Antibiotics and bacterial resistance in the 21st century

Perspectives in Medicinal Chemistry

Volumn , Issue 6, 2014, Pages 25-64

  Fair, Richard J ^a   Tor, Yitzhak ^b  

^a MAX PLANCK INSTITUTE OF COLLOIDS AND INTERFACES   (Germany)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Antibiotic resistance mechanisms; Antibiotics; Drug resistant bacteria; Novel antibiotic targets

Indexed keywords

AMIKACIN; AMINOGLYCOSIDE DERIVATIVE; ANTIBIOTIC AGENT; AZITHROMYCIN; CEPHALOSPORIN DERIVATIVE; CETHROMYCIN; CHLORAMPHENICOL; CLARITHROMYCIN; COTRIMOXAZOLE; DALBAVANCIN; DAPTOMYCIN; ERAVACYCLINE; ERYTHROMYCIN; MACROLIDE; MEROPENEM; OMADACYCLINE; ORITAVANCIN; PIPERACILLIN PLUS TAZOBACTAM; PLAZOMICIN; QUINOLINE DERIVED ANTIINFECTIVE AGENT; RIFAMYCIN DERIVATIVE; STREPTOGRAMIN DERIVATIVE; SULBACTAM; SULFONAMIDE; TELITHROMYCIN; TETRACYCLINE DERIVATIVE; TIGECYCLINE; TOBRAMYCIN; TRIMETHOPRIM; UNINDEXED DRUG;

ALLERGIC REACTION; ANTIBACTERIAL ACTIVITY; ANTIBIOTIC RESISTANCE; ARTICLE; BACTERIAL INFECTION; BLOOD DYSCRASIA; BLURRED VISION; CYSTIC FIBROSIS; DRUG CLASSIFICATION; DRUG COST; DRUG POTENTIATION; DRUG RESEARCH; DRUG STRUCTURE; ECONOMIC ASPECT; FOOD INDUSTRY; GRAM NEGATIVE BACTERIUM; GRAM POSITIVE BACTERIUM; HEALTH CARE COST; HISTORY; HOSPITAL INFECTION; HUMAN; LIVER FAILURE; LUNG INFECTION; MORBIDITY; MORTALITY; MULTIDRUG RESISTANT TUBERCULOSIS; NEPHROTOXICITY; NONHUMAN; OTOTOXICITY; PSEUDOMONAS INFECTION; STEVENS JOHNSON SYNDROME; STRUCTURE ANALYSIS; TRAVELLER DIARRHEA; TUBERCULOSIS; UNSPECIFIED SIDE EFFECT;

EID: 84926642568     PISSN: None     EISSN: 1177391X     Source Type: Journal    
DOI: 10.4137/PMC.S14459     Document Type: Article

References (427)

1. Appelbaum PC, 2012 and Beyond: Potential for the Start of a Second Pre-antibiotic Era? J Antimicrob Chemother. 2012;67(9):2062-8.
2. Center for Disease Control and Prevention. Achievements in Public Health, 1900-1999: Control of Infectious Diseases. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm4829a1.htm. Accessed December 20, 2013.
3. Center for Disease Control and Prevention. World Health Day: Media Fact Sheet. Available at: http://www.cdc.gov/media/releases/2011/f0407_antimicrobialresistance.pdf. Accessed December 20, 2013.
4. Center for Disease Control and Prevention. Antibiotic Resistance Threats in the United States, 2013. Available at: http://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf. Accessed March 19, 2014.
5. European Medicine Agency. The bacterial challenge: time to react. A call to narrow the gap between multidrug-resistant bacteria in the EU and the development of new antibacterial agents. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Report/2009/11/WC500008770.pdf. Accessed: December 20, 2013.
6. Sipahi OR, Effects of Antibiotic Resistance on Industrial Antibiotic R&D. Expert Rev Anti Infect Ther. 2008;6(4):523-39.
7. Shlaes DM. Antibiotics: The Perfect Storm. The Netherlands: Springer; 2010.
8. Spellberg B, Guidos R, Gilbert D, et al. The Epidemic of Antibiotic-resistant Infections: A Call to Action for the Medical Community from the Infectious Diseases Society of America. Clin Infect Dis 2008;46(2):155-64.
9. Projan SJ. Why is Big Pharma Getting out of Antibacterial Drug Discovery? Curr Opin Microbiol. 2003;6(5):427-30.
10. Power E. Impact of Antibiotic Restrictions: The Pharmaceutical Perspective. Clin Microb Infect. 2006;12(Suppl. 5):25-34.
11. Boucher HW, Talbot GH, Benjamin Jr DK, et al. 10 x '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(12):1685-94.
12. Jabes D. The antibiotic R&D Pipeline: An Update. Curr Opin in Microbiol. 2011;14(5):564-9.
13. Moellering RC. Discovering New Antimicrobial Agents. Int J Antimicrob Agents. 2011;37(1):2-9.
14. WHO: Department of Communicable Disease Surveillance and Response. WHO Global Strategy for Containment of Antimicrobial Resistance. Available at: http://www.who.int/csr/resources/publications/drugresist/en/EGlobal_Strat.pdf. Accessed: December 20, 2013.
15. European Centre for Disease Prevention and Control. Communication from the Commission to the European Parliament and the Council. Action plan against the rising threats from Antimicrobial Resistance. Available at: http://ec.europa.eu/dgs/health_consumer/docs/communication_amr_2011_748_en.pdf. Accessed: December 20, 2013.
16. Nathan C. Antibiotics at the Crossroads. Nature. 2004;431(7011):899-902.
17. Spellberg B, Blaser M, Guidos RJ, Boucher HW, Bradley JS. Combating Antimicrobial Resistance: Policy Recommendations to Save Lives. Clin Infect Dis. 2011;52(Suppl. 5):S397-428.
18. The Wall Street Journal. FDA Chief Focuses on Antibiotic Resistance. Available at: http://online.wsj.com/article/SB10001424052748703735804575536411612671060.html. Accessed December 20, 2013.
19. Brookings Institution. Facilitating Antibacterial Drug Development 2012. Available at: http://www.brookings.edu/events/2012/05/09-antibacterialdrug-development. Accessed December 20, 2013.
20. Carling P, Fung T, Killion A, Terrin N, Barza M. Favorable Impact of a Multidisciplinary Antibiotic Management Program Conducted During 7 Years. Infect Control Hosp Epidemiol. 2003;24(9):699-706.
21. Yong MK, Buising KL, Cheng AC, Thursky KA. Improved Susceptibility of Gram-negative Bacteria in an Intensive Care Unit Following Implementation of a Computerized Antibiotic Decision Support System. J Antimicrob Chemother. 2010;65(5):1062-9.
22. Fishman N. Antimicrobial Stewardship. Am J Med. 2006;119(6 Suppl. 1):S53-61.
23. Pendleton JN, Gorman SP, Gilmore BF. Clinical Relevance of the ESKAPE Pathogens. Expert Rev Anti Infect Ther. 2013;11(3):297-308.
24. Jacob JT, Gaynes RP. Emerging Trends in Antibiotic use in US Hospitals: Quality, Quantification and Stewardship. Expert Rev Anti Infect Ther. 2010;8(8):893-902.
25. Palumbi SR. Science, Humans as the World's Greatest Evolutionary Force. 2001;293(5536):1786-90.
26. Rice LB. The Maxwell Finland Lecture: For the Duration-rational Antibiotic Administration in an Era of Antimicrobial Resistance and Clostridium difficile. Clin Infect Dis 2008;46(4):491-6.
27. Seppala H, Klaukka T, Lehtonen R, Nenonen E, Huovinen P. Outpatient use of Erythromycin: Link to Increased Erythromycin Resistance in Group A Streptococci. Clin Infect Dis. 1995;21(6):1378-85.
28. Goossens H, Ferech M, Vander SR, Elseviers M. Outpatient Antibiotic use in Europe and Association with Resistance: A Cross-national Database Study. Lancet. 2005;365(9459):579-87.
29. Seppälä H, Klaukka T, Vuopio-Varkila J, Muotiala A, Helenius H, Lager K. The Effect of Changes in the Consumption of Macrolide Antibiotics on Erythromycin Resistance in Group A Streptococci in Finland. Finnish Study Group for Antimicrobial Resistance. N Engl J Med. 1997;337(7):441-6.
30. Anonymous, Recent trends in Antimicrobial Resistance among Streptococcus pneumoniae and Staphylococcus aureus Isolates: The French Experience. Euro Surveill. 2008;13(46):19035.
31. Special Eurobarometer 338 'Antimicrobial Resistance', 2009. Survey Commissioned by the Directorate-General for Health and Consumers and Coordinated by the Directorate-General Communication ('Research and Political Analysis' Unit). Available at: http://ec.europa.eu/public opinion/index fr.htm.Accessed December 20, 2013.
32. Kunin CM. Resistance to Antimicrobial Drugs: A Worldwide Calamity. Ann Intern Med. 1993;118(7):557-61.
33. Gorbach SL. Antimicrobial use in Animal Feed: Time to Stop. N Engl J Med. 2001;345(16):1202-3.
34. Official Journal of the European Union. Regulation (EC) No. 1831/2003 of the European Parliament and of The Council of 22 September 2003 on Additives for use in Animal Nutrition. Available at: http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri =OJ:L:2003:268:0029:0043:EN:PDF. Accessed: December 20, 2013.
35. FDA News Release. FDA Takes Steps to Protect Public Health. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm299802.htm. Accessed: December 20, 2013.
36. Qin X, Razia Y, Johnson JR, et al. Ciprofloxacin-resistant Gram-negative Bacilli in the Fecal Microflora of Children. Antimicrob Agents Chemother. 2006;50(10):3325-9.
37. van den Bogaard AE, London N, Driessen C, Stobberingh EE. Antibiotic Resistance of Faecal Escherichia coli in Poultry, Poultry Farmers and Poultry Slaughterers. J Antimicrob Chemother. 2001;47(6):763-71.
38. Mead PS, Slutsker L, Dietz V, McCaig LF, Bresee JS, Shapiro C. Food-related Illness and Death in the United States. Emerg Infect Dis. 1999;5(5):607-25.
39. Wegener HC, Aarestrup FC, Jensen LB, Hammerum AM, Bager F. Use of Antimicrobial Growth Promoters in Food Animals and Enterococcus faecium Resistance to Therapeutic Antimicrobial Drugs in Europe. Emerg Infect Dis. 1999;5(3):329-35.
40. Wegener HC. Antibiotics in Animal Feed and their Role in Resistance Development. Curr Opin Microbiol. 2003;6(5):439-45.
41. European Medicines Agency. Trends in the Sales of Veterinary Antimicrobial Agents in Nine European Countries. Reporting period: 2005-2009. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/Report/2011/09/WC500112309.pdf. Accessed: December 20, 2013.
42. Walsh C. Antibiotics: Actions, Origins, Resistance. American Society for Microbiology (ASM) Press: Washington, DC, 2003.
43. Wright GD, Poinar H. Antibiotic Resistance is Ancient: Implications for Drug Discovery. Trends in Microbiol. 2012;20(4):157-9.
44. Davies J, Davies D. Origins and Evolution of Antibiotic Resistance. Microbiol Mol Biol Rev. 2010;74(3):417-33.
45. Lyon BR, Skurray R. Antimicrobial Resistance of Staphylococcus aureus: Genetic Basis. Microbiol Rev. 1987;51(1):88-134.
46. Schaack S, Gilbert C, Feschotte C. Promiscuous DNA: Horizontal Transfer of Transposable Elements and why it Matters for Eukaryotic Evolution. Trends Ecol Evol. 2010;25(9):537-46.
47. Hall BG, Barlow M. Structure-based Phylogenies of the Serine Beta-lactamases. J Mol Evol. 2003;57(3):255-60.
48. D'Costa VM, King CE, Kalan L, et al. Antibiotic Resistance is Ancient. Nature. 2011;477(7365):457-61.
49. Baltz RH. Antibiotic Discovery from Actinomycetes: Will a Renaissance Follow the Decline and Fall? SIM News. 2005;55:186-96.
