1887
No metrics data to plot.
The attempt to load metrics for this article has failed.
The attempt to plot a graph for these metrics has failed.

EcoSal Plus

Domain 11: Antibiotic Mechanisms and Resistance

Aminoglycoside Revival: Review of a Historically Important Class of Antimicrobials Undergoing Rejuvenation

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.
  • XML
    155.56 Kb
  • PDF
    1.88 MB
  • HTML
    167.59 Kb
  • Authors: Alisa W. Serio1, Tiffany Keepers2, Logan Andrews3, and Kevin M. Krause4
  • Editor: Karen Bush5
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Achaogen Inc., South San Francisco, CA 94080; 2: Achaogen Inc., South San Francisco, CA 94080; 3: Achaogen Inc., South San Francisco, CA 94080; 4: Achaogen Inc., South San Francisco, CA 94080; 5: Department of Biology, Indiana University, Bloomington, IN
  • Received 25 January 2018 Accepted 25 September 2018 Published 16 November 2018
  • Address correspondence to Alisa W. Serio, [email protected]
image of Aminoglycoside Revival: Review of a Historically Important Class of Antimicrobials Undergoing Rejuvenation
    Preview this reference work article:
    Zoom in
    Zoomout

    Aminoglycoside Revival: Review of a Historically Important Class of Antimicrobials Undergoing Rejuvenation, Page 1 of 2

    | /docserver/preview/fulltext/ecosalplus/8/1/ESP-0002-2018-1.gif /docserver/preview/fulltext/ecosalplus/8/1/ESP-0002-2018-2.gif
  • Abstract:

    Aminoglycosides are cidal inhibitors of bacterial protein synthesis that have been utilized for the treatment of serious bacterial infections for almost 80 years. There have been approximately 15 members of this class approved worldwide for the treatment of a variety of infections, many serious and life threatening. While aminoglycoside use declined due to the introduction of other antibiotic classes such as cephalosporins, fluoroquinolones, and carbapenems, there has been a resurgence of interest in the class as multidrug-resistant pathogens have spread globally. Furthermore, aminoglycosides are recommended as part of combination therapy for empiric treatment of certain difficult-to-treat infections. The development of semisynthetic aminoglycosides designed to overcome common aminoglycoside resistance mechanisms, and the shift to once-daily dosing, has spurred renewed interest in the class. Plazomicin is the first new aminoglycoside to be approved by the FDA in nearly 40 years, marking the successful start of a new campaign to rejuvenate the class.

  • Citation: Serio A, Keepers T, Andrews L, Krause K. 2018. Aminoglycoside Revival: Review of a Historically Important Class of Antimicrobials Undergoing Rejuvenation, EcoSal Plus 2018; doi:10.1128/ecosalplus.ESP-0002-2018

References

1. Kresge N, Simoni RD, Hill RL. 2004. Selman Waksman: the father of antibiotics. J Biol Chem 279:e7.
2. Woodruff HB, Selman A. 2014. Selman A. Waksman, winner of the 1952 Nobel Prize for physiology or medicine. Appl Environ Microbiol 80:2–8. [PubMed]
