Antibiotic resistance in Enterobacteriaceae: Mechanisms and clinical implications

BMJ (Online)

Volumn 352, Issue , 2016, Pages

  Iredell, Jon ^a   Brown, Jeremy ^b   Tagg, Kaitlin ^a  

^a University of Sydney   (Australia)

^b Western Sydney Area Health Service   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

AMINOGLYCOSIDE ANTIBIOTIC AGENT; AVIBACTAM; CARBAPENEM DERIVATIVE; CEPHALOSPORIN DERIVATIVE; COLISTIMETHATE; ERAVACYCLINE; EXTENDED SPECTRUM BETA LACTAMASE; FOSFOMYCIN; PENICILLIN DERIVATIVE; PLAZOMICIN; POLYPEPTIDE ANTIBIOTIC AGENT; QUINOLINE DERIVED ANTIINFECTIVE AGENT; TIGECYCLINE; ANTIINFECTIVE AGENT; BACTERIAL PROTEIN;

ACCESSORY GENOME; ANIMAL HUSBANDRY; ANTIBIOTIC RESISTANCE; BACTERIAL GENE; BACTERIAL GENOME; BACTERIAL MEMBRANE; BACTERIAL TRANSMISSION; BACTERIOPHAGE; BACTERIOTHERAPY; BIOLOGICAL THERAPY; CLONE; DISINFECTION; DRUG MODIFICATION; DRUG SURVEILLANCE PROGRAM; ENTEROBACTERIACEAE; GENE POOL; GENETIC VARIABILITY; GRAM NEGATIVE BACTERIUM; GRAM POSITIVE BACTERIUM; HEALTH SURVEY; HOSPITAL WASTE; HUMAN; INCIDENCE; INFECTION CONTROL; KLEBSIELLA PNEUMONIAE; LYTIC BACTERIOPHAGE; NONHUMAN; PHARMACOKINETIC PARAMETERS; PLASMID; PLASTICITY; PRACTICE GUIDELINE; PREVALENCE; PRIORITY JOURNAL; REVIEW; DRUG EFFECTS; ENTEROBACTERIACEAE INFECTIONS; GENETIC VARIATION; GENETICS; MICROBIOLOGY; PHYSIOLOGY;

ANTI-BACTERIAL AGENTS; BACTERIAL PROTEINS; DRUG RESISTANCE, BACTERIAL; ENTEROBACTERIACEAE; ENTEROBACTERIACEAE INFECTIONS; GENETIC VARIATION; HUMANS;

EID: 84960171635     PISSN: 09598146     EISSN: 17561833     Source Type: Journal    
DOI: 10.1136/bmj.h6420     Document Type: Review

References (260)

1. Iredell J, Thomas L, Power D, et al. Tigecycline resistance in Australian antibioticresistant Gram-negative bacteria. J Antimicrob Chemother 2007;59:816-18.
2. Sommer MO, Dantas G, Church GM. Functional characterization of the antibiotic resistance reservoir in the human microflora. Science 2009;325:1128-31.
3. Forsberg KJ, Reyes A, Wang B, et al. The shared antibiotic resistome of soil bacteria and human pathogens. Science 2012;337:1107-11
4. Bhullar K, Waglechner N, Pawlowski A, et al. Antibiotic resistance is prevalent in an isolated cave microbiome. PLoS One 2012;7:e34953.
5. WHO. Antimicrobial resistance: Global report on surveillance, 2014. http://apps.who.int/iris/bitstream/10665/112642/1/9789241564748-eng.pdf.
6. Geser N, Stephan R, Korczak BM, et al. Molecular identification of extendedspectrum-?-lactamase genes from Enterobacteriaceaeisolated from healthy human carriers in Switzerland. Antimicrob Agents Chemother 2012;56:1609-12.
7. Lonchel CM, Meex C, Gangoué-Piéboji J, et al. Proportion of extendedspectrum ß-lactamase-producing Enterobacteriaceae in community setting in Ngaoundere, Cameroon. BMC Infect Dis 2012;12:53.
8. Castanheira M, Farrell SE, Deshpande LM, et al. Prevalence of ?-lactamaseencoding genes among Enterobacteriaceaebacteremia isolates collected in 26 US hospitals: Report from the SENTRY antimicrobial surveillance program (2010). Antimicrob Agents Chemother 2013;57:3012-20.
9. Rossi F, Baquero F, Hsueh PR, et al. In vitro susceptibilities of aerobic and facultatively anaerobic Gram-negative bacilli isolated from patients with intra-abdominal infections worldwide: 2004 results from SMART (Study for Monitoring Antimicrobial Resistance Trends). J Antimicrob Chemother 2006;58:205-10.
10. Paterson DL, Rossi F, Baquero F, et al. In vitro susceptibilities of aerobic and facultative Gram-negative bacilli isolated from patients with intra-abdominal infections worldwide: The 2003 Study for Monitoring Antimicrobial Resistance Trends (SMART). J Antimicrob Chemother 2005;55:965-73.
11. Hawser SP, Bouchillon SK, Hoban DJ, et al. Epidemiologic trends, occurrence of extended-spectrum ?-lactamase production, and performance of ertapenem and comparators in patients with intra-abdominal infections: Analysis of global trend data from 2002-2007 from the SMART study. Surg Infect 2010;11:371-8.
12. Brink AJ, Botha RF, Poswa X, et al. Antimicrobial susceptibility of gram-negative pathogens isolated from patients with complicated intra-abdominal infections in South African hospitals (SMART Study 2004-2009): Impact of the new carbapenem breakpoints. Surg Infect 2012;13:43-9.
13. Yang Q, Zhang H, Wang Y, et al. A 10 year surveillance for antimicrobial susceptibility of Escherichia coli and Klebsiella pneumoniaein community-and hospital-associated intra-abdominal infections in China. J Med Microbiol 2013;62(pt 9):1343-9.
14. Zhang H, Yang Q, Xiao M, et al. Antimicrobial susceptibility of Gramnegative bacteria causing intra-abdominal infections in China: SMART China 2011. Chin Med J (Engl) 2014;127:2429-33.
15. Yang Q, Wang H, Chen M, et al. Surveillance of antimicrobial susceptibility of aerobic and facultative Gram-negative bacilli isolated from patients with intra-abdominal infections in China: The 2002-2009 Study for Monitoring Antimicrobial Resistance Trends (SMART). Int J Antimicrob Agents 2010;36:507-12.
16. Hoban DJ, Bouchillon SK, Hawser SP, et al. Susceptibility of gram-negative pathogens isolated from patients with complicated intra-abdominal infections in the United States, 2007-2008: Results of the Study for Monitoring Antimicrobial Resistance Trends (SMART). Antimicrob Agents Chemother 2010;54:3031-4.
17. Hoban DJ, Lascols C, Nicolle LE, et al. Antimicrobial susceptibility of Enterobacteriaceae, including molecular characterization of extendedspectrum ?-lactamase-producing species, in urinary tract isolates from hospitalized patients in North America and Europe: Results from the SMART study 2009-2010. Diagn Microbiol Infect Dis 2012;74:62-7.
18. Ko WC, Hsueh PR. Increasing extended-spectrum ?-lactamase production and quinolone resistance among Gram-negative bacilli causing intraabdominal infections in the Asia/Pacific region: Data from the Smart Study 2002-2006. J Infect 2009;59:95-103.