50. D'Costa VM, McGrann KM, Hughes DW, Wright GD. Sampling the Antibiotic Resistome. Science. 2006;311(5759):374-7.
51. Pallecchi L, Bartoloni A, Paradisi F, Rossolini GM. Antibiotic Resistance in the Absence of Antimicrobial Use: Mechanisms and Implications. Expert Rev Anti Infect Ther. 2008;6(5):725-32.
52. Kluytmans J, van Belkum A, Verbrugh H. Nasal Carriage of Staphylococcus aureus: Epidemiology, Underlying Mechanisms, and Associated Risks. Clin Microbiol Rev. 1997;10(3):505-20.
53. Boubaker K, Diebold P, Blanc DS, et al. Panton-Valentine Leukocidin and Staphyloccoccal Skin Infections in Schoolchildren. Emerging Infect Dis. 2004;10(1):121-4.
54. Parsonnet J, Hansmann MA, Delaney ML, et al. Prevalence of Toxic Shock Syndrome Toxin 1-Producing Staphylococcus aureus and the Presence of Antibodies to this Superantigen in Menstruating Women. J. Clin. Microbiol. 2005;43(9):4628-34.
55. Lina G, Piémont Y, Godail-Gamot F, et al. Involvement of Panton-Valentine Leukocidin-producing Staphylococcus aureus in Primary Skin Infections and Pneumonia. Clin Infect Dis. 1999;29(5):1128-32.
56. Vandenesch F, Naimi T, Enright MC, et al. Community-acquired Methicillin-resistant Staphylococcus aureus Carrying Panton-Valentine Leukocidin Genes: Worldwide Emergence. Emerging Infect Dis. 2003;9(8):978-84.
57. Gillet Y, Issartel B, Vanhems P, et al. Association Between Staphylococcus aureus Strains Carrying Gene for Panton-Valentine Leukocidin and Highly Lethal Necrotising Pneumonia in Young Immunocompetent Patients. Lancet. 2002;359(9308):753-9.
58. Boucher HW, Talbot GH, Bradley JS, et al. Bad Bugs, No Drugs: No ESKAPE! An Update from the Infectious Diseases Society of America. Clin Infect Dis. 2009;48(1):1-2.
59. Liu GY, Essex A, Buchanan JT, et al. Staphylococcus aureus Golden Pigment Impairs Neutrophil Killing and Promotes Virulence Through its Antioxidant Activity. J Exp Med. 2005;202(2):209-15.
60. Clauditz A, Resch A, Wieland KP, Peschel A, Götz F. Staphyloxanthin Plays a Role in the Fitness of Staphylococcus aureus and its Ability to Cope with Oxidative Stress. Infect Immun. 2006;74(8):4950-3.
61. Costerton JW, Stewart PS, Greenberg EP. Bacterial Biofilms: A Common Cause of Persistent Infections. Science. 1999;284(5418):1318-22.
62. Fischbach MA, Walsh CT. Antibiotics for Emerging Pathogens. Science. 2009;325(5944):1089-93.
63. Klevens RM, Morrison MA, Nadle J, et al. Invasive Methicillin-resistant Staphylococcus aureus Infections in the United States. JAMA. 2007;298(15):1763-71.
64. Talbot GH, Bradley J, Edwards Jr JE, 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. Clin Infect Dis. 2006;42(5):657-68.
65. Smith A. Bacterial resistance to antibiotics. In: Hugo and Russell's Pharmaceutical Microbiology. Denyer SP, Hodges NA, Gorman SP (Eds). Blackwell Science Ltd, Oxford, UK, 2007.
66. Appelbaum PC. Reduced Glycopeptide Susceptibility in Methicillin-resistant Staphylococcus aureus (MRSA). Int J Antimicrob Agents. 2007;30(5):398-408.
67. Chang S, Sievert DM, Hageman JC, et al. Infection with Vancomycin-resistant Staphylococcus aureus Containing the vanA Resistance Gene. N Engl J Med. 2003;348(14):1342-47.
68. Department of Health, Standing Medical Advisory Committee, Sub-Group on Antimicrobial Resistance. The Path of Least Resistance. Available at: http://antibiotic-action.com/wp-content/uploads/2011/07/Standing-Medical-Advisory-Committee-The-path-of-least-resistance-1998.pdf. Accessed: December 20, 2013.
69. Fisher K, Phillips C. The Ecology, Epidemiology and Virulence of Enterococcus. Microbiology. 2009;155(6):1749-57.
70. Livermore DM. Future Directions with Daptomycin. J Antimicrob Chemother. 2008;62 Suppl(3):iii41-9.
71. Arias CA, Contreras GA, Murray BE. Management of Multidrug-resistant Enterococcal Infections. CMI. 2010;16(6):555-62.
72. van Wamel WJ, Hendrick AP, Bonten MJ, Top J, Posthuma G, Willems RJ. Growth Condition-dependent Esp Expression by Enterococcus faecium Affects Initial Adherence and Biofilm Formation. Infect Immun. 2007;75(2):924-31.
73. Zinner SH. The Search for New Antimicrobials: Why we Need New Options. Expert Rev Anti Infect Ther. 2005;3(6):907-13.
74. Regev-Yochay G, Trzcinski K, Thompson CM, Malley R, Lipsitch M. Interference Between Streptococcus pneumoniae and Staphylococcus aureus: In vitro Hydrogen Peroxide-mediated Killing by Streptococcus pneumoniae. J Bacteriol. 2006;188(13):4996-5001.
75. Jacobs MR. Streptococcus pneumoniae: Epidemiology and Patterns of Resistance. Am J Med. 2004;117 Suppl(3A):S3-15.
76. Karchmer AW. Increased Antibiotic Resistance in Respiratory Tract Pathogens: PROTEKT US--An Update. Clin Infect Dis. 2004;39 Suppl(3):S142-50.
77. Edelstein PH. Pneumococcal Resistance to Macrolides, Lincosamides, Ketolides, and Streptogramin B Agents: Molecular Mechanisms and Resistance Phenotypes. Clin Infect Dis. 2004;38 Suppl(4):S322-7.
78. von Gottberg A, Klugman KP, Cohen C, et al Emergence of Levofloxacin-non-susceptible Streptococcus pneumoniae and Treatment for Multidrug-resistant Tuberculosis in Children in South Africa: A Cohort Observational Surveillance Study. Lancet. 2008;371(9618):1108-13.
79. Barth H, Aktories K, Popoff MR, Stiles BG. Binary Bacterial Toxins: Biochemistry, Biology, and Applications of Common Clostridium and Bacillus Proteins. Microbiol Mol Biol Rev. 2004;68(3):373-402.
80. Clabots CR, Johnson S, Olson MM, Peterson LR, Gerding DN. Acquisition of Clostridium difficile by Hospitalized Patients: Evidence for Colonized New Admissions as a Source of Infection. J Infect Dis. 1992;166(3):561-7.
81. Planche T, Aghaizu A, Holliman R, Riley P, Poloniecki J, Breathnach A, Krishna S. Diagnosis of Clostridium difficile Infection by Toxin Detection Kits: A Systematic Review. Lancet Infect Dis. 2008;8(12):777-84.
82. Pepin J, Saheb N, Coulombe MA, et al. Emergence of Fluoroquinolones as the Predominant Risk Factor for Clostridium difficile-Associated Diarrhea: A Cohort Study During an Epidemic in Quebec. Clin Infect Dis. 2005;41(9):1254-60.
83. McDonald LC, Killgore GE, Thompson A, et al. An Epidemic, Toxin Gene-variant Strain of Clostridium difficile. N Engl J Med. 2005;353(23):2433-41.
84. Loffler CA, MacDougall C. Update on Prevalence and Treatment of Methicillin-resistant Staphylococcus aureus Infections. Exp Rev Anti Infect Ther. 2007;5(6):961-81.
85. Daxboeck F, Budic T, Assadian O, Reich M, Koller W. Economic Burden Associated with Multi-resistant Gram-negative Organisms Compared with that for Methicillin-resistant Staphylococcus aureus in a University Teaching Hospital. J Hosp Infect. 2006;62(2):214-8.
86. Arias CA, Murray BE, Antibiotic-resistant Bugs in the 21st Century--A Clinical Super-challenge. N Engl J Med. 2009;360(5):439-43.
87. Kumarasamy KK, Toleman MA, Walsh TM, et al. Emergence of a New Antibiotic Resistance Mechanism in India, Pakistan, and the UK: A Molecular, Biological, and Epidemiological Study. Lancet Infect Dis. 2010;10(9): 597-602.
88. Flynn JL, Chan J. Immune Evasion by Mycobacterium tuberculosis: Living with the Enemy. Curr Opin Immunol. 2003;15(4):450-5.
89. Niederweis M, Danilchanka O, Huff J, Hoffmann C, Engelhardt H. Mycobacterial Outer Membranes: In Search of Proteins. Trends in Microbiol. 2010;18(3):109-16.
90. World Health Organization. Tuberculosis Fact Sheet. Available at: http://www.who.int/mediacentre/factsheets/fs104/en/index.html. Accessed: December 20, 2013.
91. Anonymous. Extensively Drug-resistant Tuberculosis (XDR-TB): Recommendations for Prevention and Control. Wkly Epidemiol Rec. 2006;81(45):430-2.
92. Dorman SE, Chaisson RE. From Magic Bullets Back to the Magic Mountain: The Rise of Extensively Drug-resistant Tuberculosis. Nat Med. 2007;13(3):295-8.
93. Kim DH, Hee J, Park SK, et al. Treatment Outcomes and Long-term Survival in Patients with Extensively Drug-resistant Tuberculosis. Am J Respir Crit Care Med. 2008;178(10):1075-82.
94. Kaper JB, Nataro JP, Mobley HL. Pathogenic Escherichia coli. Nat Rev Microbiol. 2004;2(2):123-40.
95. O'Brien AD, Newland JW, Miller SF, Holmes RK, Smith HW, Formal SB. Shiga-like Toxin-converting Phages from Escherichia coli Strains that Cause Hemorrhagic Colitis or Infantile Diarrhea. Science. 1984;226(4675): 694-6.
96. Livermore DM, Hope R, Brick G, Lillie M, Reynolds R. Non-susceptibility Trends among Enterobacteriaceae from Bacteraemias in the UK and Ireland, 2001-06. J Antimicrob Chemother. 2008;62(Suppl 2):ii41-54.
97. Poirel L, Lagrutta E, Taylor P, Pham J, Nordmann P. Emergence of Metallo-β-lactamase NDM-1 Producing Multidrug-resistant Escherichia coli in Australia. Antimicrob Agents Chemother. 2010;54(11):4914-6.
98. Solé M, Pitart C, Roca I, et al. First Description of an Escherichia coli Strain Producing NDM-1 Carbapenemase in Spain. Antimicrob Agents Chemother. 2011;55(9):4402-04.
99. Pfeifer Y, Witte W, Holfelder M, Busch J, Nordmann P, Poirel L. NDM-1 Producing Escherichia coli in Germany. Antimicrob Agents Chemother. 2011;55(3):1318-9.
100. Nordmann P, Poirel L, Toleman MA, Walsh TA. Does Broad-spectrum Beta-lactam Resistance due to NDM-1 Herald the End of the Antibiotic Era for Treatment of Infections Caused by Gram-negative Bacteria? J Antimicrob Chemother. 2011;66(4):689-92.
101. Souli M, Galani I, Giamarellou H. Emergence of Extensively Drug-resistant and Pandrug-resistant Gram-negative Bacilli in Europe. Euro Surveill. 2008;13(47):pii:19045.
102. Rodloff AC, Leclercq R, Debbia EA, Canton R, Oppenheim BA, Dowzicky MJ. Comparative Analysis of Antimicrobial Susceptibility among Organisms from France, Germany, Italy, Spain and the UK as Part of the Tigecycline Evaluation and Surveillance Trial. Clin Microbiol Infect. 2008;14(4):307-14.
103. Kobayashi S, Kuzuyama T, Seto H. Characterization of the fomA and fomB Gene Products from Streptomyces wedmorensis, which Confer Fosfomycin Resistance on Escherichia coli. Antimicrob Agents Chemother. 2000;44(3):647-650.
104. New York State Department of Health. Health Commissioner Releases E. coli Outbreak Report. Available at: http://www.health.ny.gov/press/releases/2000/ecoli.htm. Accessed December 20, 2013.
