (2005).
148. Biedenbach, D. J., Bell, J. M., Sader, H. S., Turnidge, J. D. & Jones, R. N. Activities of dalbavancin against a worldwide collection of 81673 Gram-positive bacterial isolates. Antimicrob. Agents Chemother. 53, 1260-1263 (2009).
149. Sosio, M., Canavesi, A., Stinchi, S. & Donadio, S. Improved production of A40926 by Nonomuraea sp. through deletion of a pathway-specific acetyltransferase. Appl. Microbiol. Biotechnol. 87, 1633-1638 (2010).
150. Or, Y. S. et al. Design, synthesis, and antimicrobial activity of 6-O-substituted ketolides active against resistant respiratory tract pathogens. J. Med. Chem. 43, 1045-1049 (2000).
151. Ma, Z. et al. Novel erythromycin derivatives with aryl groups tethered to the C-6 position are potent protein synthesis inhibitors and active against multidrug-resistant respiratory pathogens. J. Med. Chem. 44, 4137-4156 (2001).
152. Hammerschlag, M. R. & Sharma, R. Use of cethromycin, a new ketolide, for treatment of community-acquired respiratory infections. Expert Opin. Invest. Drugs 17, 387-400 (2008).
153. Rafie, S., MacDougall, C. & James, C. L. Cethromycin: a promising new ketolide antibiotic for respiratory infections. Pharmacotherapy 30, 290-303 (2010).
154. Zeitlinger, M., Wagner, C. C. & Heinisch, B. Ketolides - the modern relatives of macrolides: the pharmacokinetic perspective. Clin. Pharmacokinet. 48, 23-38 (2009).
155. Endimiani, A. et al. ACHN-490, a neoglycoside with potent in vitro activity against multidrug-resistant Klebsiella pneumoniae isolates. Antimicrob. Agents Chemother. 53, 4504-4507 (2009).
156. Aggen, J. B. et al. Synthesis and spectrum of the neoglycoside ACHN-490. Antimicrob. Agents Chemother. 54, 4636-4642 (2010).
157. Armstrong, E. S. & Miller, G. H. Combating evolution with intelligent design: the neoglycoside ACHN-490. Curr. Opin. Microbiol. 13, 565-573 (2010).
158. US National Institutes of Health. Study Comparing the Safety and Efficacy of Two Doses of BC-3781 vs Vancomycin in Patients with Acute Bacterial Skin and Skin Structure Infection (ABSSSI) (NCT01119105) 〈http://clinicaltrials. gov/ct2/show/ NCT01119105〉 (accessed 4 April 2011).
159. Sader, H. S. et al. Activity of BC-3781, a novel pleuromutilin compound, tested against clinical isolates of MRSA, including molecularly characterized community-acquired and hospital-associated strains. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy Conference. (Boston, MA), Poster F1-2105 (2010).
160. Wicha, W. W., Ivezic-Schoenfeld, Z. & Novak, R. Efficacy of BC-3781 in murine pneumonia models. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy Conference. (Boston, MA), Poster F1-2107 (2010).
161. Yin, N. et al. Structure activity relationship studies of aromatic tail containing lipopeptides leading to CB-183315, a novel cyclic lipopeptide being developed for the treatment of Clostridium difficile infection. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy Conference. (Boston, MA), Poster F1-1612 (2010).
162. US National Institutes of Health. Study of CB-183315 in Patients with Clostridium Difficile Infection (NCT01085591) 〈http://clinicaltrials.gov/ ct2/show/ NCT01085591〉 (accessed 4 April 2011).
163. Hunt, D. et al. TP-434 is a novel broad-spectrum fluorocycline. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy Conference (Boston, MA), Poster F1-2157 (2010).
164. US National Institutes of Health. Study to Compare TP-434 and Ertapenem in CA Complicated Intra-abdominal Infections (NCT01265784) 〈http:// clinicaltrials.gov/ ct2/show/NCT01265784〉 (accessed 4 April 2011).