19. Hsueh PR, Snyder TA, Dinubile MJ, et al. In vitro susceptibilities of aerobic and facultative Gram-negative bacilli isolated from patients with intraabdominal infections in the Asia-Pacific region: 2004 results from SMART (Study for Monitoring Antimicrobial Resistance Trends). Int J Antimicrob Agents 2006;28:238-43.
20. Hawser S, Hoban D, Bouchillon S, et al. Antimicrobial susceptibility of intra-abdominal gram-negative bacilli from Europe: SMART Europe 2008. Eur J Clin Microbiol Infect Dis 2011;30:173-9.
21. Villegas MV, Blanco MG, Sifuentes-Osornio J, et al. Increasing prevalence of extended-spectrum-?-lactamase among Gram-negative bacilli in Latin America-2008 update from the Study for Monitoring Antimicrobial Resistance Trends (SMART). Braz J Infect Dis 2011;15:34-9.
22. Baquero F, Hsueh PR, Paterson DL, et al. In vitro susceptibilities of aerobic and facultatively anaerobic gram-negative bacilli isolated from patients with intra-abdominal infections worldwide: 2005 results from Study for Monitoring Antimicrobial Resistance Trends (SMART). Surg Infect 2009;10:99-104.
23. Lu PL, Liu YC, Toh HS, et al. Epidemiology and antimicrobial susceptibility profiles of Gram-negative bacteria causing urinary tract infections in the Asia-Pacific region: 2009-2010 results from the Study for Monitoring Antimicrobial Resistance Trends (SMART). Int J Antimicrob Agents 2012;40(suppl):S37-43.
24. Hawser SP, Bouchillon SK, Hoban DJ, et al. In vitro susceptibilities of aerobic and facultative anaerobic Gram-negative bacilli from patients with intra-abdominal infections worldwide from 2005-2007: Results from the SMART study. Int J Antimicrob Agents 2009;34:585-8.
25. Hawser SP, Bouchillon SK, Lascols C, et al. Susceptibility of European Escherichia coli clinical isolates from intra-abdominal infections, extended-spectrum ?-lactamase occurrence, resistance distribution, and molecular characterization of ertapenem-resistant isolates (SMART 2008-2009). Clin Microbiol Infect 2012;18:253-9.
26. Chow JW, Satishchandran V, Snyder TA, et al. In vitro susceptibilities of aerobic and facultative gram-negative bacilli isolated from patients with intra-abdominal infections worldwide: The 2002 Study for Monitoring Antimicrobial Resistance Trends (SMART). Surg Infect 2005;6:439-48.
27. Mendes RE, Mendoza M, Banga Singh KK, et al. Regional resistance surveillance program results for 12 Asia-Pacific nations (2011). Antimicrob Agents Chemother 2013;57:5721-6.
28. Hilty M, Betsch BY, Bögli-Stuber K, et al. Transmission dynamics of extended-spectrum ?-lactamase-producing Enterobacteriaceae in the tertiary care hospital and the household setting. Clin Infect Dis 2012;55:967-75.
29. Adler A, Shklyar M, Schwaber MJ, et al. Introduction of OXA-48-producing Enterobacteriaceae to Israeli hospitals by medical tourism. J Antimicrob Chemother 2011; published online 19 Sep; doi:10.1093/jac/dkr382.
30. Poirel L, Naas T, Nordmann P. Diversity, epidemiology, and genetics of class D ?-lactamases. Antimicrob Agents Chemother 2010;54:24-38.
31. Wendt C, Schütt S, Dalpke AH, et al. First outbreak of Klebsiella pneumoniae carbapenemase (KPC)-producing K pneumoniae in Germany. Eur J Clin Microbiol Infect Dis 2010;29:563-70.
32. Doi Y, Park YS, Rivera JI, et al. Community-associated extended-spectrum ?-lactamase-producing Escherichia coli infection in the United States. Clin Infect Dis 2013;56:641-8.
33. Lagacé-Wiens PR, Adam HJ, Low DE, et al. Trends in antibiotic resistance over time among pathogens from Canadian hospitals: Results of the CANWARD study 2007-11. J Antimicrob Chemother 2013;68(suppl 1):i23-9.
34. Turnidge JD, Gottlieb T, Mitchell DH, et al. Community-onset Gramnegative Surveillance Program annual report, 2012. Commun Dis Intell Q Rep 2014;38:E54-8.
35. Turnidge JD, Gottlieb T, Mitchell DH, et al. Australian Group on Antimicrobial Resistance Community-onset Gram-negative Surveillance Program annual report, 2010. Commun Dis Intell Q Rep 2013;37:E219-23.
36. Yong D, Toleman MA, Giske CG, et al. Characterization of a new metallo-?-lactamase gene, blaNDM-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;53:5046-54.
37. Rogers BA, Aminzadeh Z, Hayashi Y, et al. Country-to-country transfer of patients and the risk of multi-resistant bacterial infection. Clin Infect Dis 2011;53:49-56.
38. Tängdén T, Cars O, Melhus Å, et al. Foreign travel is a major risk factor for colonization with Escherichia coli producing CTX-M-type extendedspectrum ?-lactamases: A prospective study with Swedish volunteers. Antimicrob Agents Chemother 2010;54:3564-8.
39. Von Wintersdorff CJH, Penders J, Stobberingh EE, et al. High rates of antimicrobial drug resistance gene acquisition after international travel, the Netherlands. Emerg Infect Dis 2014;20:649-57.
40. Vento TJ, Cole DW, Mende K, et al. Multidrug-resistant Gram-negative bacteria colonization of healthy US military personnel in the US and Afghanistan. BMC Infect Dis 2013;13:1-11.
41. Shitrit P, Reisfeld S, Paitan Y, et al. Extended-spectrum ?-lactamaseproducing Enterobacteriaceae carriage upon hospital admission: Prevalence and risk factors. J Hosp Infect 2013;85:230-32.
42. Rooney PJ, O'Leary MC, Loughrey AC, et al. Nursing homes as a reservoir of extended-spectrum ?-lactamase (ESBL)-producing ciprofloxacin-resistant Escherichia coli. J Antimicrob Chemother 2009;64:635-41.
43. Luvsansharav UO, Hirai I, Niki M, et al. Fecal carriage of CTX-M ?-lactamase-producing Enterobacteriaceae in nursing homes in the Kinki region of Japan. Infect Drug Resist 2013;6:67-70.
44. Oteo J, Navarro C, Cercenado E, et al. Spread of Escherichia coli strains with high-level cefotaxime and ceftazidime resistance between the community, long-term care facilities, and hospital institutions. J Clin Microbiol 2006;44:2359-66.
45. O'Fallon E, Kandel R, Schreiber R, et al. Acquisition of multidrug-resistant Gram-negative bacteria: Incidence and risk factors within a long-term care population. Infect Control Hosp Epidemiol 2010;31:1148-53.
46. Lohiya A, Kant S, Kapil A, et al. Pattern of antibiotic resistance among community derived isolates of enterobacteriaceae using urine sample: A study from northern India. J Clin Diagnost Res 2015;9:LC15-9.
47. Diwan V, Tamhankar AJ, Khandal RK, et al. Antibiotics and antibioticresistant bacteria in waters associated with a hospital in Ujjain, India. BMC Public Health 2010;10:414.