105. Frank C, Werber D, Cramer JP, et al. Epidemic Profile of Shiga-toxin Producing Escherichia coli O104:H4 Outbreak in Germany. N Engl J Med. 2011;365(19):1771-80.
106. Hart CA, Winstanley C. Persistent and Aggressive Bacteria in the Lungs of Cystic Fibrosis Children. Br Med Bull. 2002;61:81-96.
107. Oliver A, Canton R, Campo P, Baquero F, Blazquez J. High Frequency of Hypermutable Pseudomonas aeruginosa in Cystic Fibrosis Lung Infection. Science. 2000;288(5469):1251-4.
108. Henrichfreise B, Wiegand I, Pfister W, Wiedemann B. Resistance Mechanisms of Multiresistant Pseudomonas aeruginosa Strains from Germany and Correlation with Hypermutation. Antimicrob Agents Chemother. 2007;51(11):4062-70.
109. Lee VT, Smith RS, Tummler B, Lory S. Activities of Pseudomonas aeruginosa Effectors Secreted by the Type III Secretion System in vitro and During Infection. Infect Immun. 2005;73(3):1695-705.
110. Adair FW, Geftic SG, Gelzer J. Resistance of Pseudomonas to Quaternary Ammonium Compounds. I. Growth in Benzalkonium Chloride Solution. Appl Microbiol. 1969;18(3):299-302.
111. Nikaido H. Molecular Basis of Bacterial Outer Membrane Permeability Revisited. Microbiol Mol Biol Rev. 2003;67(4):593-656.
112. Fothergill JL, Winstanley C, James CE. Novel Therapeutic Strategies to Counter Pseudomonas aeruginosa Infections. Expert Rev Anti Infect Ther. 2012;10(2):219-35.
113. Bush K. Alarming β-lactamase-mediated Resistance in Multidrug-resistant Enterobacteriaceae. Curr Opin Microbiol. 2010;13(5):558-64.
114. Livermore DM. Multiple Mechanisms of Antimicrobial Resistance in Pseudomonas aeruginosa: Our Worst Nightmare? Clin Infect Dis. 2002;34(5):634-40.
115. Morero NR, Monti MR, Argaraña CE. Effect of Ciprofloxacin Concentration on the Frequency and Nature of Resistant Mutants Selected from Pseudomonas aeruginosa mutS and mutT Hypermutators. Antimicrob Agents Chemother. 2011;55(8):3668-76.
116. Deplano A, Denis O, Poirel L, et al. Struelens MJ, Molecular Characterization of an Epidemic Clone of Panantibiotic-resistant Pseudomonas aeruginosa. J Clin Microbiol. 2005;43(3):1198-204.
117. Lolans K, Queenan AM, Bush K, Sahud A, Quinn JP. First Nosocomial Outbreak of Pseudomonas aeruginosa Producing an Integron-borne Metallo-beta-lactamase (VIM-2) in the United States. Antimicrob Agents Chemother. 2005;49(8):3538-40.
118. Crespo MP, Woodford N, Sinclair A, et al. Outbreak of Carbapenem-resistant Pseudomonas aeruginosa Producing VIM-8, a Novel Metallo-beta-lactamase, in a Tertiary Care Center in Cali, Colombia. J Clin Microbiol. 2004;42(11):5094-101.
119. Kallen AJ, Srinivasan A. Current Epidemiology of Multidrug-resistant Gram-negative Bacilli in the United States. Infect Control Hosp Epidemiol. 2010;31 Suppl(1):S51-4.
120. Abbo A, Carmeli Y, Navon-Venezia S, Siegman-Igra Y, Schwaber MJ. Impact of Multi-drug-resistant Acinetobacter baumannii on Clinical Outcomes. Eur J Clin Microbiol Infect Dis. 2007;26(11):793-800.
121. Vila J, Martí S, Sánchez-Céspedes J. Porins, Efflux Pumps and Multidrug Resistance in Acinetobacter baumannii. J. Antimicrob. Chemother. 2007;59(6):1210-5.
122. Kramer A, Schwebke I, Kampf G. How Long do Nosocomial Pathogens Persist on Inanimate Surfaces? A Systematic Review. BMC Infect. Dis. 2006;6:130.
123. Houang ET, Sormunen RT, Lai L, Chan CY, Leong AS. Effect of Desiccation on the Ultrastructural Appearances of Acinetobacter baumannii and Acinetobacter lwoffii. J Clin Pathol. 1998;51(10):786-8.
124. Gootz TD, Marra A. Acinetobacter baumannii: An Emerging Multidrug-resistant Threat. Expert Rev Anti Infect Ther. 2008;6(3):309-25.
125. Joly-Guillou ML. Clinical Impact and Pathogenicity of Acinetobacter. Clin Microbiol Infect. 2005;11(11):868-73.
126. Choi CH, Lee EY, Lee Park YC, et al. Outer Membrane Protein 38 of Acinetobacter baumannii Localizes to the Mitochondria and Induces Apoptosis of Epithelial Cells. Cell Microbiol. 2005;7(8):1127-38.
127. Queenan AM, Bush K. Carbapenemases: The Versatile Beta-lactamases. Clin Microbiol Rev. 2007;20(3):440-58.
128. Sievert DM, Ricks P, Edwards JR, et al. Antimicrobial-resistant Pathogens Associated with Healthcare-associated Infections: Summary of Data Reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2009-2010. Infect Control Hosp Epidemiol. 2013;34(1):1-4.
129. Munoz-Price LS. Weinstein RA, Acinetobacter Infection. N Engl J Med. 2008;358(12):1271-81.
130. Macrae MB, Shannon KP, Rayner DM, Kaiser AM, Hoffman PN, French GL. A Simultaneous Outbreak on a Neonatal Unit of Two Strains of Multiply Antibiotic Resistant Klebsiella pneumoniae Controllable only by Ward Closure. J Hosp Infect. 2001;49(3):183-92.
131. Fontana C, Favaro M, Minelli S, et al. Acinetobacter baumannii in Intensive Care Unit: A Novel System to Study Clonal Relationship among the Isolates. BMC Infect Dis. 2008;8(8):79.
132. Podschun R, Ullmann U. Klebsiella spp. as Nosocomial Pathogens: Epidemiology, Taxonomy, Typing Methods, and Pathogenicity Factors. Clin Microbiol Rev. 1998;11(4):589-603.
133. Martinez-Martinez L, Pascual A, Jacoby GA. Quinolone Resistance from a Transferable Plasmid. Lancet. 1998;351(9105):797-9.
134. Yong D, Toleman MA, Giske CG, et al. Characterization of a New Metallo-beta-lactamase Gene, bla(NDM-1), and a Novel Erythromycin Esterase Gene Carried on a Unique Genetic Structure in Klebsiella pneumoniae Sequence Type 14 from India. Antimicrob Agents Chemother. 2009;53(12):5046-54.
135. Hawser SP, Bouchillon SK, Hoban DJ, Badal BD, Hsueh PR, Paterson DL. Emergence of High Levels of Extended-spectrum Beta-lactamase-producing Gram-negative Bacilli in the Asia-Pacific Region: Data from the Study for Monitoring Antimicrobial Resistance Trends (SMART) Program, 2007. Antimicrob Agents Chemother. 2009;53(8):3280-4.
136. Elemam A, Rahimian J, Mandell W. Infection with Panresistant Klebsiella pneumoniae: A Report of 2 Cases and a Brief Review of the Literature. Clin Infect Dis. 2009;49(2):271-4.
137. Castanheira M, Deshpande LM, Mathai D, Bell JM, Jones RN, Mendes RE. Early Dissemination of NDM-1-and OXA-181-producing Enterobacteriaceae in Indian Hospitals: Report from the SENTRY Antimicrobial Surveillance Program, 2006-2007. Antimicrob Agents Chemother. 2011;55(3):1274-8.
138. Park CH, Robicsek A, Jacoby GA, Sahm D, Hooper DC. Prevalence in the United States of aac(6')-Ib-cr Encoding a Ciprofloxacin-modifying Enzyme. Antimicrob Agents Chemother. 2006;50(11):3953-5.
139. Stern A, Brown M, Nickel P, Meyer TF. Opacity Genes in Neisseria gonorrhoeae: Control of Phase and Antigenic Variation. Cell. 1986;47(1):61-71.
140. Yokoi S, Deguchi T, Ozawa T, et al. Threat to Cefixime Treatment for Gonorrhea. Emerg Infect Dis. 2007;13(8):1275-7.
141. Palmer HM, Young H, Winter A, Dave J. Emergence and Spread of Azithromycin-resistant Neisseria gonorrhoeae in Scotland. J Antimicrob Chemother. 2008;62(3):490-4.
142. Livermore DM, Has the Era of Untreatable Infections Arrived? J Antimicrob Chemother. 2009;64 Suppl(1):i29-36.
143. Centers for Disease Control and Prevention. Healthcare-associated Infections (HAIs) - The Burden. Available at: http://www.cdc.gov/HAI/burden.html. Accessed December 20, 2013.
144. Allegranzi B, Bagheri Nejad S, Combescure C, et al. Burden of Endemic Health-care-associated Infection in Developing Countries: Systematic Review and Meta-analysis. Lancet. 2011;377(9761):228-41.
145. Paphitou NI. Antimicrobial Resistance: Action to Combat the Rising Microbial Challenges. Int J Antimicrob. Agents 2013;42S:S25-8.
146. Rice LB. Federal Funding for the Study of Antimicrobial Resistance in Nosocomial Pathogens: No ESKAPE. J Infect Dis. 2008;197(8):1079-81.
147. Silver LL, Challenges of Antibacterial Discovery. Clin Microbiol Rev. 2011;24(1):71-109.
148. Andes D, Anon J, Jacobs MR, Craig WA, Application of Pharmacokinetics and Pharmacodynamics to Antimicrobial Therapy of Respiratory Tract Infections. Clin Lab Med. 2004;24(2):477-502.
149. Newman DJ, Cragg GM, Natural Products as Sources of New Drugs over the Last 25 Years. J Nat Prod. 2007;70(3):461-77.
150. Singh SB, Barrett JF. Empirical Antibacterial Drug Discovery-Foundation in Natural Products. Biochem Pharmacol. 2006;71(7):1006-15.
151. Hansen JL, Moore PB, Steitz TA. Structures of Five Antibiotics Bound at the Peptidyl Transferase Center of the Large Ribosomal Subunit. J Mol Biol. 2003;330(5):1061-75.
152. Moore PB, Steitz TA. The Ribosome Revealed. Trends Biochem Sci. 2005;30(6):281-3.
153. Akerley BJ, Rubin EJ, Novick VL, Amaya K, Judson N, Mekalanos JJ. A Genome-scale Analysis for Identification of Genes Required for Growth or Survival of Haemophilus influenzae. Proc Natl Acad Sci USA. 2002;99(2):966-71.
154. Hutchison CA, Peterson SN, Gill SR, et al. Global Transposon Mutagenesis and a Minimal Mycoplasma Genome. Science. 1999;286(5447):2165-9.
155. Ji Y, Zhang B, Van SF, et al. Identification of Critical Staphylococcal Genes using Conditional Phenotypes Generated by Antisense RNA. Science. 2001; 293(5538):2266-9.
156. Kobayashi K, Ehrlich SD, Albertini A, et al. Essential Bacillus subtilis Genes. Proc Natl Acad Sci U S A. 2003;100(8):4678-83.
157. Forsyth RA, Haselbeck RJ, Ohlsen KL, et al. A Genome-wide Strategy for the Identification of Essential Genes in Staphylococcus aureus. Mol Microbiol. 2002;43(6):1387-400.
158. Infectious Diseases Society of America. The 10 x '20 Initiative: Pursuing a Global Commitment to Develop 10 New Antibacterial Drugs by 2020. Clin Infect Dis. 2010;50(8):1081-3.
159. Witting K, Smith RD. Discovery of Antibacterials and Other Bioactive Compounds from Microorganisms-evaluating Methodologies for Discovery and Generation of Non-ribosomal Peptide Antibiotics. Curr Drug Targets. 2011;12(11):1547-59.