3. Ristuccia AM, Cunha BA. 1985. An overview of amikacin. Ther Drug Monit 7:12–25.
4. Aggen JB, Armstrong ES, Goldblum AA, Dozzo P, Linsell MS, Gliedt MJ, Hildebrandt DJ, Feeney LA, Kubo A, Matias RD, Lopez S, Gomez M, Wlasichuk KB, Diokno R, Miller GH, Moser HE. 2010. Synthesis and spectrum of the neoglycoside ACHN-490. Antimicrob Agents Chemother 54:4636–4642. [PubMed]
5. Landman D, Babu E, Shah N, Kelly P, Bäcker M, Bratu S, Quale J. 2010. Activity of a novel aminoglycoside, ACHN-490, against clinical isolates of Escherichia coli and Klebsiella pneumoniae from New York City. J Antimicrob Chemother 65:2123–2127. [PubMed]
6. Sorlozano A, Jimenez-Pacheco A, de Dios Luna Del Castillo J, Sampedro A, Martinez-Brocal A, Miranda-Casas C, Navarro-Marí JM, Gutiérrez-Fernández J. 2014. Evolution of the resistance to antibiotics of bacteria involved in urinary tract infections: a 7-year surveillance study. Am J Infect Control 42:1033–1038. [PubMed]
7. Sader HS, Rhomberg PR, Farrell DJ, Jones RN. 2015. Arbekacin activity against contemporary clinical bacteria isolated from patients hospitalized with pneumonia. Antimicrob Agents Chemother 59:3263–3270. [PubMed]
8. Landman D, Kelly P, Bäcker M, Babu E, Shah N, Bratu S, Quale J. 2011. Antimicrobial activity of a novel aminoglycoside, ACHN-490, against Acinetobacter baumannii and Pseudomonas aeruginosa from New York City. J Antimicrob Chemother 66:332–334. [PubMed]
9. Heine HS, Hershfield J, Marchand C, Miller L, Halasohoris S, Purcell BK, Worsham PL. 2015. In vitro antibiotic susceptibilities of Yersinia pestis determined by broth microdilution following CLSI methods. Antimicrob Agents Chemother 59:1919–1921. [PubMed]
10. Mega WM, Doyle-Eisele M, Cass RT, Kostrub CF, Sherwood RL, Metz MA, Cirz RT. 2016. Plazomicin is effective in a non-human primate pneumonic plague model. Bioorg Med Chem 24:6429–6439. [PubMed]
11. Kreizinger Z, Makrai L, Helyes G, Magyar T, Erdélyi K, Gyuranecz M. 2013. Antimicrobial susceptibility of Francisella tularensis subsp. holarctica strains from Hungary, Central Europe. J Antimicrob Chemother 68:370–373. [PubMed]
12. Kiliç S, Celebi B, Acar B, Ataş M. 2013. In vitro susceptibility of isolates of Francisella tularensis from Turkey. Scand J Infect Dis 45:337–341. [PubMed]
13. Gonzalo X, Casali N, Broda A, Pardieu C, Drobniewski F. 2015. Combination of amikacin and doxycycline against multidrug-resistant and extensively drug-resistant tuberculosis. Int J Antimicrob Agents 45:406–412. [PubMed]
14. Ji B, Lefrançois S, Robert J, Chauffour A, Truffot C, Jarlier V. 2006. In vitro and in vivo activities of rifampin, streptomycin, amikacin, moxifloxacin, R207910, linezolid, and PA-824 against Mycobacterium ulcerans. Antimicrob Agents Chemother 50:1921–1926. [PubMed]
15. Xie J, Talaska AE, Schacht J. 2011. New developments in aminoglycoside therapy and ototoxicity. Hear Res 281:28–37. [PubMed]
16. Avent ML, Rogers BA, Cheng AC, Paterson DL. 2011. Current use of aminoglycosides: indications, pharmacokinetics and monitoring for toxicity. Intern Med J 41:441–449. [PubMed]
17. Simonsen KA, Anderson-Berry AL, Delair SF, Davies HD. 2014. Early-onset neonatal sepsis. Clin Microbiol Rev 27:21–47. [PubMed]
18. Boulanger LL, Ettestad P, Fogarty JD, Dennis DT, Romig D, Mertz G. 2004. Gentamicin and tetracyclines for the treatment of human plague: review of 75 cases in New Mexico, 1985-1999. Clin Infect Dis 38:663–669. [PubMed]
19. Inglesby TV, Dennis DT, Henderson DA, Bartlett JG, Ascher MS, Eitzen E, Fine AD, Friedlander AM, Hauer J, Koerner JF, Layton M, McDade J, Osterholm MT, O’Toole T, Parker G, Perl TM, Russell PK, Schoch-Spana M, Tonat K, Working Group on Civilian Biodefense. 2000. Plague as a biological weapon: medical and public health management. JAMA 283:2281–2290. [PubMed]