48. Amos GCA, Hawkey PM, Gaze WH, et al. Waste water effluent contributes to the dissemination of CTX-M-15 in the natural environment. J Antimicrob Chemother 2014;69:1785-91.
49. Chen B, Zheng W, Yu Y, et al. Class 1 integrons, selected virulence genes, and antibiotic resistance in Escherichia coli isolates from the Minjiang River, Fujian Province, China. Appl Environ Microbiol 2011;77:148-55.
50. De Boeck H, Miwanda B, Lunguya-Metila O, et al. ESBL-positive Enterobacteriaisolates in drinking water [letter]. Emerg Infect Dis 2012;18:1019-20.
51. Coleman BL, Louie M, Salvadori MI, et al. Contamination of Canadian private drinking water sources with antimicrobial resistant Escherichia coli. Water Res 2013;47:3026-36.
52. Kamruzzaman M, Shoma S, Bari SMN, et al. Genetic diversity and antibiotic resistance in Escherichia coli from environmental surface water in Dhaka city, Bangladesh. Diagn Microbiol Infect Dis 2013;76:222-6.
53. Talukdar PK, Rahman M, Rahman M, et al. Antimicrobial resistance, virulence factors and genetic diversity of Escherichia coli isolates from household water supply in Dhaka, Bangladesh. PLoS One 2013;8:e61090.
54. Dhanji H, Murphy NM, Akhigbe C, et al. Isolation of fluoroquinoloneresistant O25b:H4-ST131 Escherichia coli with CTX-M-14 extendedspectrum ?-lactamase from UK river water. J Antimicrob Chemother 2011;66:512-6.
55. Leverstein-van Hall MA, Dierikx CM, Cohen Stuart J, et al. Dutch patients, retail chicken meat and poultry share the same ESBL genes, plasmids and strains. Clin Microbiol Infect 2011;17:873-80.
56. Schmid A, Hörmansdorfer S, Messelhäusser U, et al. Prevalence of extended-spectrum ?-lactamase-producing Escherichia coli on Bavarian dairy and beef cattle farms. Appl Environ Microbiol 2013;79:3027-32.
57. Sahoo KC, Tamhankar AJ, Sahoo S, et al. Geographical variation in antibiotic-resistant Escherichia coli isolates from stool, cow-dung and drinking water. Int J Environ Res Public Health 2012;9:746-59.
58. Frye JG, Jackson CR. Genetic mechanisms of antimicrobial resistance identified in Salmonella enterica, Escherichia coli, and Enteroccocus spp isolated from US food animals. Front Microbiol 2013;4:135.
59. Geser N, Stephan R, Hächler H. Occurrence and characteristics of extended-spectrum ?-lactamase (ESBL) producing Enterobacteriaceae in food producing animals, minced meat and raw milk. BMC Vet Res 2012;8:21.
60. Horton RA, Randall LP, Snary EL, et al. Fecal carriage and shedding density of CTX-M extended-spectrum ?-lactamase-producing Escherichia coli in cattle, chickens, and pigs: Implications for environmental contamination and food production. Appl Environ Microbiol 2011;77:3715-19.
61. Rodriguez-Lazaro D, Ariza-Miguel J, Diez-Valcarce M, et al. Identification and molecular characterization of pathogenic bacteria in foods confiscated from non-EU flights passengers at one Spanish airport. Int J Food Microbiol 2015;209:20-5.
62. Schmiedel J, Falgenhauer L, Domann E, et al. Multiresistant extendedspectrum ?-lactamase-producing Enterobacteriaceaefrom humans, companion animals and horses in central Hesse, Germany. BMC Microbiol 2014;14:1471-2180.
63. Timofte D, Dandrieux J, Wattret A, et al. Detection of extended-spectrum-?-lactamase-positive Escherichia coli in bile isolates from two dogs with bacterial cholangiohepatitis. J Clin Microbiol 2011;49:3411-4.
64. Guenther S, Ewers C, Wieler LH. Extended-spectrum ?-lactamases producingE coli in wildlife, yet another form of environmental pollution? Front Microbiol 2011;2:246.
65. Hasan B, Sandegren L, Melhus A, et al. Antimicrobial drug-resistant Escherichia coli in wild birds and free-range poultry, Bangladesh. Emerg Infect Dis 2012;18:2055-8.
66. Hernandez J, Johansson A, Stedt J, et al. Characterization and comparison of extended-spectrum ?-lactamase (ESBL) resistance genotypes and population structure of Escherichia coli isolated from Franklin's Gulls (Leucophaeus pipixcan) and humans in Chile. PLoS One 2013;8:e76150.
67. Hasan B, Melhus A, Sandegren L, et al. The gull (Chroicocephalus brunnicephalus) as an environmental bioindicator and reservoir for antibiotic resistance on the coastlines of the Bay of Bengal. Microb Drug Resist 2014;30:30.
68. Turnidge J, Paterson DL. Setting and revising antibacterial susceptibility breakpoints. Clin Microbiol Rev 2007;20:391-408.
69. Mouton JW, Brown DF, Apfalter P, et al. The role of pharmacokinetics/pharmacodynamics in setting clinical MIC breakpoints: The EUCAST approach. Clin Microbiol Infect 2012;18:E37-45.
70. Turnidge J, Kahlmeter G, Kronvall G. Statistical characterisation of bacterial wild-type MIC value distributions and the determination of epidemiological cut-off values. Clin Microbiol Infect 2006;12:418-25.
71. Martinez JL, Coque TM, Baquero F. What is a resistance gene? Ranking risk in resistomes. Nat Rev Microbiol 2015;13:116-23.
72. Kester JC, Fortune SM. Persisters and beyond: Mechanisms of phenotypic drug resistance and drug tolerance in bacteria. Crit Rev Biochem Mol Biol 2014;49:91-101.
73. Stewart PS, Costerton JW. Antibiotic resistance of bacteria in biofilms. Lancet 2001;358:135-8.
74. Kotte O, Volkmer B, Radzikowski JL, et al. Phenotypic bistability in Escherichia coli's central carbon metabolism. Mol Syst Biol 2014;10:736.
75. Arnoldini M, Vizcarra IA, Peña-Miller R, et al. Bistable expression of virulence genes in Salmonella leads to the formation of an antibiotictolerant subpopulation. PLoS Biol 2014;12:e1001928.
76. Ferenci T, Maharjan R. Mutational heterogeneity: A key ingredient of bethedging and evolutionary divergence? Bioessays 2015;37:123-30.
77. Maharjan R, Seeto S, Notley-McRobb L, et al. Clonal adaptive radiation in a constant environment. Science 2006;313:514-7.
78. Beardmore RE, Gudelj I, Lipson DA, et al. Metabolic trade-offs and the maintenance of the fittest and the flattest. Nature 2011;472:342-6.
79. Li XZ, Plesiat P, Nikaido H. The challenge of efflux-mediated antibiotic resistance in Gram-negative bacteria. Clin Microbiol Rev 2015;28:337-418.
80. Sato K, Nakae T. Outer membrane permeability of Acinetobacter calcoaceticus and its implication in antibiotic resistance. J Antimicrob Chemother 1991;28:35-45.
81. Fernández L, Hancock RE. Adaptive and mutational resistance: Role of porins and efflux pumps in drug resistance. Clin Microbiol Rev 2012;25:661-81.