160. Clardy J, Fischbach MA, Walsh CT. New Antibiotics from Bacterial Natural Products. Nat Biotechnol. 2006;24(12):1541-50.
161. Lomovskaya O, Lewis K. Emr, an Escherichia coli Locus for Multidrug Resistance. Proc Natl Acad Sci USA 1992;89(18):8938-42.
162. Li XZ, Nikaido H. Efflux-mediated Drug Resistance in Bacteria. Drugs. 2004;64(2):159-204.
163. Lewis K. Platforms for Antibiotic Discovery. Nat Rev Drug Disc. 2013;12(5): 371-87.
164. O'Shea R, Moser HE. Physicochemical Properties of Antibacterial Compounds: Implications for Drug Discovery. J Med Chem. 2008;51(10):2871-8.
165. Silver LL. Are Natural Products Still the Best Source for Antibacterial Discovery? The bacterial entry factor. Expert Opin Drug Discov. 2008;3(5): 487-500.
166. Hsieh PC, Siegel SA, Rogers B, Davis D, Lewis K. Bacteria Lacking a Multidrug Pump: A Sensitive Tool for Drug Discovery. Proc Natl Acad Sci USA 1998;95(12):6602-6.
167. Stermitz FR, Lorenz P, Tawara JN, Zenewicz LA, Lewis K. Synergy in a Medicinal Plant: Antimicrobial Action of Berberine Potentiated by 5'-Methoxyhydnocarpin, a Multidrug Pump Inhibitor. Proc. Natl Acad. Sci. USA 2000;97(4):1433-7.
168. Lewis K, Ausubel FM. Prospects for Plant-derived Antibacterials. Nature Biotech. 2006;24(12):1504-7.
169. Rock FL, Mao W, Yaremchuk A, et al. An Antifungal Agent Inhibits an Aminoacyl-tRNA Synthetase by Trapping tRNA in the Editing Site. Science. 2007;316(5832):1759-61.
170. Payne DJ, Gwynn MN, Holmes DJ, Pompliano DL. Drugs for Bad Bugs: Confronting the Challenges of Antibacterial Discovery. Nature Rev Drug Discov. 2007;6(1):29-40.
171. Singh SB, Young K, Miesel L. Screening Strategies for Discovery of Antibacterial Natural Products. Expert Rev Anti Infect Ther. 2011;9(8):589-613.
172. Boguski MS, Mandl KD, Sukhatme VP. Drug Discovery. Repurposing with a Difference. Science. 2009;324(5933):1394-5.
173. Andries K, Verhasselt P, Guillemont J, et al. A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis. Science. 2005;307(5707):223-7.
174. Moy TI, Ball AR, Anklesaria Z, Casadei G, Lewis K, Ausubel FM. Identification of Novel Antimicrobials using a Live-animal Infection Model. Proc Natl Acad Sci USA 2006;103(27):10414-9.
175. O'Rourke EJ, Conery AL, Moy TI. Whole-animal High-throughput Screens: The C. elegans Model. Methods Mol Biol. 2009;486l:57-75.
176. Galloway WRJD, Bender A, Welch M, Spring DR. The Discovery of Antibacterial Agents using Diversity-oriented Synthesis. Chem Commun. 2009;18: 2446-62.
177. Robinson A, Thomas GL, Spandl RJ, Welch M, Spring DR. Gemmacin B: Bringing Diversity Back into Focus. Org Biomol Chem. 2008;6(16):2978-81.
178. Wyatt EE, Galloway WRJD, Thomas GL, et al. Identification of an Anti-MRSA Dihydrofolate Reductase Inhibitor from a Diversity-oriented Synthesis. Chem Commun. 2008;40:4962-4.
179. Watve MG, Tickoo R, Jog MM, Bhole BD. How Many Antibiotics are Produced by the Genus Streptomyces? Arch Microbiol. 2001;176(5):386-90.
180. Weber T, Welzel K, Pelzer S, Vente A, Wohlleben W. Exploiting the Genetic Potential of Polyketide Producing Streptomycetes. J Biotechnol. 2003;106(2-3):221-32.
181. Baltz RH. Genetic Manipulation of Antibiotic-producing Streptomyces. Trends Microbiol. 1998;6(2):76-83.
182. Fischbach MA. Antibiotics from Microbes: Converging to Kill. Curr Opin Microbiol. 2009;12(5):520-7.
183. Bister B, Bischoff D, Ströbele M, et al. Angew Chem Int Ed. 2004;43(19):2574-6.
184. Laport MS, Santos OC, Muricy G. Marine Sponges: Potential Sources of New Antimicrobial Drugs. Curr Pharm Biotechnol. 2009;10(1):86-105.
185. Burgess JG, Jordan EM, Bregu M, Mearns-Spragg A, Boyd KG. Microbial Antagonism: A Neglected Avenue of Natural Products Research. J. Biotechnol. 1999;70(1-3):27-32.
186. Donia MS, Ravel J, Schmidt EW. A Global Assembly Line for Cyanobactins. Nat Chem Biol. 2008;4(6):341-3.
187. Partida-Martinez LP, Hertweck C. Pathogenic Fungus Harbours Endosymbiotic Bacteria for Toxin Production. Nature. 2005;437(7060):884-8.
188. Piel J. Metabolites from Symbiotic Bacteria. Nat Prod Rep. 2009;26(3):338-62.
189. Scott JJ, Oh DC, Yuceer MC, Klepzig KD, Clardy J, Currie CR. Bacterial Protection of Beetle-fungus Mutualism. Science. 2008;322(5898):63.
190. Wenzel SC, Muller R. The Biosynthetic Potential of Myxobacteria and their Impact in Drug Discovery. Curr Opin Drug Discov Dev. 2009;12(2):220-30.
191. Bentley SD, Chater KF, Cerdeño-Tárraga AM, et al. Complete Genome Sequence of the Model Actinomycete Streptomyces coelicolor A3(2). Nature. 2002;417(6885):141-7.
192. Ikeda H, Ishikawa J, Hanamoto A, et al. Complete Genome Sequence and Comparative Analysis of the Industrial Microorganism Streptomyces avermitilis. Nature Biotechnol. 2003;21(5):526-31.
193. Ohnishi Y, Kameyama S, Onaka H, Horinouchi S. The A-factor Regulatory Cascade Leading to Streptomycin Biosynthesis in Streptomyces griseus: Identification of a Target Gene of the A-factor Receptor. Mol Microbiol. 1999;34(1):102-11.
194. Khoklov AS, Tovarova II, Borisova LV, et al. The A-factor, Responsible for Streptomycin Biosynthesis by Mutant Strains of Actinomyces streptomycini. Dokl Akad Nauk SSSR. 1967;177(1):232-5.
195. Horinouchi S. A Microbial Hormone, A-factor, as a Master Switch for Morphological Differentiation and Secondary Metabolism in Streptomyces griseus. Front Biosci. 2002;7:d2045-57.
196. Baltz RH. Streptomyces and Saccharopolyspora Hosts for Heterologous Expression of Secondary Metabolite Gene Clusters. J Ind Microbiol Biotechnol. 2010;37(8): 759-72.
197. Gomez-Escribano JP, Bibb MJ. Engineering Streptomyces coelicolor for Heterologous Expression of Secondary Metabolite Gene Clusters. Microb Biotechnol. 2011;4(2):207-15.
198. Komatsu M, Uchiyama T, Omura S, Cane DE, Ikeda H. Genome-minimized Streptomyces Host for the Heterologous Expression of Secondary Metabolism. Proc Natl Acad Sci USA. 2010;107(6):2646-51.
199. Baltz RH. Strain Improvement in Actinomycetes in the Postgenomic Era. J Ind Microbiol Biotechnol. 2011;38(6):657-66.
200. Rappe MS, Giovannoni SJ. The Uncultured Microbial Majority. Annu Rev Microbiol. 2003;57:369-94.
201. Schloss PD, Handelsman J. Status of the Microbial Census. Microbiol Mol Biol Rev. 2004;68(4):686-91.
202. Freiberg C, Brunner NA, Schiffer G, et al. Identification and Characterization of the First Class of Potent Bacterial Acetyl-CoA Carboxylase Inhibitors with Antibacterial Activity. J Biol Chem. 2004;279(25):26066-73.
203. Needham J, Kelly MT, Ishige M, Andersen RJ. Andrimid and Moiramides A-C, Metabolites Produced in Culture by a Marine Isolate of the Bacterium Pseudomonas fluorescens: Structure Elucidation and Biosynthesis. J Org Chem. 1994;59(8):2058-63.
204. Fredenhagen A, Tamura SY, Kenny PT, et al. Andrimid, a New Peptide Antibiotic Produced by an Intracellular Bacterial Symbiont Isolated from a Brown Planthopper, J Am Chem Soc. 1987;109(14):4409-11.
205. Long RA, Rowley DC, Zamora E, Liu J, Bartlett DH, Azam F. Antagonistic Interactions among Marine Bacteria Impede the Proliferation of Vibrio cholera. Appl Environ Microbiol. 2005;71(12):8531-36.
206. Jin M, Fischbach MA, Clardy J. A Biosynthetic Gene Cluster for the Acetyl-CoA Carboxylase Inhibitor Andrimid. J Am Chem Soc. 2006;128(33):10660-1.
207. Liras P, Martin JF. Gene Clusters for Beta-lactam Antibiotics and Control of their Expression: Why have Clusters Evolved, and from where did they Originate? Int Microbiol. 2006;9(1):9-19.
208. Liras P, Rodriguez-Garcia A, Martin JF. Evolution of the Clusters of Genes for Beta-lactam Antibiotics: A Model for Evolutive Combinatorial Assembly of New Beta-lactams. Int Microbiol. 1998;1(4):271-8.
209. Haste NM, Perera VR, Maloney KN, et al. Activity of the Streptogramin Antibiotic Etamycin Against Methicillin-resistant Staphylococcus aureus. J Antibiot (Tokyo). 2010;63(5):219-24.
210. Li W, Leet JE, Ax HA, et al. Nocathiacins, New Thiazolyl Peptide Antibiotics from Nocardia sp. I. Taxonomy, Fermentation and Biological Activities. J Antibiot (Tokyo). 2003;56(3):226-31.
211. Challis GL. Genome Mining for Novel Natural Product Discovery. J Med Chem. 2008;51(9):2618-28.
212. McAlpine JB. Advances in the Understanding and use of the Genomic Base of Microbial Secondary Metabolite Biosynthesis for the Discovery of New Natural Products. J Nat Prod. 2009;72(3):566-72.
213. Banskota AH, Mcalpine JB, Sørensen D, et al. Genomic Analyses Lead to Novel Secondary Metabolites. Part 3. ECO-0501, a Novel Antibacterial of a New Class. J Antibiot (Tokyo). 2006;59(9):533-42.
214. Wang J, Soisson SM, Young K, et al. Nature 2006;441(7091):358-61.
215. Kohanski MA, Dwyer DJ, Collins JJ. How Antibiotics Kill Bacteria: From Targets to Networks. Nat Rev Microbiol. 2010;8(6):423-35.
216. Markowitz N, Quinn EL, Saravolatz LD. Trimethoprim-sulfamethoxazole Compared with Vancomycin for the Treatment of Staphylococcus aureus Infection. Ann Intern Med. 1992;117(5):390-8.
217. Jemni L, Hmouda H, Letaief A. Efficacy of Trimethoprim-sulfamethoxazole Against Clinical Isolates of Methicillin-resistant Staphylococcus aureus: A Report from Tunisia. Clin Infect Dis. 1994;19(1):202-3.
218. Huovinen P. Resistance to Trimethoprim-sulfamethoxazole. Clin Infect Dis. 2001;32(11):1608-14.
219. Collignon P, Powers JH, Chiller TM, Aidara-Kane A, Aarestrup FM. World Health Organization Ranking of Antimicrobials According to their Importance in Human Medicine: A Critical Step for Developing Risk Management Strategies for the use of Antimicrobials in Food Production Animals. Clin Infect Dis. 2009;49(1): 132-41.
220. Tomasz A. The Mechanism of the Irreversible Antimicrobial Effects of Penicillins: How the Beta-lactam Antibiotics Kill and Lyse Bacteria. Annu Rev Microbiol. 1979;33:113-37.