165. McGhee, P. et al. In vitro activity of CEM-101 against Streptococcus pneumoniae and Streptococcus pyogenes with defined macrolide resistance mechanisms. Antimicrob. Agents Chemother. 54, 230-238 (2009).
166. Woosley, L. N., Castanheira, M. & Jones, R. N. CEM-101 activity against Gram-positive organisms. Antimicrob. Agents Chemother. 54, 2182-2187 (2010).
167. Putnam, S. D., Sader, H. S., Farrell, D. J., Biedenbach, D. J. & Castanheira, M. Antimicrobial characterisation of solithromycin (CEM-101), a novel fluoroketolide: activity against staphylococci and enterococci. Int. J. Antimicrob. Agents 37, 39-45 (2011).
168. Putnam, S. D., Castanheira, M., Moet, G. J., Farrell, D. J. & Jones, R. N. CEM-101, a novel fluoroketolide: antimicrobial activity against a diverse collection of Grampositive and Gram-negative bacteria. Diagn. Microbiol. Infect. Dis. 66, 393-401 (2010).
169. Takeda, S., Nakai, T., Wakai, Y., Ikeda, F. & Hatano, K. In vitro and in vivo activities of a new cephalosporin, FR264205, against Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 51, 826-830 (2007).
170. Toda, A. et al. Synthesis and SAR of novel parenteral anti-pseudomonal cephalosporins: discovery of FR264205. Bioorg. Med. Chem. Lett. 18, 4849-4852 (2008).
171. Ge, Y., Whitehouse, M. J., Friedland, I. & Talbot, G. H. Pharmacokinetics and safety of CXA-101, a new antipseudomonal cephalosporin, in healthy adult male and female subjects receiving single- and multiple-dose intravenous infusions. Antimicrob. Agents Chemother. 54, 3427-3431 (2010).
172. US National Institutes of Health. ACT-179811 in Patients with Clostridium Difficile Infection (CDI) (NCT01222702) 〈http://clinicaltrials.gov/ct2/ show/NCT01222702〉 (accessed 4 April 2011).
173. Jia, L. et al. Pharmacodynamics and pharmacokinetics of SQ109, a new diamine-based antitubercular drug. Br. J. Pharmacol. 144, 80-87 (2005).
174. Protopopova, M. et al. Identification of a new antitubercular drug candidate, SQ109, from a combinatorial library of 1,2-ethylenediamines. J. Antimicrob. Chemother. 56, 968-974 (2005).
175. US National Institute of Health. Early Bactericidal Activity (EBA) of SQ109 in Adult Subjects with Pulmonary TB (SQ109EBA) (NCT01218217) 〈http://clinicaltrials.gov/ ct2/show/NCT01218217〉 (accessed 4 April 2011).
176. Matsumoto, M. et al. OPC-67683, a nitro-dihydro-imidazooxazole derivative
177. Sasaki, H. et al. Synthesis and antituberculosis activity of a novel series of optically active 6-nitro-2,3-dihydroimidazo[2,1-b]oxazoles. J. Med. Chem. 49, 7854-7860 (2006).
178. Singh, R. et al. PA-824 kills nonreplicating Mycobacterium tuberculosis by intracellular NO release. Science 322, 1392-1395 (2008).
179. Ginsberg, A. M., Laurenzi, M. W., Rouse, D. J., Whitney, K. D. & Spigelman, M. K. Safety, tolerability, and pharmacokinetics of PA-824 in healthy subjects. Antimicrob. Agents Chemother. 53, 3720-3725 (2009).
180. Denny, W. A. & Palmer, B. D. The nitroimidazooxazines (PA-824 and analogs): structure-activity relationship and mechanistic studies. Future Med. Chem. 2, 1295-1304 (2010).
181. Ahmad, Z. et al. PA-824 exhibits time-dependent activity in a murine model of tuberculosis. Antimicrob. Agents Chemother. 55, 239-245 (2011).