82. Nikaido H, Pagès JM. Broad-specificity efflux pumps and their role in multidrug resistance of Gram-negative bacteria. FEMS Microbiol Rev 2012;36:340-63.
83. Jacoby GA. AmpC ?-lactamases. Clin Microbiol Rev 2009;22:161-82.
84. Choi SH, Lee JE, Park SJ, et al. Emergence of antibiotic resistance during therapy for infections caused by Enterobacteriaceae producing AmpC ?-lactamase: Implications for antibiotic use. Antimicrob Agents Chemother 2008;52:995-1000.
85. Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing, 2014. http://ncipd.org/control/images/NCIPD-docs/CLSI-M100-S24.pdf.
86. Kamruzzaman M, Patterson JD, Shoma S, et al. Relative strengths of promoters provided by common mobile genetic elements associated with resistance gene expression in Gram-negative bacteria. Antimicrob Agents Chemother 2015;59:5088-91.
87. Muniesa M, Colomer-Lluch M, Jofre J. Potential impact of environmental bacteriophages in spreading antibiotic resistance genes. Future Microbiol 2013;8:739-51.
88. Waldor MK, Mekalanos JJ. Lysogenic conversion by a filamentous phage encoding cholera toxin. Science 1996;272:1910-4.
89. Karaolis DK, Somara S, Maneval DR Jr, et al. A bacteriophage encoding a pathogenicity island, a type-IV pilus and a phage receptor in cholera bacteria. Nature 1999;399:375-9.
90. Johnston C, Martin B, Fichant G, et al. Bacterial transformation: Distribution, shared mechanisms and divergent control. Nat Rev Microbiol 2014;12:181-96.
91. Partridge SR. Analysis of antibiotic resistance regions in Gram-negative bacteria. FEMS Microbiol Rev 2011;35:820-55.
92. Frost LS, Leplae R, Summers AO, et al. Mobile genetic elements: The agents of open source evolution. Nat Rev Microbiol 2005;3:722-32.
93. Liebert CA, Hall RM, Summers AO. Transposon Tn21, flagship of the floating genome. Microbiol Mol Biol Rev 1999;63:507-22.
94. Martínez JL. Bottlenecks in the transferability of antibiotic resistance from natural ecosystems to human bacterial pathogens. Front Microbiol 2011;2:265.
95. Wellington EMH, Boxall ABA, Cross P, et al. The role of the natural environment in the emergence of antibiotic resistance in Gram-negative bacteria. Lancet Infect Dis 2013;13:155-65.
96. Karim A, Poirel L, Nagarajan S, et al. Plasmid-mediated extendedspectrum ?-lactamase (CTX-M-3 like) from India and gene association with insertion sequence ISEcp1. FEMS Microbiol Lett 2001;201:237-41.
97. Baquero F. From pieces to patterns: Evolutionary engineering in bacterial pathogens. Nat Rev Microbiol 2004;2:510-8.
98. Walsh TR. Combinatorial genetic evolution of multiresistance. Curr Opin Microbiol 2006;9:476-82.
99. Tagg KA, Iredell JR, Partridge SR. Complete sequencing of IncI1 sequence type 2 plasmid pJIE512b indicates mobilization of blaCMY-2 from an IncA/C plasmid. Antimicrob Agents Chemother 2014;58:4949-52.
100. Weinreich DM, Delaney NF, DePristo MA, et al. Darwinian evolution can follow only very few mutational paths to fitter proteins. Science 2006;312:111-14.
101. Cantón R, Coque TM. The CTX-M ?-lactamase pandemic. Curr Opin Microbiol 2006;9:466-75.
102. Caniça MM, Lu CY, Krishnamoorthy R, et al. Molecular diversity and evolution of blaTEM genes encoding ?-lactamases resistant to clavulanic acid in clinical E coli. J Mol Evol 1997;44:57-65.
103. Martínez JL, Baquero F. Emergence and spread of antibiotic resistance: Setting a parameter space. Ups J Med Sci 2014;119:68-77.
104. Shaw KJ, Rather PN, Hare RS, et al. Molecular genetics of aminoglycoside resistance genes and familial relationships of the aminoglycosidemodifying enzymes. Microbiol Rev 1993;57:138-63.
105. Davies J, Davies D. Origins and evolution of antibiotic resistance. Microbiol Mol Biol Rev 2010;74:417-33.
106. Ginn AN, Zong Z, Wiklendt AM, et al. Limited diversity in the gene pool allows prediction of third-generation cephalosporin and aminoglycoside resistance in Escherichia coli and Klebsiella pneumoniae. Int J Antimicrob Agents 2013;42:19-26.
107. Ginn AN, Wiklendt AM, Zong Z, et al. Prediction of major antibiotic resistance in Escherichia coli and Klebsiella pneumoniae in Singapore, USA and China using a limited set of gene targets. Int J Antimicrob Agents 2014;43:563-5.
108. Partridge SR, Zong Z, Iredell JR. Recombination in IS26 and Tn2 in the evolution of multiresistance regions carrying blaCTX-M-15 on conjugative IncF plasmids from Escherichia coli. Antimicrob Agents Chemother 2011;55:4971-8.
109. Hooper DC, Jacoby GA. Mechanisms of drug resistance: Quinolone resistance. Ann N Y Acad Sci 2015;1354:12-31.
110. Espedido B, Iredell J, Thomas L, et al. Wide dissemination of a carbapenemase plasmid among gram-negative bacteria: Implications of the variable phenotype. J Clin Microbiol 2005;43:4918-19.
111. Hawkey PM, Xiong J, Ye H, et al. Occurrence of a new metallo-?-lactamase IMP-4 carried on a conjugative plasmid in Citrobacter youngae from the People's Republic of China. FEMS Microbiol Lett 2001;194:53-7.
112. Bou G, Oliver A, Martínez-Beltrán J. OXA-24, a novel class D ?-lactamase with carbapenemase activity in an Acinetobacter baumannii clinical strain. Antimicrob Agents Chemother 2000;44:1556-61.
113. Allen HK, Donato J, Wang HH, et al. Call of the wild: Antibiotic resistance genes in natural environments. Nat Rev Microbiol 2010;8:251-9.
114. Forsberg KJ, Patel S, Gibson MK, et al. Bacterial phylogeny structures soil resistomes across habitats. Nature 2014;509:612-6.
115. Salyers AA, Gupta A, Wang Y. Human intestinal bacteria as reservoirs for antibiotic resistance genes. Trends Microbiol 2004;12:412-6.
116. Norman A, Hansen LH, Sørensen SJ. Conjugative plasmids: Vessels of the communal gene pool. Phil Trans R Soc B 2009;364:2275-89.
117. Sherley M, Gordon DM, Collignon PJ. Species differences in plasmid carriage in the Enterobacteriaceae. Plasmid 2003;49:79-85.
118. Van Hal SJ, Wiklendt A, Espedido B, et al. Immediate appearance of plasmid-mediated resistance to multiple antibiotics upon antibiotic selection: An argument for systematic resistance epidemiology. J Clin Microbiol 2009;47:2325-7.
119. Garcillan-Barcia MP, Alvarado A, De La Cruz F. Identification of bacterial plasmids based on mobility and plasmid population biology. FEMS Microbiol Rev 2011;35:936-56.