221. Bassetti M, Ginocchio F, Mikulska M, Taramasso L, Giacobbe DR. Will New Antimicrobials Overcome Resistance among Gram-negatives? Expert Rev Anti Infect Ther. 2011;9(10):909-22.
222. Torres JA, Villegas MV, Quinn JP. Current Concepts in Antibiotic-resistant Gram-negative Bacteria. Expert Rev Anti Infect Ther. 2007;5(5): 833-43.
223. Walsh TR, Toleman MA, Poirel L, Nordmann P. Metallo-beta-lactamases: The Quiet Before the Storm? Clin Microbiol Rev. 2005;18(2):306-25.
224. Nordmann P, Poirel L. Emerging Carbapenemases in Gram-negative Aerobes. Clin Microbiol Infect. 2002;8(6):321-31.
225. Bonomo RA, Szabo D. Mechanisms of Multidrug Resistance in Acinetobacter Species and Pseudomonas aeruginosa. Clin Infect Dis. 2006;43 Suppl(2):S49-56.
226. Navia MM, Ruiz J, Vila J. Characterization of an Integron Carrying a New Class D Beta-lactamase (OXA-37) in Acinetobacter baumannii. Microb Drug Resist. 2002;8(4):261-5.
227. Vila I, Navia M, Ruiz J, Casals C. Cloning and Nucleotide Sequence Analysis of a Gene Encoding an OXA-derived Beta-lactamase in Acinetobacter baumannii. Antimicrob Agents Chemother. 1997;41(12):2757-9.
228. Poirel L, Gerome P, De Champs C, Stephanazzi J, Naas T.Nordmann P, Integron-located oxa-32 Gene Cassette Encoding an Extended-spectrum Variant of OXA-2 Beta-lactamase from Pseudomonas aeruginosa. Antimicrob Agents Chemother.2002;46(2):566-9.
229. Poirel L, Girlich D, Naas T, Nordmann P. OXA-28, an Extended-spectrum Variant of OXA-10 Beta-lactamase from Pseudomonas aeruginosa and its Plasmid- and Integron-located Gene. Antimicrob Agents Chemother. 2001;45:447.
230. Naas T. Nordmann P, OXA-type Beta-lactamases. Curr Pharm Des. 1999;5(11):865-79.
231. Hakenbeck R, Grebe T, Zahner D, Stock JB. Beta-lactam Resistance in Streptococcus pneumoniae: Penicillin-binding Proteins and Non-penicillin-binding Proteins. Mol Microbiol. 1999;33(4):673-8.
232. Chambers HF. Methicillin Resistance in Staphylococci: Molecular and Biochemical Basis and Clinical Implications. Clin Microbiol Rev. 1997;10(4):781-91.
233. Mazzariol A, Cornaglia G, Nikaido H. Contributions of the AmpC Beta-lactamase and the AcrAB Multidrug Efflux System in Intrinsic Resistance of Escherichia coli K-12 to Beta-lactams. Antimicrob. Agents Chemother. 2000;44(5):1387-90.
234. Hancock RE. The Bacterial Outer Membrane as a Drug Barrier. Trends Microbiol. 1997;5(1):37-42.
235. Noel GJ, Bush K, Bagchi P, Ianus J, Strauss RS. A Randomized, Double-blind Trial Comparing Ceftobiprole Medocaril with Vancomycin Plus Ceftazidime for the Treatment of Patients with Complicated Skin and Skin-structure Infections. Clin Infect Dis. 2008;46(5):647-55.
236. El Solh A. Ceftobiprole: A New Broad Spectrum Cephalosporin. Expert Opin Pharmacother. 2009;10(10):1675-86.
237. Takeda S, Nakai T, Wakai T, Ikeda F, Hatano K. In vitro and in vivo Activities of a New Cephalosporin, FR264205, Against Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2007;51(3):826-30.
238. Sader HS, Rhomberg PR, Farrell DJ, Jones RN. Antimicrobial Activity of CXA-101, a Novel Cephalosporin Tested in Combination with Tazobactam Against Enterobacteriaceae, Pseudomonas aeruginosa, and Bacteroides fragilis Strains having Various Resistance Phenotypes. Antimicrob Agents Chemother. 2011;55(5):2390-4.
239. Queenan AM, Shang W, Flamm R, Bush K. Hydrolysis and Inhibition Profiles of Beta-lactamases from Molecular Classes A to D with Doripenem, Imipenem, and Meropenem. Antimicrob. Agents Chemother. 2010;54(1):565-9.
240. Chastre J, Wunderink R, Prokocimer P, Lee M, Kaniga K, Friedland I. Efficacy and Safety of Intravenous Infusion of Doripenem Versus Imipenem in Ventilator-associated Pneumonia: A Multicenter, Randomized Study. Crit Care Med. 2008;36(4):1089-96.
241. Fujimura S, Nakano Y, Sato T, Shirahata K, Watanabe A. Relationship Between the Usage of Carbapenem Antibiotics and the Incidence of Imipenem-resistant Pseudomonas aeruginosa. J Infect Chemother. 2007;13(3):147-50.
242. Livermore DM, Mushtaq S, Warner M. Activity of the Anti-MRSA Carbapenem Razupenem (PTZ601) Against Enterobacteriaceae with Defined Resistance Mechanisms. J Antimicrob Chemother. 2009;64(2):330-5.
243. Page MG, Dantier C, Desarbre E. In vitro Properties of BAL30072, a Novel Siderophore Sulfactam with Activity Against Multiresistant Gram-negative Bacilli. Antimicrob Agents Chemother. 2010;54(6):2291-302.
244. Russo TA, Page MG, Beanan JM, et al. In vivo and in vitro Activity of the Siderophore Monosulfactam BAL30072 Against Acinetobacter baumannii. J Antimicrob Chemother. 2011;66(4):867-73.
245. Kiffer CRV, Sampaio JLM, Sinto S, et al. In vitro Synergy Test of Meropenem and Sulbactam Against Clinical Isolates of Acinetobacter baumannii. Diagn Microbiol Infect Dis. 2005;52(4):317-22.
246. Ehmann DE, Jahic H, Ross PL, et al. Kinetics of Avibactam Inhibition Against Class A, C, and D β-lactamases. J Biol Chem. 2013;288(39):27960-71.
247. Butler MS, Blaskovich MA, Cooper MA. Antibiotics in the Clinical Pipeline in 2013. J Antibio (Tokyo). 2013;66(10):571-91.
248. Bassetti M, Righi E, Viscoli C. Novel Beta-lactam Antibiotics and Inhibitor Combinations. Expert Opin Investig Drugs. 2008;17(3):285-96.
249. Payne DJ, Hueso-Rodríguez JA, Boyd H, et al. Identification of a Series of Tricyclic Natural Products as Potent Broad-spectrum Inhibitors of Metallo-beta-lactamases. Antimicrob Agents Chemother. 2002;46(6):1880-6.
250. Davis BD, Chen LL, Tai PC. Misread Protein Creates Membrane Channels: An Essential Step in the Bactericidal Action of Aminoglycosides. Proc Natl Acad Sci USA. 1986;83(16):6164-8.
251. Wachino J, Shibayama K, Kurokawa H, et al. Novel Plasmid-mediated 16S rRNA m1 A1408 Methyltransferase, NpmA, Found in a Clinically Isolated Escherichia coli Strain Resistant to Structurally Diverse Aminoglycosides. Antimicrob Agents Chemother. 2007;51(12):4401-9.
252. Wachino J, Arakawa Y. Exogenously Acquired 16S rRNA Methyltransferases Found in Aminoglycoside-resistant Pathogenic Gram-negative Bacteria: An Update. Drug Resist Updat. 2012;15(3):133-48.
253. Gillespie SH. Evolution of Drug Resistance in Mycobacterium tuberculosis: Clinical and Molecular Perspective. Antimicrob Agents Chemother. 2002;46(2):267-74.
254. Avent ML, Rogers BA, Cheng AC, Paterson DL. Current use of Aminoglycosides: Indications, Pharmacokinetics and Monitoring for Toxicity. Int Med J. 2011;41(6):441-9.
255. Mingeot-Leclercq MP, Glupczynski Y, Tulkens PM. Aminoglycosides: Activity and Resistance. Antimicrob Agents Chemother. 1999;43(4):727-737.
256. Kawaguchi H, Naito T, Nakagawa S, Fujisawa K. BB-K 8, a New Semisynthetic Aminoglycoside Antibiotic. J Antibio (Tokyo). 1972;25(12):695-708.
257. Lin G, Ednie LM, Appelbaum PC. Antistaphylococcal aActivity of ACHN-490 Tested Alone and in Combination with Other Agents by Time-kill Assay. Antimicrob Agents Chemother. 2010;54(5):2258-61.
258. Pankuch GA, Lin G, Kubo A, Armstrong ES, Appelbaum PC, Kosowska-Shick K. Activity of ACHN-490 Tested Alone and in Combination with Other Agents Against Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2011;55(5):2463-5.
259. Livermore DM, Mushtaq S, Warner M, et al. Activity of Aminoglycosides, Including ACHN-490, Against Carbapenem-resistant Enterobacteriaceae Isolates. J Antimicrob Chemother. 2011;66(1):48-53.
260. Landman D, Kelly P, Bäcker M, et al. Antimicrobial Activity of a Novel Aminoglycoside, ACHN-490, Against Acinetobacter baumannii and Pseudomonas aeruginosa from New York City. J Antimicrob Chemother. 2011;66(2):332-4.
261. Landman D, Babu E, Shah N, et al. Activity of a Novel Aminoglycoside, ACHN-490, Against Clinical Isolates of Escherichia coli and Klebsiella pneumoniae from New York City. J Antimicrob Chemother. 2010;65(10):2123-7.
262. Rahal Jr JJ, Simberkoff MS. Bactericidal and Bacteriostatic Action of Chloramphenicol Against Memingeal Pathogens. Antimicrob Agents Chemother. 1979;16(1):13-8.
263. Falagas ME, Kopterides P. Old Antibiotics for Infections in Critically Ill Patients. Curr Opin Crit Care. 2007;13(5):592-7.
264. Kehrenberg C, Schwarz S, Jacobsen L, Hansen LH, Vester B. A New Mechanism for Chloramphenicol, Florfenicol and Clindamycin Resistance: Methylation of 23S Ribosomal RNA at A2503. Mol Microbiol. 2005;57(4):1064-73.
265. Murray IA, Shaw WV. O-Acetyltransferases for Chloramphenicol and Other Natural Products. Antimicrob Agents Chemother. 1997;41(1):1-6.
266. Arcangioli MA, Leroy-Setrin S, Martel JL, Chaslus-Dancla E. A New Chloramphenicol and Florfenicol Resistance Gene Flanked by Two Integron Structures in Salmonella typhimurium DT104. FEMS Microbiol Lett. 1999;174(2):327-32.
267. Tenson T, Lovmar M, Ehrenberg M. The Mechanism of Action of Macrolides, Lincosamides and Streptogramin B Reveals the Nascent Peptide Exit Path in the Ribosome. J Mol Biol. 2003;330(5):1005-14.
268. Goldstein FW, Emirian MF, Coutrot A, Acar JF. Bacteriostatic and Bactericidal Activity of Azithromycin Against Haemophilus influenzae. J Antimicrob Chemother. 1990;25 Suppl(A):25-8.
269. Liu MF, Douthwaite S. Activity of the Ketolide Telithromycin is Refractory to Erm Monomethylation of Bacterial rRNA. Antimicrob Agents Chemother. 2002;46(6):1629-33.
270. Depardieu F, Courvalin P. Mutation in 23S rRNA Responsible for Resistance to 16-membered Macrolides and Streptogramins in Streptococcus pneumoniae. Antimicrob Agents Chemother. 2001;45(1):319-23.
271. Wittmann HG, Stöffler G, Apirion D, et al. Biochemical and Genetic Studies on Two Different Types of Erythromycin Resistant Mutants of Escherichia coli with Altered Ribosomal Proteins. Mol Gen Genet. 1973;127(2): 175-89.
272. Canu A, Malbruny B, Coquemont M, Davies TA, Appelbaum PC, Leclercq R. Diversity of Ribosomal Mutations Conferring Resistance to Macrolides, Clindamycin, Streptogramin, and Telithromycin in Streptococcus pneumoniae. Antimicrob Agents Chemother. 2002;46(1):125-31.