20. Hepburn MJ, Simpson AJ. 2008. Tularemia: current diagnosis and treatment options. Expert Rev Anti Infect Ther 6:231–240. [PubMed]
21. Grill MF, Maganti RK. 2011. Neurotoxic effects associated with antibiotic use: management considerations. Br J Clin Pharmacol 72:381–393. [PubMed]
22. Vandewalle A, Farman N, Morin JP, Fillastre JP, Hatt PY, Bonvalet JP, Gastineau M, Wanstok F. 1981. Gentamicin incorporation along the nephron: autoradiographic study on isolated tubules. Kidney Int 19:529–539. [PubMed]
23. Dai CF, Mangiardi D, Cotanche DA, Steyger PS. 2006. Uptake of fluorescent gentamicin by vertebrate sensory cells in vivo. Hear Res 213:64–78. [PubMed]
24. Jiang M, Karasawa T, Steyger PS. 2017. Aminoglycoside-induced cochleotoxicity: a review. Front Cell Neurosci 11:308. doi:10.3389/fncel.2017.00308. [PubMed]
25. Lopez-Novoa JM, Quiros Y, Vicente L, Morales AI, Lopez-Hernandez FJ. 2011. New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view. Kidney Int 79:33–45. [PubMed]
26. Meyer RD. 1986. Risk factors and comparisons of clinical nephrotoxicity of aminoglycosides. Am J Med 80(6B) :119–125.
27. Mingeot-Leclercq MP, Tulkens PM. 1999. Aminoglycosides: nephrotoxicity. Antimicrob Agents Chemother 43:1003–1012. [PubMed]
28. Nagai J, Takano M. 2014. Entry of aminoglycosides into renal tubular epithelial cells via endocytosis-dependent and endocytosis-independent pathways. Biochem Pharmacol 90:331–337. [PubMed]
29. Fabre J, Rudhardt M, Blanchard P, Regamey C. 1976. Persistence of sisomicin and gentamicin in renal cortex and medulla compared with other organs and serum of rats. Kidney Int 10:444–449. [PubMed]
30. Sandoval R, Leiser J, Molitoris BA. 1998. Aminoglycoside antibiotics traffic to the Golgi complex in LLC-PK1 cells. J Am Soc Nephrol 9:167–174. [PubMed]
31. Garinis AC, Cross CP, Srikanth P, Carroll K, Feeney MP, Keefe DH, Hunter LL, Putterman DB, Cohen DM, Gold JA, Steyger PS. 2017. The cumulative effects of intravenous antibiotic treatments on hearing in patients with cystic fibrosis. J Cyst Fibros 16:401–409. [PubMed]
32. Ariano RE, Zelenitsky SA, Kassum DA. 2008. Aminoglycoside-induced vestibular injury: maintaining a sense of balance. Ann Pharmacother 42:1282–1289. [PubMed]
33. O’Sullivan ME, Perez A, Lin R, Sajjadi A, Ricci AJ, Cheng AG. 2017. Towards the prevention of aminoglycoside-related hearing loss. Front Cell Neurosci 11:325. doi:10.3389/fncel.2017.00325. [PubMed]
34. Wong J, Brown G. 1996. Does once-daily dosing of aminoglycosides affect neuromuscular function? J Clin Pharm Ther 21:407–411. [PubMed]
35. Barrons RW. 1997. Drug-induced neuromuscular blockade and myasthenia gravis. Pharmacotherapy 17:1220–1232. [PubMed]
36. Soloviev VN, Firsov AA, Dolgova GV, Berezhinskaya VV, Fishman VM. 1977. Relationship between the neuromuscular blocking effect of gentamicin and streptomycin and their concentration in blood. Acta Biol Med Ger 36:1307–1314. [PubMed]
37. Lee SI, Lee JH, Lee SC, Lee JM, Lee JH. 2008. Calcium and neostigmine antagonize gentamicin, but augment clindamycin-induced tetanic fade in rat phrenic nerve-hemidiaphragm preparations. J Anesth 22:385–390. [PubMed]
38. Paradelis AG, Triantaphyllidis CJ, Mironidou M, Crassaris LG, Karachalios DN, Giala MM. 1988. Interaction of aminoglycoside antibiotics and calcium channel blockers at the neuromuscular junctions. Methods Find Exp Clin Pharmacol 10:687–690. [PubMed]
39. Le J, McKee B, Srisupha-Olarn W, Burgess DS. 2011. In vitro activity of carbapenems alone and in combination with amikacin against KPC-producing Klebsiella pneumoniae. J Clin Med Res 3:106–110.
40. Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, et al. 2017. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Crit Care Med 45:486–552. [PubMed]
41. Tamma PD, Cosgrove SE, Maragakis LL. 2012. Combination therapy for treatment of infections with gram-negative bacteria. Clin Microbiol Rev 25:450–470. [PubMed]
42. Sick AC, Tschudin-Sutter S, Turnbull AE, Weissman SJ, Tamma PD. 2014. Empiric combination therapy for gram-negative bacteremia. Pediatrics 133:e1148–e1155. [PubMed]
43. May AK. 2016. An argument for the use of aminoglycosides in the empiric treatment of ventilator-associated pneumonia. Surg Infect (Larchmt) 17:329–333. [PubMed]
44. Nicolau DP, Belliveau PP, Nightingale CH, Quintiliani R, Freeman CD. 1995. Implementation of a once-daily aminoglycoside program in a large community-teaching hospital. Hosp Pharm 30:674–676, 679–680. [PubMed]
45. Drusano GL, Ambrose PG, Bhavnani SM, Bertino JS, Nafziger AN, Louie A. 2007. Back to the future: using aminoglycosides again and how to dose them optimally. Clin Infect Dis 45:753–760. [PubMed]
46. Stankowicz MS, Ibrahim J, Brown DL. 2015. Once-daily aminoglycoside dosing: an update on current literature. Am J Health Syst Pharm 72:1357–1364. [PubMed]
47. De Waele JJ, De Neve N. 2014. Aminoglycosides for life-threatening infections: a plea for an individualized approach using intensive therapeutic drug monitoring. Minerva Anestesiol 80:1135–1142. [PubMed]
48. Davis BD. 1987. Mechanism of bactericidal action of aminoglycosides. Microbiol Rev 51:341–350. [PubMed]
49. Mingeot-Leclercq MP, Glupczynski Y, Tulkens PM. 1999. Aminoglycosides: activity and resistance. Antimicrob Agents Chemother 43:727–737. [PubMed]
50. Taber HW, Mueller JP, Miller PF, Arrow AS. 1987. Bacterial uptake of aminoglycoside antibiotics. Microbiol Rev 51:439–457. [PubMed]
51. Anand N, Davis BD. 1960. Damage by streptomycin to the cell membrane of Escherichia coli. Nature 185:22–23. [PubMed]
52. Anand N, Davis BD, Armitage AK. 1960. Uptake of streptomycin by Escherichia coli. Nature 185:23–24. [PubMed]
53. Bryan LE, Van Den Elzen HM. 1977. Effects of membrane-energy mutations and cations on streptomycin and gentamicin accumulation by bacteria: a model for entry of streptomycin and gentamicin in susceptible and resistant bacteria. Antimicrob Agents Chemother 12:163–177.
54. Bryan LE, Van den Elzen HM. 1976. Streptomycin accumulation in susceptible and resistant strains of Escherichia coli and Pseudomonas aeruginosa. Antimicrob Agents Chemother 9:928–938.