120. Carattoli A, Bertini A, Villa L, et al. Identification of plasmids by PCR-based replicon typing. J Microbiol Methods 2005;63:219-28.
121. Rodríguez MM, Power P, Radice M, et al. Chromosome-encoded CTX-M-3 from Kluyvera ascorbata: A possible origin of plasmid-borne CTX-M-1-derived cefotaximases. Antimicrob Agents Chemother 2004;48:4895-7.
122. Humeniuk C, Arlet G, Gautier V, et al. ?-Lactamases of Kluyvera ascorbata, probable progenitors of some plasmid-encoded CTX-M types. Antimicrob Agents Chemother 2002;46:3045-9.
123. Cantón R, González-Alba JM, Galán JC. CTX-M enzymes: Origin and diffusion. Front Microbiol 2012;3:110.
124. Price LB, Johnson JR, Aziz M, et al. The epidemic of extended-spectrum-?-lactamase-producing Escherichia coli ST131 is driven by a single highly pathogenic subclone, H30-Rx. mBio 2013;4:e00377-13.
125. Hirai I, Fukui N, Taguchi M, et al. Detection of chromosomal blaCTX-M-15 in Escherichia coli O25b-B2-ST131 isolates from the Kinki region of Japan. Int J Antimicrob Agents 2013;42:500-6.
126. Denisuik AJ, Lagacé-Wiens PR, Pitout JD, et al. Molecular epidemiology of extended-spectrum ?-lactamase-, AmpC ?-lactamase-and carbapenemase-producing Escherichia coli and Klebsiella pneumoniae isolated from Canadian hospitals over a 5 year period: CANWARD 2007-11. J Antimicrob Chemother 2013;68(suppl 1):i57-65.
127. Johnson JR, Johnston B, Clabots C, et al. Escherichia coli sequence type ST131 as the major cause of serious multidrug-resistant E. coli infections in the United States. Clin Infect Dis 2010;51:286-94.
128. Petty NK, Ben Zakour NL, Stanton-Cook M, et al. Global dissemination of a multidrug resistant Escherichia coli clone. Proc Natl Acad Sci USA 2014;111:5694-9.
129. Marcadé G, Deschamps C, Boyd A, et al. Replicon typing of plasmids in Escherichia coli producing extended-spectrum ?-lactamases. J Antimicrob Chemother 2009;63:67-71.
130. Boyd EF, Hill CW, Rich SM, et al. Mosaic structure of plasmids from natural populations of Escherichia coli. Genetics 1996;143:1091-100.
131. Clermont O, Dhanji H, Upton M, et al. Rapid detection of the O25b-ST131 clone of Escherichia coli encompassing the CTX-M-15-producing strains. J Antimicrob Chemother 2009;64:274-7.
132. Yigit H, Queenan AM, Anderson GJ, et al. Novel carbapenem-hydrolyzing ?-lactamase, KPC-1, from a carbapenem-resistant strain of Klebsiella pneumoniae. Antimicrob Agents Chemother 2001;45:1151-61.
133. Nordmann P, Naas T, Poirel L. Global spread of carbapenemase-producing Enterobacteriaceae. Emerg Infect Dis 2011;17:1791-8.
134. Partridge SR, Ginn AN, Wiklendt AM, et al. Emergence of blaKPC carbapenemase genes in Australia. Int J Antimicrob Agents 2015;45:130-6.
135. Kitchel B, Rasheed JK, Endimiani A, et al. Genetic factors associated with elevated carbapenem resistance in KPC-producing Klebsiella pneumoniae. Antimicrob Agents Chemother 2010;54:4201-7.
136. Woodford N, Turton JF, Livermore DM. Multiresistant Gram-negative bacteria: The role of high-risk clones in the dissemination of antibiotic resistance. FEMS Microbiol Rev 2011;35:736-55.
137. Martínez-Martínez L. Extended-spectrum ?-lactamases and the permeability barrier. Clin Microbiol Infect 2008;14:82-9.
138. Peleg AY, Franklin C, Bell JM, et al. Dissemination of the metallo-?-lactamase gene blaIMP-4 among Gram-negative pathogens in a clinical setting in Australia. Clin Infect Dis 2005;41:1549-56.
139. Pournaras S, Protonotariou E, Voulgari E, et al. Clonal spread of KPC-2 carbapenemase-producing Klebsiella pneumoniae strains in Greece. J Antimicrob Chemother 2009;64:348-52.
140. Navon-Venezia S, Leavitt A, Schwaber MJ, et al. First report on a hyperepidemic clone of KPC-3-producing Klebsiella pneumoniae in Israel genetically related to a strain causing outbreaks in the United States. Antimicrob Agents Chemother 2009;53:818-20.
141. Hawser SP, Bouchillon SK, Hackel M, et al. Trending 7 years of in vitro activity of tigecycline and comparators against Gram-positive and Gram-negative pathogens from the Asia-Pacific region: Tigecycline Evaluation Surveillance Trial (TEST) 2004-2010. Int J Antimicrob Agents 2012;39:490-5.
142. Kaiser RM, Castanheira M, Jones RN, et al. Trends in Klebsiella pneumoniae carbapenemase-positive K. pneumoniae in US hospitals: Report from the 2007-2009 SENTRY antimicrobial surveillance program. Diagn Microbiol Infect Dis 2013;76:356-60.
143. Salyers AA, Amábile-Cuevas CF. Why are antibiotic resistance genes so resistant to elimination? Antimicrob Agents Chemother 1997;41:2321-5.
144. Baquero F, Martínez J-L, Cantón R. Antibiotics and antibiotic resistance in water environments. Curr Opin Biotechnol 2008;19:260-5.
145. Andersson DI, Hughes D. Microbiological effects of sublethal levels of antibiotics. Nat Rev Microbiol 2014;12:465-78.
146. Hughes D, Andersson DI. Evolutionary consequences of drug resistance: Shared principles across diverse targets and organisms. Nat Rev Genet 2015;16:459-71.
147. Rogers BA, Kennedy KJ, Sidjabat HE, et al. Prolonged carriage of resistant E coli by returned travellers: Clonality, risk factors and bacterial characteristics. Eur J Clin Microbiol Infect Dis 2012;31:2413-20.
148. Kennedy K, Collignon P. Colonisation with Escherichia coli resistant to "critically important" antibiotics: A high risk for international travellers. Eur J Clin Microbiol Infect Dis 2010;29:1501-6.
149. Kuenzli E, Jaeger VK, Frei R, et al. High colonization rates of extendedspectrum ?-lactamase (ESBL)-producing Escherichia coli in Swiss travellers to South Asia-a prospective observational multicentre cohort study looking at epidemiology, microbiology and risk factors. BMC Infect Dis 2014;14:528.
150. Titelman E, Hasan CM, Iversen A, et al. Faecal carriage of extendedspectrum ?-lactamase-producing Enterobacteriaceae is common 12 months after infection and is related to strain factors. Clin Microbiol Infect 2014;20:O508-15.
151. Baquero F. Chaos, complexity, and evolution. ASM News 2003;69:543-52.
152. Enne VI, Delsol AA, Davis GR, et al. Assessment of the fitness impacts on Escherichia coli of acquisition of antibiotic resistance genes encoded by different types of genetic element. J Antimicrob Chemother 2005;56:544-51.