273. Chesneau O, Tsvetkova K, Courvalin P. Resistance Phenotypes Conferred by Macrolide Phosphotransferases. FEMS Microbiol Lett. 2007;269(2):317-22.
274. Clancy J, Petitpas J, Dib Hajj F, et al. Molecular Cloning and Functional Analysis of a Novel Macrolide-resistance Determinant, mefA, from Streptococcus pyogenes. Mol Microbiol. 1996;22(5):867-79.
275. Moore RA, DeShazer D, Reckseidler S, Weissman A, Woods DE. Efflux-mediated Aminoglycoside and Macrolide Resistance in Burkholderia pseudomallei. Antimicrob Agents Chemother. 1999;43(3):465-470.
276. Hicks LA, Taylor Jr. TH, Hunkler RJ. U.S. Outpatient Antibiotic Prescribing, 2010. N Engl J Med. 2013;368(15):1461-2.
277. Hoban DJ. Prevalence and Characterization of Macrolide Resistance in Clinical Isolates of Streptococcus pneumoniae and Streptococcus pyogenes from North America. J Chemother. 2002;14 Suppl(3):25-30.
278. Echols RM. Understanding the Regulatory Hurdles for Antibacterial Drug Development in the Post-Ketek World. Ann NY Acad Sci. 2011;1241:153-61.
279. Sutcliffe JA. Antibiotics in Development Targeting Protein Synthesis. Ann NY Acad Sci. 2011;1241:122-52.
280. Putnam SD, Sader HS, Farrell DJ, Biedenbach DJ, Castanheira M. Antimicrobial Characterisation of Solithromycin (CEM-101), a Novel Fluoroketolide: Activity Against Staphylococci and Enterococci. Int J Antimicrob Agents. 2011;37(1):39-45.
281. Roberts MC. Update on Acquired Tetracycline Resistance Genes. FEMS Microbiol Lett. 2005;245(2):195-203.
282. Agwuh KN, MacGowan A. Pharmacokinetics and Pharmacodynamics of the Tetracyclines Including Glycylcyclines. J Antimicrob Chemother. 2006;58(2):256-65.
283. Sutcliffe JA, O'Brien W, Fyfe C, Grossman TH. Antibacterial Activity of Eravacycline (TP-434), a Novel Fluorocycline, Against Hospital and Community Pathogens. Antimicrob Agents Chemother. 2013;57(11):5548-58.
284. Grossman TH, Starosta AL, Fyfe C, et al. Target- and Resistance-based Mechanistic Studies with TP-434, a Novel Fluorocycline Antibiotic. Antimicrob Agents Chemother. 2012;56(5):2559-64.
285. Jones CH, Peterson PJ, Tigecycline: A review of Preclinical and Clinical Studies of the First-in-class Glycylcycline Antibiotic. Drugs Today. 2005; 41(10):637-59.
286. Petersen PJ, Jacobus NV, Weiss WJ, Sum PE, Testa RT. In vitro and in vivo Antibacterial Activities of a Novel Glycylcycline, the 9-t-Butylglycylamido Derivative of Minocycline (GAR-936). Antimicrob Agents Chemother. 1999;43(4):738-44.
287. Tasina E, Haidich AB, Kokkali S, Arvanitidou M. Efficacy and Safety of Tigecycline for the Treatment of Infectious Diseases: A Meta-analysis. Lancet Infect Dis. 2011;11(11):834-44.
288. Hornsey M, Ellington MJ, Doumith M, Hudson S, Livermore DM, Woodford N. Tigecycline Resistance in Serratia marcescens Associated with Up-regulation of the SdeXY-HasF Efflux System also Active Against Ciprofloxacin and Cefpirome. J Antimicrob Chemother. 2010;65(3):479-82.
289. Ruzin A, Immermann FW, Bradford PA. RT-PCR and Statistical Analyses of adeABC Expression in Clinical Isolates of Acinetobacter calcoaceticus-Acinetobacter baumannii Complex. Microb Drug Res Mech 2010;16(2):87-9.
290. Horiyama T, Nikaido E, Yamaguchi A, Nishino K. Roles of Salmonella Multidrug Efflux Pumps in Tigecycline Resistance. J Antimicrob Chemother. 2011;66(1):105-10.
291. Peleg AY, Adams J, Paterson DL. Tigecycline Efflux as a Mechanism for Nonsusceptibility in Acinetobacter baumannii. Antimicrob Agents Chemother. 2007;51(6):2065-9.
292. Sensi P. History of the Development of Rifampin. Rev Infect Dis. 1983;5 Suppl(3):S402-6.
293. Almeida Da Silva PE, Palomino JC. Molecular Basis and Mechanisms of Drug Resistance in Mycobacterium tuberculosis: Classical and New Drugs. J Antimicrob Chemother. 2011;66(7):1417-30.
294. Lichtenstein GR, Rifaximin: Recent Advances in Gastroenterology and Hepatology. Gastroenterol Hepatol (NY). 2007;3(6):474-83.
295. Cetinkaya Y, Falk P, Mayhall CG. Vancomycin-resistant Enterococci. Clin Microbiol Rev. 2000;13(4):686-707.
296. Cooper MA, Williams DH. Binding of Glycopeptide Antibiotics to a Model of a Vancomycin-resistant Bacterium. Chem Biol. 1999;6(12):891-9.
297. Kahne D, Leimkuhler C, Lu W, Walsh C. Glycopeptide and Lipoglycopeptide Antibiotics. Chem Rev. 2005;105(2):425-48.
298. Show JP, Seroogy J, Kaniga K, Higgins DL, Kit M, Barriere S. Pharmacokinetics, Serum Inhibitory and Bactericidal Activity, and Safety of Telavancin in Healthy Subjects. Antimicrob Agents Chemother. 2005;49(1):195-201.
299. Pace JL, Yang G, Glycopeptides: Update on an Old Successful Antibiotic Class. Biochem Pharmacol. 2006;71(7):968-80.
300. Barrett JF, Oritavancin. Eli Lilly & Co. Curr Opin Investig Drugs. 2001;2(8):1039-44.
301. Mercier RC, Hrebickova L, Oritavancin: A New Avenue for Resistant Gram-positive Bacteria. Expert Rev Anti Infect Ther. 2005;3(3):325-32.
302. Lin G, Credito K, Ednic LM, Appelbaum PC. Antistaphylococcal Activity of Dalbavancin, an Experimental Glycopeptide. Antimicrob Agents Chemother. 2005;49(2):770-2.
303. Giamarellou H, Treatment Options for Multidrug-resistant Bacteria. Expert Rev Anti Infect Ther. 2006;4(4):601-18.
304. Lambert PA. Mechanisms of Antibiotic Resistance in Pseudomonas aeruginosa. J R Soc Med. 2002;95 Suppl(41):22-6.
305. Hooper DC. Mechanisms of Action and Resistance of Older and Newer Fluoroquinolones. Clin Infect Dis. 2000;31 Suppl(2):S24-8.
306. Robicsek A, Sahm DF, Strahilevitz J, Jacoby GA, Hooper DC. Broader Distribution of Plasmid-mediated Quinolone Resistance in the United States. Antimicrob Agents Chemother. 2005;49(7):3001-3.
307. Nordmann P, Poirel L. Emergence of Plasmid-mediated Resistance to Quinolones in Enterobacteriaceae. J Antimicrob Chemother. 2005;56(3):463-9.
308. Strahilevitz J, Jacoby GA, Hooper DC, Robicsek A. Plasmid-mediated Quinolone Resistance: a Multifaceted Threat. Clin Microbiol Rev. 2009;22(4):664-89.
309. Poole K. Efflux-mediated Resistance to Fluoroquinolones in Gram-negative Bacteria. Antimicrob Agents Chemother. 2000;44(9):2233-41.
310. Oliphant CM, Green GM. Quinolones: A Comprehensive Review. Am Fam Physician. 2002;65(3):455-64.
311. Ambrose PG, Owens Jr RC, Quintiliani R, Nightingale CH. New Generations of Quinolones: With Particular Attention to Levofloxacin. Conn Med. 1997;61(5):269-72.
312. Poole K. Overcoming Antimicrobial Resistance by Targeting Resistance Mechanisms. J Pharm Pharmacol. 2001;53(3):283-94.
313. Lemaire S, Tulkens PM, Van BF. 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. 2011;55(2):649-58.
314. Lauderdale TL, Shiar YR, Lai JF, Chen HC, King CH. Comparative in vitro Activities of Nemonoxacin (TG-873870), a Novel Nonfluorinated Quinolone, and Other Quinolones Against Clinical Isolates. Antimicrob Agents Chemother. 2010;54(3):1338-42.
315. Morrow BJ, He W, Amslem KM, et al. In vitro Antibacterial Activities of JNJ-Q2, a New Broad-spectrum Fluoroquinolone. Antimicrob Agents Chemother. 2010;54(5):1955-64
316. Morrow BJ, Abbanat D, Baum EZ, et al. Antistaphylococcal Activities of the New Fluoroquinolone JNJ-Q2. Antimicrob Agents Chemother. 2011;55(12): 5512-21.
317. Higgins PG, Stubbings W, Wisplinghoff H, Seifert H. Activity of the Investigational Fluoroquinolone Finafloxacin Against Ciprofloxacin-sensitive and -Resistant Acinetobacter baumannii Isolates. Antimicrob Agents Chemother.
318. Merlion Pharmaceuticals. Finafloxacin. Available at: http://www.merlionpharma.com/?q=node/16. Accessed December 20 2013.
319. Roberts MC. Update on Macrolide-lincosamide-streptogramin, Ketolide, and Oxazolidinone Resistance Genes. FEMS Microbiol Lett. 2008;282(2): 147-59.
320. Long KS, Poehlsgaard J, Kehrenberg C, Schwarz S, Vester B. The Cfr rRNA Methyltransferase Confers Resistance to Phenicols, Lincosamides, Oxazolidinones, Pleuromutilins, and Streptogramin A Antibiotics. Antimicrob Agents Chemother. 2006;50(7):2500-5.
321. Smith LK, Mankin AS. Transcriptional and Translational Control of the mlr Operon, which Confers Resistance to Seven Classes of Protein Synthesis Inhibitors. Antimicrob Agents Chemother. 2008;52(5):1703-1712.
322. Koch-Weser J, Sidel VW, Federman EB, Kanarek P, Finer DC, Eaton AE. Adverse Effects of Sodium Colistimethate. Manifestations and Specific Reaction Rates During 317 Courses of Therapy. Ann Intern Med. 1970;72(6): 857-68.
323. Ouderkirk JP, Nord JA, Turett GS, Kislak JW, Polymyxin B. Nephrotoxicity and Efficacy Against Nosocomial Infections Caused by Multiresistant Gram-negative Bacteria. Antimicrob Agents Chemother. 2003;47(8): 2659-62.
324. Michalopoulos AS, Tsiodras S, Rellos K, Mentzelopoulos S, Falagas ME. Colistin Treatment in Patients with ICU-acquired Infections Caused by Multiresistant Gram-negative Bacteria: The Renaissance of an Old Antibiotic. Clin Microbiol Infect. 2005;11(2):115-21.
325. Li J, Nation RL, Milne RW, Turnidge JD, Coulthard K. Evaluation of Colistin as an Agent Against Multi-resistant Gram-negative Bacteria. Int J Antimicrob Agents. 2005;25(1):11-25.
326. Rastogi N, Potar MC, David HL. Antimycobacterial Spectrum of Colistin (Polymixin E). Ann Inst Pasteur Microbiol. 1986;137 A(1):45-53.
327. Gales AC, Jones RN, Sader HS. Global Assessment of the Antimicrobial Activity of Polymyxin B Against 54,731 Clinical Isolates of Gram-negative Bacilli: Report from the SENTRY Antimicrobial Surveillance Programme (2001-2004). Clin Microbiol Infect. 2006;12(4):315-21.
328. Schindler M, Osborn MJ. Interaction of Divalent Cations and Polymyxin B with Lipopolysaccharide. Biochemistry. 1979;18(20):4425-30.