182. Goldstein, E. J. C. et al. In vitro activities of ABT-492, a new fluoroquinolone, against 155 aerobic and 171 anaerobic pathogens isolated from antral sinus puncture specimens from patients with sinusitis. Antimicrob. Agents Chemother. 47, 3008-3011 (2003).
183. Almer, L. S., Hoffrage, J. B., Keller, E. L., Flamm, R. K. & Shortridge, V. D. In vitro and bactericidal activities of ABT-492, a novel fluoroquinolone, against Gram-positive and Gram-negative organisms. Antimicrob. Agents Chemother. 48, 2771-2777 (2004).
184. Lemaire, S., Tulkens, P. M. & Van, B. F. Contrasting effects of acidic pH on the extracellular and intracellular activities of the anti-Gram-positive fluoroquinolones moxifloxacin and delafloxacin against Staphylococcus aureus. Antimicrob. Agents Chemother. 55, 649-658 (2011).
185. Emrich, N.- C., Heisig, A., Stubbings, W., Labischinski, H. & Heisig, P. Antibacterial activity of finafloxacin under different pH conditions against isogenic strains of Escherichia coli expressing combinations of defined mechanisms of fluoroquinolone resistance. J. Antimicrob. Chemother. 65, 2530-2533 (2010).
186. Higgins, P. G., Stubbings, W., Wisplinghoff, H. & Seifert, H. Activity of the investigational fluoroquinolone finafloxacin against ciprofloxacin-sensitive and -resistant Acinetobacter baumannii isolates. Antimicrob. Agents Chemother. 54, 1613-1615 (2010).
187. Morrow, B. J. et al. In vitro antibacterial activities of JNJ-Q2, a new broad-spectrum fluoroquinolone. Antimicrob. Agents Chemother. 54, 1955-1964 (2010).
188. US National Institutes of Health. Efficacy and Safety Study of JNJ-32729463 Compared with Moxifloxacin for the Treatment of Subjects Requiring Hospitalization for Community-Acquired Bacterial Pneumonia (NCT01198626) 〈http://clinicaltrials. gov/ct2/show/NCT01198626〉 (accessed 4 April 2011).
189. Jones, R. N., Biedenbach, D. J., Ambrose, P. G. & Wikler, M. A. Zabofloxacin (DW-224a) activity against Neisseria gonorrhoeae including quinolone-resistant strains. Diagn. Microbiol. Infect. Dis. 62, 110-112 (2008).
190. Park, H. S., Jung, S. J., Kwak, J.- H., Choi, D.- R. & Choi, E.- C. DNA gyrase and topoisomerase IV are dual targets of zabofloxacin in Streptococcus pneumoniae. Int. J. Antimicrob. Agents 36, 97-98 (2010).
191. Arjona, A. Nemonoxacin: quinolone antibiotic. Drugs Future 34, 196-203 (2009).
192. Chung, D. T. et al. Multiple-dose safety, tolerability, and pharmacokinetics of oral nemonoxacin (TG-873870) in healthy volunteers. Antimicrob. Agents Chemother. 54, 411-417 (2009).
193. Lin, L. et al. Dose escalation study of the safety, tolerability, and pharmacokinetics of nemonoxacin (TG-873870), a novel potent broad-spectrum nonfluorinated quinolone, in healthy volunteers. Antimicrob. Agents Chemother. 54, 405-410 (2009).
194. Lauderdale, T.- L., Shiau, Y.- R., Lai, J.- F., Chen, H.- C. & King, C.- H. R. Comparative in vitro activities of nemonoxacin (TG-873870), a novel nonfluorinated quinolone, and other quinolones against clinical isolates. Antimicrob. Agents Chemother. 54, 1338-1342 (2010).
195. Schneider, P., Hawser, S. & Islam, K. Iclaprim, a novel diaminopyrimidine with potent activity on trimethoprim sensitive and resistant bacteria. Bioorg. Med. Chem. Lett. 13, 4217-4221 (2003).
196. Hawser, S., Lociuro, S. & Islam, K. Dihydrofolate reductase inhibitors as antibacterial agents. Biochem. Pharmacol. 71, 941-948 (2006).