153. Dahlberg C, Chao L. Amelioration of the cost of conjugative plasmid carriage in Eschericha coli K12. Genetics 2003;165:1641-9.
154. Silva RF, Mendonça SCM, Carvalho LM, et al. Pervasive sign epistasis between conjugative plasmids and drug-resistance chromosomal mutations. PLoS Genet 2011;7:e1002181.
155. Sengupta M, Austin S. Prevalence and significance of plasmid maintenance functions in the virulence plasmids of pathogenic bacteria. Infect Immun 2011;79:2502-9.
156. Yamaguchi Y, Park JH, Inouye M. Toxin-antitoxin systems in bacteria and archaea. Annu Rev Genet 2011;45:61-79.
157. San Millan A, Heilbron K, MacLean RC. Positive epistasis between co-infecting plasmids promotes plasmid survival in bacterial populations. ISME J 2014;8:601-12.
158. San Millan A, Peña-Miller R, Toll-Riera M, et al. Positive selection and compensatory adaptation interact to stabilize non-transmissible plasmids. Nat Commun 2014;5; doi:10.1038/ncomms6208.
159. Giske CG, Martinez-Martinez L, Canton R, et al. EUCAST guidelines for detection of resistance mechanisms and specific resistances of clinical and/or epidemiological importance. Version1. 2013. www.eucast.org/resistance-mechanisms.
160. Tacconelli E, Cataldo MA, Dancer SJ, et al. ESCMID guidelines for the management of the infection control measures to reduce transmission of multidrug-resistant Gram-negative bacteria in hospitalized patients. Clin Microbiol Infect 2014;20(suppl 1):1-55.
161. Centers for Disease Control and Prevention. Guidance for control of carbapenem resistant Enterobacteriaceae. CRE Toolkit 2012. www.cdc. gov/hai/organisms/cre/cre-toolkit.
162. Australian Government. National Health and Medical Research Council. Australian guidelines for the prevention and control of infection in healthcare. 2010. www.nhmrc.gov.au/guidelines-publications/cd33.
163. Livermore DM, Andrews JM, Hawkey PM, et al. Are susceptibility tests enough, or should laboratories still seek ESBLs and carbapenemases directly? J Antimicrob Chemother 2012;67:1569-77.
164. Poirel L, Schrenzel J, Cherkaoui A, et al. Molecular analysis of NDM-1-producing enterobacterial isolates from Geneva, Switzerland. J Antimicrob Chemother 2011;66:1730-3.
165. Nordmann P, Poirel L. Strategies for identification of carbapenemaseproducing Enterobacteriaceae. J Antimicrob Chemother 2013;68:487-9.
166. Maurer FP, Castelberg C, Quiblier C, et al. Evaluation of carbapenemase screening and confirmation tests with Enterobacteriaceaeand development of a practical diagnostic algorithm. J Clin Microbiol 2015;53:95-104.
167. Takiff HE, Feo O. Clinical value of whole-genome sequencing of Mycobacterium tuberculosis. Lancet Infect Dis 2015;15:1077-90.
168. Pecora ND, Li N, Allard M, et al. Genomically informed surveillance for carbapenem-resistant Enterobacteriaceaein a health care system. mBio 2015;6:e01030-15.
169. Mathers AJ, Stoesser N, Sheppard AE, et al. Klebsiella pneumoniae carbapenemase (KPC) producing K. pneumoniae at a single institution: Insights into endemicity from whole genome sequencing. Antimicrob Agents Chemother 2015;59:1656-63.
170. Martínez JL. Antibiotics and antibiotic resistance genes in natural environments. Science 2008;321:365-7.
171. Tagg KA, Ginn AN, Jiang X, et al. Distribution of acquired AmpC ?-lactamase genes in Sydney, Australia. Diagn Microbiol Infect Dis 2015;83:56-8.
172. Garcillan-Barcia MP, Ruiz del Castillo B, Alvarado A, et al. Degenerate primer MOB typing of multiresistant clinical isolates of E coli uncovers new plasmid backbones. Plasmid 2015;77:17-27.
173. Jain A, Srivastava P. Broad host range plasmids. FEMS Microbiol Lett 2013;348:87-96.
174. Guiney DG. Broad host range conjugative and mobilizable plasmids in Gram-negative bacteria. In: Clewell DB, ed. Bacterial conjugation. Plenum Press, 1993:75-103.
175. Stecher B, Denzler R, Maier L, et al. Gut inflammation can boost horizontal gene transfer between pathogenic and commensal Enterobacteriaceae. Proc Natl Acad Sci USA 2012;109:1269-74.
176. Stecher B, Maier L, Hardt WD. "Blooming" in the gut: How dysbiosis might contribute to pathogen evolution. Nat Rev Microbiol 2013;11:277-84.
177. Bartlett JG. A call to arms: The imperative for antimicrobial stewardship. Clin Infect Dis 2011;53(suppl 1):S4-7.
178. ARISE Investigators and the ANZICS Clinical Trials Group. Goal-directed resuscitation for patients with early septic shock. N Engl J Med 2014;371:1496-506.
179. Davey P, Brown E, Charani E, et al. Interventions to improve antibiotic prescribing practices for hospital inpatients. Cochrane Database Syst Rev 2013;4:CD003543.
180. Filice G, Drekonja D, Greer N, et al. Antimicrobial stewardship programs in inpatient settings: A systematic review. Department of Veterans Affairs, 2013. www.ncbi.nlm.nih.gov/books/NBK253513.
181. Butler CC, Dunstan F, Heginbothom M, et al. Containing antibiotic resistance: Decreased antibiotic-resistant coliform urinary tract infections with reduction in antibiotic prescribing by general practices. Br J Gen Pract 2007;57:785-92.
182. Hunter PA, Dawson S, French GL, et al. Antimicrobial-resistant pathogens in animals and man: Prescribing, practices and policies. J Antimicrob Chemother 2010;65(suppl 1):i3-17.
183. Laxminarayan R, Duse A, Wattal C, et al. Antibiotic resistance-the need for global solutions. Lancet Infect Dis 2013;13:1057-98.
184. Antonopoulos DA, Huse SM, Morrison HG, et al. Reproducible community dynamics of the gastrointestinal microbiota following antibiotic perturbation. Infect Immun 2009;77:2367-75.
185. Ginn AN, Wiklendt AM, Gidding HF, et al. The ecology of antibiotic use in the ICU: Homogeneous prescribing of cefepime but not tazocin selects for antibiotic resistant infection. PLoS One 2012;7:e38719.
186. Paterson DL. "Collateral damage" from cephalosporin or quinolone antibiotic therapy. Clin Infect Dis 2004;38(suppl 4):S341-5.
187. Spellberg B, Blaser M, Guidos RJ, et al. Combating antimicrobial resistance: Policy recommendations to save lives. Clin Infect Dis 2011;52(suppl 5):S397-428.
188. Read AF, Day T, Huijben S. The evolution of drug resistance and the curious orthodoxy of aggressive chemotherapy. Proc Natl Acad Sci USA 2011;108(suppl 2):10871-7.
189. Daneman N, Sarwar S, Fowler RA, et al. Effect of selective decontamination on antimicrobial resistance in intensive care units: A systematic review and meta-analysis. Lancet Infect Dis 2013;13:328-41.