329. Senturk S. Evaluation of the Anti-endotoxic Effects of Polymyxin-E (Colistin) in Dogs with Naturally Occurred Endotoxic Shock. J Vet Pharmacol Ther. 2005;28(1):57-63.
330. Falagas ME, Rafailidis PI, Matthaiou DK. Resistance to Polymyxins: Mechanisms, Frequency and Treatment Options. Drug Resist Update. 2010;13(4-5):132-8.
331. Quale J, Shah N, Kelly P, et al. Activity of Polymyxin B and the Novel Polymyxin Analogue CB-182,804 Against Contemporary Gram-negative Pathogens in New York City. Microb Drug Res. 2012;18(2):132-6.
332. Shapiro S. Speculative Strategies for New Antibacterials: All Roads should not Lead to Rome. J Antibiot (Tokyo). 2013, 66(7):371-86.
333. Vaara M, Fox J, Loidl G, et al. Novel Polymyxin Derivatives Carrying only Three Positive Charges are Effective Antibacterial Agents. Antimicrob Agents Chemother. 2008;52(9):3229-36.
334. Ali FE, Cao G, Poudyal A, et al. Pharmacokinetics of Novel Antimicrobial Cationic Peptides NAB 7061 and NAB 739 in Rats Following Intravenous Administration. J Antimicrob Chemother. 2009;64(5):1067-70.
335. Mingeot-Leclercq MP, Tulkens PM, Denamur S, Vaara T, Vaara M. Novel Polymyxin Derivatives are Less Cytotoxic than Polymyxin B to Renal Proximal Tubular Cells. Peptides. 2012;35(2):248-52.
336. Vaara M, Vaara T. The Novel Polymyxin Derivative NAB739 is Remarkably less Cytotoxic than Polymyxin B and Colistin to Human Kidney Proximal Tubular Cells. Int J Antimicrob Agents. 2013;41(3):292-3.
337. Vaara M, Sader HS, Rhomberg PR, Jones RN, Vaara T. Antimicrobial Activity of the Novel Polymyxin Derivative NAB739 Tested Against Gram-negative Pathogens. J Antimicrob Chemother. 2013;68(3):636-9.
338. Fugitt RB, Luckenbaugh RW. 1978. Patent 4,128,654.
339. Tsiodras S, Gold HS, Sakoulas G, et al. Linezolid Resistance in a Clinical Isolate of Staphylococcus aureus. Lancet. 2001;358(9277):207-08.
340. Shaw KJ, Barbachyn MR. The Oxazolidinones: Past, Present, and Future. Ann NY Acad Sci. 2011;1241:48-70.
341. Morales G, Picazo JJ, Baos E, et al. Resistance to Linezolid is Mediated by the cfr Gene in the First Report of an Outbreak of Linezolid-resistant Staphylococcus aureus. Clin Infect Dis. 2010;50(6):821-5.
342. Seral C, Saenz Y, Algarate S, et al. Nosocomial Outbreak of Methicillin- and Linezolid-resistant Staphylococcus epidermidis Associated with Catheter-related Infections in Intensive Care Unit Patients. Int J Med Microbiol. 2011;301(4):354-8.
343. Gu B, Kelesidis T, Tsiodras S, Hindler J, Humphries RM. The Emerging Problem of Linezolid-resistant Staphylococcus. J Antimicrob Chemother. 2013; 68(1):4-11.
344. Diekema DJ, Jones RN. Oxazolidinone Antibiotics. Lancet. 2001;358(9297): 1975-82.
345. Birmingham MC, Rayner CR, Meagher AK, Flavin SM, Batts DH, Schentag JJ. Linezolid for the Treatment of Multidrug-resistant, Gram-positive Infections: Experience from a Compassionate-use Program. Clin Infect Dis. 2003;36(2):159-68.
346. Bush K. Improving Known Classes of Antibiotics: An Optimistic Approach for the Future. Curr Opin Pharmacol. 2012;12(5):527-34.
347. Rodriguez-Avial I, Culebras E, Betriu C, Morales G, Pena I, Picazo JJ. In vitro Activity of Tedizolid (TR-700) Against Linezolid-resistant Staphylococci. J Antimicrob Chemother. 2012;67(1):167-9.
348. Shaw KJ, Poppe S, Schaadt R, et al. In vitro Activity of TR-700, the Antibacterial Moiety of the Prodrug TR-701, Against Linezolid-resistant Strains. Antimicrob Agents Chemother. 2008;52(12):4442-7.
349. Lawrence L, Danese P, DeVito J, Franceschi F, Sutcliffe JA. In vitro Activities of the Rx-01 Oxazolidinones Against Hospital and Community Pathogens. Antimicrob Agents Chemother. 2008;52(5):1653-62.
350. Locke JB, Finn J, Hilgers M, et al. Structure-activity Relationships of Diverse Oxazolidinones for Linezolid-resistant Staphylococcus aureus Strains Possessing the cfr Methyltransferase Gene or Ribosomal Mutations. Antimicrob Agents Chemother. 2010;54(12):5337-43.
351. Alffenaar JWC, van der Laan T, Simons S, et al. Susceptibility of Clinical Mycobacterium tuberculosis Isolates to a Potentially less Toxic Derivate of Linezolid, PNU-100480. Antimicrob Agents Chemother. 2011;55(3):1287-9.
352. Davlieva M, Zhang W, Arias CA, Shamoo Y. Biochemical Characterization of Cardiolipin Synthase Mutations Associated with Daptomycin Resistance in Enterococci. Antimicrob Agents Chemother. 2013;57(1):289-96.
353. Bertsche U, Yang SJ, Kuehner D, et al. Increased Cell Wall Teichoic Acid Production and D-alanylation are Common Phenotypes Among Daptomycin-resistant Methicillin-resistant Staphylococcus aureus (MRSA) Clinical Isolates. Plos One. 2013;8(6):e67398.
354. Yang SJ, Kreiswirth BN, Sakoulas G, et al. Enhanced Expression of dltABCD is Associated with the Development of Daptomycin Nonsusceptibility in a Clinical Endocarditis Isolate of Staphylococcus aureus. J Infect Dis. 2009;200(12): 1916-20.
355. Yang SJ, Xiong YQ, Dunman PM, et al. Regulation of mprF in Daptomycin-nonsusceptible Staphylococcus aureus Strains. Antimicrob Agents Chemother. 2009;53(6):2636-7.
356. Cubist Pharmaceuticals. Surotomycin (CB-315). Available at: http://www.cubist.com/products/cdad. Accessed December 20 2013.
357. Kadlec K, Pomba CF, Couto N, Schwarz S. Small Plasmids Carrying vga(A) or vga(C) Genes Mediate Resistance to Lincosamides, Pleuromutilins and Streptogramin A Antibiotics in Methicillin-resistant Staphylococcus aureus ST398 from Swine. J Antimicrob Chemother. 2010;65(12):2692-3.
358. Schwendener S, Perreten V. New Transposon Tn6133 in Methicillin-resistant Staphylococcus aureus ST398 Contains vga(E), a Novel Streptogramin A, Pleuromutilin, and Lincosamide Resistance Gene. Antimicrob Agents Chemother. 2011;55(10):4900-4.
359. Miller K, Dunsmore CJ, Colin WG, Chopra I. Linezolid and Tiamulin Cross-resistance in Staphylococcus aureus Mediated by Point Mutations in the Peptidyl Transferase Center. Antimicrob Agents Chemother. 2008;52(5):1737-42.
360. Nabriva Pharmaceuticals. Developing a New Class of Antibiotics. Available at: http://www.nabriva.com/programs/development/. Accessed December 20 2013.
361. Drugs.com. Nabriva Reports Positive Results from Phase II Trial of Pleuromutilin Antibiotic BC-3781 in ABSSSI. Available at: http://www.drugs.com/clinical_trials/nabriva-reports-positive-results-phase-ii-trial-pleuromutilin-antibiotic-bc-3781-absssi-11577.html. Accessed December 20 2013.
362. Srivastava A, Talaue M, Liu S, et al. New Target for Inhibition of Bacterial RNA Polymerase: 'Switch Region'. Curr Opin Microbiol. 2011;14(5):532-43.
363. Louie TJ, Emery J, Krulicki W, Byrne B, Mah M. OPT-80 Eliminates Clostridium difficile and is Sparing of Bacteroides Species During Treatment of C. difficile Infection. Antimicrob Agent Chemother. 2009;53(1):261-3.
364. Andries K, Verhasselt P, Guillemont J, et al. A Diarylquinoline Drug Active on the ATP Synthase of Mycobacterium tuberculosis. Science 2005;307(5707): 223-7.
365. Avorn J. Approval of a Tuberculosis Drug Based on a Paradoxical Surrogate Measure. JAMA. 2013;309(13):1349-50.
366. Ejim L, Farha MA, Falconer SB, et al. Combinations of Antibiotics and Nonantibiotic Drugs Enhance Antimicrobial Efficacy. Nat Chem Biol. 2011;7(6):348-50.
367. Challis GL, Hopwood DA. Synergy and Contingency as Driving Forces for the Evolution of Multiple Secondary Metabolite Production by Streptomyces Species. Proc Natl Acad Sci U.S.A. 2003;100 Suppl(2):14555-61.
368. Rashid MU, Lozano HM, Weintraub A, Nord CE. In vitro Activity of Cadazolid Against Clostridium difficile Strains Isolated from Primary and Recurrent Infections in Stockholm, Sweden. Anaerobe. 2013;20:32-5.
369. Blais J, Lewis SR, Krause KM, Benton BM. Antistaphylococcal Activity of TD-1792, a Multivalent Glycopeptide-cephalosporin Antibiotic. Antimicrob Agents Chemother. 2012;56(3):1584-7.
370. Tyrrell KL, Citron DM, Warren YA, Goldstein EJ. In vitro Activity of TD-1792, a Multivalent Glycopeptide-cephalosporin Antibiotic, Against 377 Strains of Anaerobic Bacteria and 34 Strains of Corynebacterium Species. Antimicrob Agents Chemother. 2012;56(4):2194-7.
371. Pokrovskaya V, Baasov T. Dual-acting Hybrid Antibiotics: A Promising Strategy to Combat Bacterial Resistance. Expert Opin Drug Discov. 2010;5(9): 883-902.
372. Panchal RG, Lane D, Boshoff HI, et al. Bis-imidazolinylindoles are Active against Methicillin-resistant Staphylococcus aureus and Multidrug-resistant Mycobacterium tuberculosis. J. Antibiotics (Japan). 2013;66:47-9.
373. Butler MM, Williams JD, Peet NP, et al. Comparative in Vitro Activity Profiles of Novel Bis-Indole Antibacterials against Gram-Positive and Gram-Negative Clinical Isolates. Antimicrob Agents Chemother. 2010;54(9):3974-7.
374. Huang Q, Kirikae F, Kirikae T, et al. Targeting FtsZ for Antituberculosis Drug Discovery: Noncytotoxic Taxanes as Novel Antituberculosis Agents, J Med Chem. 2006;49(2):463-6.
375. Kumar K, Awasthi D, Lee SY, et al. Novel Trisubstituted Benzimidazoles, Targeting Mtb FtsZ, as a New Class of Antitubercular Agents. J Med Chem. 2011;54(1):374-81.
376. Reynolds RC, Srivastava S, Ross LJ, Suling WJ, White EL. A New 2-Carbomoyl Pteridine that Inhibits Mycobacterial FtsZ. Bioorg Med Chem Lett. 2004;14(12):3161-4.
377. White EL, Suling WJ, Ross LJ, Seitz LE, Reynolds RC. 2-Alkoxycarbonylaminopyridines: Inhibitors of Mycobacterium tuberculosis FtsZ. J Antimicrob Chemother. 2002;50(1):111-4.
378. Matthew B, Ross, L, Reynolds RC. A Novel Quinoline Derivative that Inhibits Mycobacterial FtsZ. Tuberculosis (Oxford, United Kingdom). 2013;93(4): 398-400.
379. Adams DW, Wu LJ, Czaplewski LG, Errington J. Multiple Effects of Benzamide Antibiotics on FtsZ Function. Mol Microbio. 2011;80(1):68-84.