197. Krievins, D., Brandt, R., Hawser, S., Hadvary, P. & Islam, K. Multicenter, randomized study of the efficacy and safety of intravenous iclaprim in complicated skin and skin structure infections. Antimicrob. Agents Chemother. 53, 2834-2840 (2009).
198. Sincak, C. A. & Schmidt, J. M. Iclaprim, a novel diaminopyrimidine for the treatment of resistant Gram-positive infections. Ann. Pharmacother. 43, 1107-1114 (2009).
199. Skripkin, E. et al. Rw-01, a new family of oxazolidinones that overcome ribosome-based linezolid resistance. Antimicrob. Agents Chemother. 52, 3550-3557 (2008).
200. Zhou, J. et al. Design at the atomic level: design of biaryloxazolidinones as potent orally active antibiotics. Bioorg. Med. Chem. Lett. 18, 6175-6178 (2008).
201. Lemaire, S. et al. Cellular pharmacodynamics of the novel biaryloxazolidinone radezolid: studies with infected phagocytic and nonphagocytic cells, using Staphylococcus aureus, Staphylococcus epidermidis, Listeria monocytogenes, and Legionella pneumophila. Antimicrob. Agents Chemother. 54, 2549-2559 (2010).
202. Lemaire, S., Tulkens, P. M. & Van, B. F. Cellular pharmacokinetics of the novel biaryloxazolidinone radezolid in phagocytic cells: studies with macrophages and polymorphonuclear neutrophils. Antimicrob. Agents Chemother. 54, 2540-2548 (2010).
203. Page, M. G. P., Dantier, C. & Desarbre, E. In vitro properties of BAL30072, a novel siderophore sulfactam with activity against multiresistant Gram-negative bacilli. Antimicrob. Agents Chemother. 54, 2291-2302 (2010).
204. Mushtaq, S., Warner, M. & Livermore, D. Activity of the siderophore monobactam BAL30072 against multiresistant non-fermenters. J. Antimicrob. Chemother. 65, 266-270 (2010).
205. Basilea Pharmaceutica. Basilea Initiates Phase I Clinical Program of its Novel Antibiotic BAL3007 (press release 23 November 2010) 〈http://www. basilea.com/ News-and-Media/Basilea-initiates-phase-I-clinical-program-of-its- novel-antibiotic- BAL30072/381〉 (2010).
206. Biedenbach, D. J., Jones, R. N., Ivezic-Schoenfeld, Z., Paukner, S. & Novak, R. In vitro antibacterial spectrum of BC-7013, a novel pleuromutilin derivative for topical use in humans. 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (San Francisco, CA), Poster F1-1521 (2009).
207. Craig, W. A., Andes, D., Ivezic-Schoenfeld, Z., Wicha, W. W. & Novak, R. In vivo pharmacodynamic activity of BC-3205, a novel pleuromutilin derivative. 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (San Francisco, CA), Poster F1-1504 (2009).
208. US National Institutes of Health. A Study in Healthy Volunteers to Assess Safety and Blood Levels of AZD9742 after Multiple Doses Over 14 Days (NCT01064388) 〈http://clinicaltrials.gov/ct2/show/NCT01064388〉 (accessed 4 April 2011).
209. Koul, A., Arnoult, E., Lounis, N., Guillemont, J. & Andries, K. The challenge of new drug discovery for tuberculosis. Nature 469, 483-490 (2011).
210. Barbachyn, M. R. et al. Identification of a novel oxazolidinone (U-100480) with potent antimycobacterial activity. J. Med. Chem. 39, 680-685 (1996).
211. Wallis, R. S. et al. Pharmacokinetics and whole-blood bactericidal activity against Mycobacterium tuberculosis of single doses of PNU-100480 in healthy volunteers. J. Infect. Dis. 202, 745-751 (2010).
212. Williams, K. N. et al. Promising antituberculosis activity of the oxazolidinone PNU-100480 relative to that of linezolid in a murine model. Antimicrob. Agents Chemother. 53, 1314-1319 (2009).