55. Stratton C. 2005. Molecular mechanisms of action for antimicrobial agents: general principles and mechanisms for selected classes of antibiotics, p 532–563. In Lorian V (ed). Antibiotics in Laboratory Medicine, 5th ed. Lippincott Williams & Wilkins, Philadelphia, PA.
56. Ramirez MS, Tolmasky ME. 2010. Aminoglycoside modifying enzymes. Drug Resist Updat 13:151–171. [PubMed]
57. Schlessinger D. 1988. Failure of aminoglycoside antibiotics to kill anaerobic, low-pH, and resistant cultures. Clin Microbiol Rev 1:54–59. [PubMed]
58. Jana S, Deb JK. 2006. Molecular understanding of aminoglycoside action and resistance. Appl Microbiol Biotechnol 70:140–150. [PubMed]
59. Martin WJ, Gardner M, Washington JA II. 1972. In vitro antimicrobial susceptibility of anaerobic bacteria isolated from clinical specimens. Antimicrob Agents Chemother 1:148–158. [PubMed]
60. Kislak JW. 1972. The susceptibility of Bacteroides fragilis to 24 antibiotics. J Infect Dis 125:295–299. [PubMed]
61. Nichols WW, Young SN. 1985. Respiration-dependent uptake of dihydrostreptomycin by Escherichia coli. Its irreversible nature and lack of evidence for a uniport process. Biochem J 228:505–512. [PubMed]
62. Davis BD, Chen LL, Tai PC. 1986. Misread protein creates membrane channels: an essential step in the bactericidal action of aminoglycosides. Proc Natl Acad Sci USA 83:6164–6168. [PubMed]
63. Yoshimura F, Nikaido H. 1985. Diffusion of beta-lactam antibiotics through the porin channels of Escherichia coli K-12. Antimicrob Agents Chemother 27:84–92. [PubMed]
64. Harder KJ, Nikaido H, Matsuhashi M. 1981. Mutants of Escherichia coli that are resistant to certain beta-lactam compounds lack the ompF porin. Antimicrob Agents Chemother 20:549–552. [PubMed]
65. Hirai K, Aoyama H, Irikura T, Iyobe S, Mitsuhashi S. 1986. Differences in susceptibility to quinolones of outer membrane mutants of Salmonella typhimurium and Escherichia coli. Antimicrob Agents Chemother 29:535–538. [PubMed]
66. Thanassi DG, Suh GS, Nikaido H. 1995. Role of outer membrane barrier in efflux-mediated tetracycline resistance of Escherichia coli. J Bacteriol 177:998–1007. [PubMed]
67. Delcour AH. 2009. Outer membrane permeability and antibiotic resistance. Biochim Biophys Acta 1794:808–816. [PubMed]
68. Pagès JM, James CE, Winterhalter M. 2008. The porin and the permeating antibiotic: a selective diffusion barrier in Gram-negative bacteria. Nat Rev Microbiol 6:893–903. [PubMed]
69. Fei Y, Ma V, Maerkl N, You P. 2012. The down regulation of E. coli OmpF in response to sub-inhibitory concentrations of kanamycin is not mediated by MarA. J ExpMicrobiol Immunol 16:101–107.
70. Foulds J, Chai TJ. 1978. New major outer membrane proteins found in an Escherichia coli tolF mutant resistant to bacteriophage TuIb. J Bacteriol 133:1478–1483. [PubMed]
71. Nakae R, Nakae T. 1982. Diffusion of aminoglycoside antibiotics across the outer membrane of Escherichia coli. Antimicrob Agents Chemother 22:554–559. [PubMed]
72. Laursen BS, Sørensen HP, Mortensen KK, Sperling-Petersen HU. 2005. Initiation of protein synthesis in bacteria. Microbiol Mol Biol Rev 69:101–123. [PubMed]
73. Lodish H, Berk A, Zipursky AL, Matsudaira P, Baltimore D, Darnell J. 2000. Molecular Cell Biology, 4th ed. W. H. Freeman, New York, NY.