380. Haydon DJ, Stokes NR, Ure R, et al. An Inhibitor of FtsZ with Potent and Selective Anti-staphylococcoal Activity. Science. 2008;321(5896):1673-5.
381. Parhi AK, Zhang Y, Saionz KW, et al. Antibacterial Activity of Quinoxalines, Quinazolines, and 1,5-Naphthyridines. Bioorg Med Chem Lett. 2013;23:4968-74.
382. Kelley C, Zhang Y, Parhi A, Kaul M, Pilch DS, LaVoie EJ. 3-Phenyl Substituted 6,7-Dimethoxyisoquinoline Derivatives as FtsZ-targeting Antibacterial Agents. Bioorg Med Chem Lett. 2012;20(24):7012-29.
383. Kelley C, Lu S, Parhi A, Kaul M, Pilch DS, LaVoie EJ. Antimicrobial Activity of Various 4-and 5-substituted 1-Phenylnaphthalenes. Eur J Med Chem. 2013;60:395-409.
384. Zhang Y, Giurleo D, Parhi A, Kaul M, Pilch DS, LaVoie EJ. Substituted 1,6-Diphenylnaphthalenes as FtsZ-targeting Antibacterial Agents. Bioorg Med Chem Lett. 2013;23(7):2001-6.
385. Margalit DN, Romberg L, Mets RB, et al. Targeting Cell Division: Small-molecule Inhibitors of FtsZ GTPase Perturb Cytokinetic Ring Assembly and Induce Bacterial Lethality. Proc. Nat. Acad. Sci. (USA). 2004;101(32):11821-6.
386. Haydon DJ, Bennett JM, Brown D, et al. Creating an Antibacterial with in vivo Efficacy: Synthesis and Characterization of Potent Inhibitors of the Bacterial Cell Division Protein FtsZ with Improved Pharmaceutical Properties. J Med Chem. 2010;53(10):3927-36.
387. Plaza A, Keffer JL, Bifulco G, Lloyd JR, Bewley CA. Chrysophaentins A-H, Antibacterial Bisdiarylbutene Macrocycles that Inhibit the Bacterial Cell Division Protein FtsZ. J Am Chem Soc. 2010;132(26):9069-77.
388. Urgaonkar S, La Pierre HS, Meir I, Lund H, RayChaudhuri D, Shaw JT. Synthesis of Antimicrobial Natural Products Targeting FtsZ: (+/-)-Dichamanetin and (+/-)-2' -hydroxy-5' -Benzylisouvarinol-B. Org Lett. 2005;7(25): 5609-12.
389. Parhi A, Kelley C, Kaul M, Pilch DS, LaVoie EJ. Antibacterial Activity of Substituted 5-Methylbenzo[c]phenanthridinium Derivatives. Bioorg Med Chem Lett. 2012;22(23):7080-3.
390. Wang J, Galgoci A, Kodali S, et al. Discovery of a Small Molecule that Inhibits Cell Division by Blocking FtsZ, a Novel Therapeutic Target of Antibiotics. J Biol Chem. 2003;278(45):44424-44428.
391. Paradis-Bleau C, Beaumont M, Sanschagrin F, Voyer N, Levesque RC. Parallel Solid Synthesis of Inhibitors of the Essential Cell Division FtsZ Enzyme as a New Potential Class of Antibacterials. Bioorg Med Chem. 2007;15(3):1330-40.
392. Sass P, Josten M, Famulla K, et al. Antibiotic Acyldepsipeptides Activate ClpP Peptidase to Degrade the Cell Division Protein FtsZ. Proc Nat Acad Sci (USA). 2011;42(108):17474-9.
393. Brötz-Oesterhelt H, Beyer D, Kroll HP, et al. Dysregulation of Bacterial Proteolytic Machinery by a New Class of Antibiotics. Nat Med. 2005;11(10):1082-7.
394. Hinzen B, Raddatz S, Paulsen H, et al. Medicinal Chemistry Optimization of Acyldepsipeptides of the Enopeptin Class Antibiotics. Chem Med Chem. 2006;1(7):689-93.
395. Johnson KW, Lofland D, Moser HE. PDF Inhibitors: An Emerging Class of Antibacterial Drugs. Curr Drug Targets Infect Disord. 2005;5(1):39-52.
396. Aubart K, Zalacain M. Peptide Deformylase Inhibitors. Prog Med Chem. 2006;44:109-143.
397. Lofland D, Difuntorum S, Waller A, et al. In vitro Antibacterial Activity of the Peptide Deformylase Inhibitor BB-83698. J Antimicrob Chemother. 2004;53(4):664-8.
398. Fritsche TR, Sader HS, Cleeland R, Jones RN. Comparative Antimicrobial Characterization of LBM415 (NVP PDF-713), a New Peptide Deformylase Inhibitor of Clinical Importance. Antimicrob Agents Chemother. 2005;49(4):1468-76.
399. O'Dwyer K, Hackel M, Hightower S, et al. Comparative Analysis of the Antibacterial Activity of a Novel Peptide Deformylase Inhibitor, GSK1322322. Antimicrob Agents Chemother. 2013;57(5):2333-42.
400. Bister B, Bischoff D, Ströbele M, et al. Abyssomicin C-A Polycyclic Antibiotic from a Marine Verrucosispora Strain as an Inhibitor of the p-Aminobenzoic acid/Tetrahydrofolate Biosynthesis Pathway. Angew Chem Int Ed. 2004;43(19):2574-2576.
401. Riedlinger J, Reicke A, Zähner H, et al. Abyssomicins, Inhibitors of the Para-aminobenzoic Acid Pathway Produced by the Marine Verrucosispora Strain AB-18-032. J Antibiot (Tokyo). 2004;57(4):271-9.
402. Keller S, Schadt HS, Ortel I, Süssmuth RD. Action of Atrop-abyssomicin C as an Inhibitor of 4-Amino-4-deoxychorismate Synthase PabB. Angew Chem Int Ed. 2007;46(43):8284-6.
403. Fisher M, Basak R, Kalverda AP, Fishwick CW, Turnbull WB, Nelson A. Discovery of Novel FabF Ligands Inspired by Platensimycin by Integrating Structure-based Design with Diversity-oriented Synthetic Accessibility. Org Biomol Chem. 2014;12(3):486-94.
404. Ghosh AK, Xi K. A Symmetry-based Concise Formal Synthesis of Platencin, a Novel Lead against "Superbugs". Angew Chem Int Ed. 2009;48 (29): 5372-5.
405. Martens E, Demain AL. Platensimycin and Platencin: Promising Antibiotics for Future Application in Human Medicine. J Antibiot (Tokyo). 2011;64(11):705-10.
406. Wang J, Lee V, Sintim HO. Efforts Towards the Identification of Simpler Platensimycin Analogues: The Total Synthesis of Oxazinidinyl Platensimycin. Chemistry. 2009;15(12):2747-50.
407. Nicolaou KC, Stepan AF, Lister T, et al. Design, Synthesis, and Biological Evaluation of Platensimycin Analogues with Varying Degrees of Molecular Complexity. J Am Chem Soc. 2008;130(39):13110-9.
408. Shen HC, Ding FX, Singh SB, et al. Synthesis and Biological Evaluation of Platensimycin Analogs. Bioorg Med Chem Lett. 2009;19(6):1623-7.
409. Nicolaou KC, Tang Y, Wang J, Stepan AF, Li A, Montero A. Total Synthesis and Antibacterial Properties of Carbaplatensimycin. J Am Chem Soc. 2007;129(48):14850-1.
410. Nicolaou KC, Lister T, Denton RM, Montero A, Edmonds DJ. Adamantaplatensimycin: A Bioactive Analogue of Platensimycin. Angew Chem Int Ed. 2007;46(25):4712-4.
411. Young K, Jayasuriya H, Ondeyka JG, et al. Discovery of FabH/FabF Inhibitors from Natural Products. Antimicrob Agents Chemother. 2006; 50(2):519-26.
412. Wang J, Soisson SM, Young K, et al. Platensimycin is a Selective FabF Inhibitor with Potent Antibiotic Properties. Nature. 2006;441(7091): 358-61.
413. Singh SB, Jayasuriya H, Ondeyka JG, et al. Isolation, Structure, and Absolute Stereochemistry of Platensimycin, a Broad Spectrum Antibiotic Discovered using an Antisense Differential Sensitivity Strategy. J Am Chem Soc. 2006;128(36):11916-20.
414. Wang J, Kodali S, Lee SH, et al. Discovery of Platencin, a Dual FabF and FabH Inhibitor with in vivo Antibiotic Properties. Proc Natl Acad Sci. 2007;104(18):7612-16.
415. Jayasuriya H, Herath KB, Zhang C, et al. Isolation and Structure of Platencin: a FabH and FabF Dual Inhibitor with Potent Broad-spectrum Antibiotic Activity. Angew Chem Int Ed 2007;46(25): 4684-8.
416. Allahverdiyev AM, Bagirova M, Abamor ES, et al. The use of Platensimycin and Platencin to Fight Antibiotic Resistance. Infect Drug Res. 2013;6:99-114.
417. Claesson A, Jansson AM, Pring BG, Hammond SM, Ekström B. Design and Synthesis of Peptide Derivatives of a 3-Deoxy-D-manno-2-octulosonic acid (KDO) Analogue as Novel Antibacterial Agents Acting upon Lipopolysaccharide Biosynthesis. J Med Chem. 1987;30(12):2309-13.
418. Cipolla L, Polissi A, Airoldi C, Galliani P, Sperandeo P, Nicotra F. The Kdo Biosynthetic Pathway toward OM Biogenesis as Target in Antibacterial Drug Design and Development. Curr Drug Discov Technol. 2009;6(1):19-33.
419. Cipolla L, Polissi A, Airoldi C, Gabrielli L, Merlo S, Nicotra F. New Targets for Antibacterial Design: Kdo Biosynthesis and LPS Machinery Transport to the Cell Surface. Curr Med Chem. 2011;18(6):830-52.
420. Kaustov L, Kababya S, Belakhov V, Baasov T, Shoham Y, Schmidt A. Inhibition Mode of a Bisubstrate Inhibitor of KDO8P Synthase: A Frequency-selective REDOR Solid-state and Solution NMR Characterization. J Am Chem Soc. 2003;125(15):4662-9.
421. Belakhov V, Dovgolevsky E, Rabkin E, Shulami S, Shoham Y, Baasov T. Synthesis and Evaluation of a Mechanism-based Inhibitor of KDO8P Synthase. Carbohydr Res. 2004;339(2):385-92.
422. Coutrot P, Dumarçay S, Finance C, Tabyaoui M, Tabyaoui B, Grison C. Investigation of New Potent KDO-8-phosphate Synthetase Inhibitors. Bioorg Med Chem Lett. 1999;9(7):949-52.
423. Baasov T, Sheffer-Dee-Noor S, Kohen A, Jakob A, Belakhov V. Catalytic Mechanism of 3-Deoxy-D-manno-2-octulosonate-8-phosphate Synthase. The use of Synthetic Analogues to Probe the Structure of the Putative Reaction Intermediate. Eur J Biochem. 1993;217(3):991-9.
424. Adachi H, Kondo K, Kojima F, et al. Synthesis and Inhibitory Activity of 8-Substituted 2-Deoxy-beta-KDO against CMP-KDO Synthetase. Nat Prod Res. 2006;20(4):361-370.
425. Goldstein EJ, Citron DM, Tyrrell KL, Merriam CV. Comparative in vitro Activities of GSK2251052, a Novel Boron-containing Leucyl-tRNA Synthetase Inhibitor, against 916 Anaerobic Organisms. Antimicrob Agents Chemother. 2013;57(5):2401-4.
426. Mendez RE, Biedenbach DJ, Alley MRK, Sader HS, Jones RN, 2011. Potency and Spectrum of Activity of AN3365, a Novel Boron-containing Protein Synthesis Inhibitor, Tested against Enterobacteriaceae, abstr F1-1638. Fifty-first Intersci. Conf. Antimicrob. Agents Chemother., Chicago, IL, 17 to 20 September 2011.
427. Robertson JG. Enzymes as a Special Class of Therapeutic Target: Clinical Drugs and Modes of Action. Curr Opin Struct Biol. 2007;17:674-9.