190. Brener SJ, Mehran R, Brodie BR, et al. Predictors and implications of coronary infarct artery patency at initial angiography in patients with acute myocardial infarction (from the CADILLAC and HORIZONS-AMI Trials). Am J Cardiol 2011;108:918-23.
191. Cuthbertson BH, Campbell MK, MacLennan G, et al. Clinical stakeholders' opinions on the use of selective decontamination of the digestive tract in critically ill patients in intensive care units: An international Delphi study. Crit Care 2013;17:R266-6.
192. De Smet AM, Kluytmans JA, Blok HE, et al. Selective digestive tract decontamination and selective oropharyngeal decontamination and antibiotic resistance in patients in intensive-care units: An openlabel, clustered group-randomised, crossover study. Lancet Infect Dis 2011;11:372-80.
193. Vardakas KZ, Tansarli GS, Rafailidis PI, et al. Carbapenems versus alternative antibiotics for the treatment of bacteraemia due to Enterobacteriaceae producing extended-spectrum ?-lactamases: A systematic review and meta-analysis. J Antimicrob Chemother 2012;67:2793-803.
194. Sbrana F, Malacarne P, Viaggi B, et al. Carbapenem-sparing antibiotic regimens for infections caused by Klebsiella pneumoniae carbapenemaseproducing K pneumoniae in intensive care unit. Clin Infect Dis 2013;56:697-700.
195. Falagas ME, Lourida P, Poulikakos P, et al. Antibiotic treatment of infections due to carbapenem-resistant Enterobacteriaceae: Systematic evaluation of the available evidence. Antimicrob Agents Chemother 2014;58:654-63.
196. Tzouvelekis LS, Markogiannakis A, Piperaki E, et al. Treating infections caused by carbapenemase-producing Enterobacteriaceae. Clin Microbiol Infect 2014;20:862-72.
197. Ho VP, Barie PS, Stein SL, et al. Antibiotic regimen and the timing of prophylaxis are important for reducing surgical site infection after elective abdominal colorectal surgery. Surg Infect 2011;12:255-60.
198. Bulik CC, Nicolau DP. Double-carbapenem therapy for carbapenemaseproducing Klebsiella pneumoniae. Antimicrob Agents Chemother 2011;55:3002-4.
199. Giamarellou H, Galani L, Baziaka F, et al. Double-carbapenem regimen for carbapenemase-producing pandrug-resistant Klebsiella pneumoniae infections: Is it really effective in humans? Antimicrob Agents Chemother 2013;57:2388-90.
200. Oliva A, D'Abramo A, D'Agostino C, et al. Synergistic activity and effectiveness of a double-carbapenem regimen in pandrug-resistant Klebsiella pneumoniae bloodstream infections. J Antimicrob Chemother 2014; published online 11 Feb; doi:10.1093/jac/dku027.
201. Rahme C, Butterfield JM, Nicasio AM, et al. Dual beta-lactam therapy for serious Gram-negative infections: Is it time to revisit? Diagn Microbiol Infect Dis 2014;80:239-59.
202. Mainardi JL, Gutmann L, Acar JF, et al. Synergistic effect of amoxicillin and cefotaxime against Enterococcus faecalis. Antimicrob Agents Chemother 1995;39:1984-7.
203. Ling LL, Schneider T, Peoples AJ, et al. A new antibiotic kills pathogens without detectable resistance. Nature 2015;517:455-9.
204. Yang J, Hocking DM, Cheng C, et al. Disarming bacterial virulence through chemical inhibition of the DNA binding domain of an AraC-like transcriptional activator protein. J Biol Chem 2013;288:31115-26.
205. Koppolu V, Osaka I, Skredenske JM, et al. Small-molecule inhibitor of the Shigella flexneri master virulence regulator VirF. Infect Immun 2013;81:4220-31.
206. LaSarre B, Federle MJ. Exploiting quorum sensing to confuse bacterial pathogens. Microbiol Mol Biol Rev 2013;77:73-111.
207. Desroy N, Denis A, Oliveira C, et al. Novel HldE-K inhibitors leading to attenuated Gram negative bacterial virulence. J Med Chem 2013;56:1418-30.
208. Kvist M, Hancock V, Klemm P. Inactivation of efflux pumps abolishes bacterial biofilm formation. Appl Environ Microbiol 2008;74:7376-82.
209. Kern WV, Steinke P, Schumacher A, et al. Effect of 1-(1-naphthylmethyl)-piperazine, a novel putative efflux pump inhibitor, on antimicrobial drug susceptibility in clinical isolates of Escherichia coli. J Antimicrob Chemother 2006;57:339-43.
210. Schumacher A, Steinke P, Bohnert JA, et al. Effect of 1-(1-naphthylmethyl)-piperazine, a novel putative efflux pump inhibitor, on antimicrobial drug susceptibility in clinical isolates of Enterobacteriaceae other than Escherichia coli. J Antimicrob Chemother 2006;57:344-8.
211. Leitner I, Nemeth J, Feurstein T, et al. The third-generation P-glycoprotein inhibitor tariquidar may overcome bacterial multidrug resistance by increasing intracellular drug concentration. J Antimicrob Chemother 2011;66:834-9.
212. Prasad P, Sun J, Danner RL, et al. Excess deaths associated with tigecycline after approval based on noninferiority trials. Clin Infect Dis 2012;54:1699-709.
213. Devasahayam G, Scheld WM, Hoffman PS. Newer antibacterial drugs for a new century. Expert Opin Investig Drugs 2010;19:215-34.
214. Livermore DM, Warner M, Mushtaq S, et al. What remains against carbapenem-resistant Enterobacteriaceae? Evaluation of chloramphenicol, ciprofloxacin, colistin, fosfomycin, minocycline, nitrofurantoin, temocillin and tigecycline. Int J Antimicrob Agents 2011;37:415-9.
215. Lagacé-Wiens P, Walkty A, Karlowsky JA. Ceftazidime-avibactam: An evidence-based review of its pharmacology and potential use in the treatment of Gram-negative bacterial infections. Core Evid 2014;9:13-25.
216. Wang X, Zhang F, Zhao C, et al. In vitro activities of ceftazidime-avibactam and aztreonam-avibactam against 372 Gram-negative bacilli collected in 2011 and 2012 from 11 teaching hospitals in China. Antimicrob Agents Chemother 2014;58:1774-8.
217. Solomkin JS, Ramesh MK, Cesnauskas G, et al. Phase 2, randomized, double-blind study of the efficacy and safety of two dose regimens of eravacycline versus ertapenem for adult community-acquired complicated intra-abdominal infections. Antimicrob Agents Chemother 2014;58:1847-54.
218. Sutcliffe JA, O'Brien W, Fyfe C, et al. Antibacterial activity of eravacycline (TP-434), a novel fluorocycline, against hospital and community pathogens. Antimicrob Agents Chemother 2013;57:5548-58.
219. Galani I, Souli M, Daikos GL, et al. Activity of plazomicin (ACHN-490) against MDR clinical isolates of Klebsiella pneumoniae, Escherichia coli, and Enterobacter spp from Athens, Greece. J Chemother 2012;24:191-4.
220. Livermore DM, Mushtaq S, Warner M, et al. Activity of aminoglycosides, including ACHN-490, against carbapenem-resistant Enterobacteriaceaeisolates. J Antimicrob Chemother 2011;66:48-53.
221. Drawz S, Papp-Wallace K, Bonomo R. New ?-lactamase inhibitors: A therapeutic renaissance in an MDR world. Antimicrob Agents Chemother 2014;58:1835-46.
222. Pucci MJ, Bush K. Investigational antimicrobial agents of 2013. Clin Microbiol Rev 2013;26:792-821.
223. Mandal SM, Roy A, Ghosh AK, et al. Challenges and future prospects of antibiotic therapy: From peptides to phages utilization. Front Pharmacol 2014;5:105.
224. Li W, Tailhades J, O'Brien-Simpson N, et al. Proline-rich antimicrobial peptides: Potential therapeutics against antibiotic-resistant bacteria. Amino Acids 2014;46:2287-94.
225. Feng Q, Huang Y, Chen M, et al. Functional synergy of ?-helical antimicrobial peptides and traditional antibiotics against Gram-negative and Gram-positive bacteria in vitro and in vivo. Eur J Clin Microbiol Infect Dis 2015;34:197-204.
226. Gruenheid S, Le Moual H. Resistance to antimicrobial peptides in Gramnegative bacteria. FEMS Microbiol Lett 2012;330:81-9.
227. Rao GG, Ly NS, Haas CE, et al. New dosing strategies for an "old" antibiotic: Pharmacodynamics of front-loaded regimens of colistin at simulated pharmacokinetics of patients with kidney or liver disease. Antimicrob Agents Chemother 2014;58:1381-8.
228. Nation RL, Li J. Colistin in the 21st century. Curr Opin Infect Dis 2009;22:535.
229. Neonakis IK, Samonis G, Messaritakis H, et al. Resistance status and evolution trends of Klebsiella pneumoniae isolates in a university hospital in Greece: Ineffectiveness of carbapenems and increasing resistance to colistin. Chemotherapy 2010;56:448-52.
230. Vaara M. Novel derivatives of polymyxins. J Antimicrob Chemother 2013;68:1213-9.
231. 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 Resist 2012;18:132-6.
232. Liu YY, Wang Y, Walsh TR, et al. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: A microbiological and molecular biological study. Lancet Infect Dis 2015; published online 18 Nov; doi:10.1016/S1473-3099(15)00424-7.
233. Karageorgopoulos DE, Miriagou V, Tzouvelekis LS, et al. Emergence of resistance to fosfomycin used as adjunct therapy in KPC Klebsiella pneumoniae bacteraemia: Report of three cases. J Antimicrob Chemother 2012;67:2777-9.
234. Falagas ME, Kastoris AC, Kapaskelis AM, et al. Fosfomycin for the treatment of multidrug-resistant, including extended-spectrum ?-lactamase producing, Enterobacteriaceae infections: A systematic review. Lancet Infect Dis 2010;10:43-50.
235. Michalopoulos AS, Livaditis IG, Gougoutas V. The revival of fosfomycin. Int J Infect Dis 2011;15:e732-9.
236. Pontikis K, Karaiskos I, Bastani S, et al. Outcomes of critically ill intensive care unit patients treated with fosfomycin for infections due to pandrugresistant and extensively drug-resistant carbapenemase-producing Gramnegative bacteria. Int J Antimicrob Agents 2014;43:52-9.
237. Twort FW. The ultra-microscopic viruses. Lancet 1921;198:204.
238. Twort FW. An investigation on the nature of ultra-microscopic viruses. Lancet 1915;186:1241-3.
239. Hérelle F. Sur un microbe invisible antagoniste des bacilles dysentériques. C R Acad Sci Ser D Paris 1917:373-5.
240. Stone R. Bacteriophage therapy. Stalin's forgotten cure. Science 2002;298:728-31.
241. Ly-Chatain MH. The factors affecting effectiveness of treatment in phages therapy. Front Microbiol 2014;5:51.
242. Khawaldeh A, Morales S, Dillon B, et al. Bacteriophage therapy for refractory Pseudomonas aeruginosa urinary tract infection. J Med Microbiol 2011;60(pt 11):1697-700.
243. Burrowes B, Harper DR, Anderson J, et al. Bacteriophage therapy: Potential uses in the control of antibiotic-resistant pathogens. Expert Rev Anti Infect Ther 2011;9:775-85.
244. Bragg R, Van Der Westhuizen W, Lee JY, et al. Bacteriophages as potential treatment option for antibiotic resistant bacteria. Adv Exp Med Biol 2014;807:97-110.
245. Barrangou R, Marraffini Luciano A. CRISPR-Cas systems: Prokaryotes upgrade to adaptive immunity. Mol Cell 2014;54:234-44.
246. Gomaa AA, Klumpe HE, Luo ML, et al. Programmable removal of bacterial strains by use of genome-targeting CRISPR-Cas systems. mBio 2014;5:e00928-13.
247. Citorik RJ, Mimee M, Lu TK. Sequence-specific antimicrobials using efficiently delivered RNA-guided nucleases. Nat Biotech 2014;32:1141-5.
248. Van Der Waaij D, Berghuis JM. Determination of the colonization resistance of the digestive tract of individual mice. J Hyg 1974;72:379-87.
249. Wilson KH, Silva J, Fekety FR. Suppression of Clostridium difficile by normal hamster cecal flora and prevention of antibiotic-associated cecitis. Infect Immun 1981;34:626-8.
250. Heidt PJ, Van Der Waaij D, Vossen JM, et al. The use of a human donor flora for recontamination following antibiotic decontamination. Prog Food Nutr Sci 1983;7:53-63.
251. Tvede M, Rask-Madsen J. Bacteriotherapy for chronic relapsing Clostridium difficile diarrhoea in six patients. Lancet 1989;1:1156-60.
252. Youngster I, Sauk J, Pindar C, et al. Fecal microbiota transplant for relapsing Clostridium difficile infection using a frozen inoculum from unrelated donors: A randomized, open-label, controlled pilot study. Clin Infect Dis 2014;58:1515-22.
253. Ananthakrishnan AN. Clostridium difficile infection: Epidemiology, risk factors and management. Nat Rev Gastroenterol Hepatol 2011;8:17-26.
254. Kachrimanidou M, Malisiovas N. Clostridium difficile infection: A comprehensive review. Crit Rev Microbiol 2011;37:178-87.
255. Yurist-Doutsch S, Arrieta MC, Vogt SL, et al. Gastrointestinal microbiotamediated control of enteric pathogens. Annu Rev Genet 2014;10:10.
256. Petschow B, Dore J, Hibberd P, et al. Probiotics, prebiotics, and the host microbiome: The science of translation. Ann N Y Acad Sci 2013:1306:1-17.
257. Ley RE. Harnessing microbiota to kill a pathogen: The sweet tooth of Clostridium difficile. Nat Med 2014;20:248-9.
258. Ng KM, Ferreyra JA, Higginbottom SK, et al. Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens. Nature 2013;502:96-9.
259. Lawley TD, Clare S, Walker AW, et al. Targeted restoration of the intestinal microbiota with a simple, defined bacteriotherapy resolves relapsing Clostridium difficile disease in mice. PLoS Pathog 2012;8:25.
260. Gillings MR, Paulsen IT, Tetu SG. Ecology and evolution of the human microbiota: FiRe, FaRmInG AnD AnTiBiOtIcS. GEnEs (BaSeL) 2015;6:841-57.