74. Green R, Noller HF. 1997. Ribosomes and translation. Annu Rev Biochem 66:679–716. [PubMed]
75. Kotra LP, Haddad J, Mobashery S. 2000. Aminoglycosides: perspectives on mechanisms of action and resistance and strategies to counter resistance. Antimicrob Agents Chemother 44:3249–3256. [PubMed]
76. Fourmy D, Recht MI, Blanchard SC, Puglisi JD. 1996. Structure of the A site of Escherichia coli 16S ribosomal RNA complexed with an aminoglycoside antibiotic. Science 274:1367–1371. [PubMed]
77. Fourmy D, Yoshizawa S, Puglisi JD. 1998. Paromomycin binding induces a local conformational change in the A-site of 16 S rRNA. J Mol Biol 277:333–345. [PubMed]
78. Carter AP, Clemons WM, Brodersen DE, Morgan-Warren RJ, Wimberly BT, Ramakrishnan V. 2000. Functional insights from the structure of the 30S ribosomal subunit and its interactions with antibiotics. Nature 407:340–348. [PubMed]
79. Davies J, Anderson P, Davis BD. 1965. Inhibition of protein synthesis by spectinomycin. Science 149:1096–1098. [PubMed]
80. Wilson DN. 2014. Ribosome-targeting antibiotics and mechanisms of bacterial resistance. Nat Rev Microbiol 12:35–48. [PubMed]
81. Mehta R, Champney WS. 2002. 30S ribosomal subunit assembly is a target for inhibition by aminoglycosides in Escherichia coli. Antimicrob Agents Chemother 46:1546–1549. [PubMed]
82. Wallace BJ, Tai PC, Herzog EL, Davis BD. 1973. Partial inhibition of polysomal ribosomes of Escherichia coli by streptomycin. Proc Natl Acad Sci USA 70:1234–1237. [PubMed]
83. Tai PC, Wallace BJ, Davis BD. 1973. Actions of aurintricarboxylate, kasugamycin, and pactamycin on Escherichia coli polysomes. Biochemistry 12:616–620. [PubMed]
84. Roth H, Amos H, Davis BD. 1960. Purine nucleotide excretion by Escherichia coli in the presence of streptomycin. Biochim Biophys Acta 37:398–405.
85. Tai PC, Wallace BJ, Davis BD. 1978. Streptomycin causes misreading of natural messenger by interacting with ribosomes after initiation. Proc Natl Acad Sci USA 75:275–279. [PubMed]
86. Magnet S, Blanchard JS. 2005. Molecular insights into aminoglycoside action and resistance. Chem Rev 105:477–498. [PubMed]
87. Doi Y, Wachino JI, Arakawa Y. 2016. Aminoglycoside resistance: the emergence of acquired 16S ribosomal RNA methyltransferases. Infect Dis Clin North Am 30:523–537. [PubMed]
88. Rather PN, Orosz E, Shaw KJ, Hare R, Miller G. 1993. Characterization and transcriptional regulation of the 2′-N-acetyltransferase gene from Providencia stuartii. J Bacteriol 175:6492–6498. [PubMed]
89. Cundliffe E. 1989. How antibiotic-producing organisms avoid suicide. Annu Rev Microbiol 43:207–233. [PubMed]
90. Rather PN. 1998. Origins of the aminoglycoside modifying enzymes. Drug Resist Updat 1:285–291.
91. Beauclerk AA, Cundliffe E. 1987. Sites of action of two ribosomal RNA methylases responsible for resistance to aminoglycosides. J Mol Biol 193:661–671.
92. Garneau-Tsodikova S, Labby KJ. 2016. Mechanisms of resistance to aminoglycoside antibiotics: overview and perspectives. MedChemComm 7:11–27. [PubMed]
93. Kim JY, Park YJ, Kwon HJ, Han K, Kang MW, Woo GJ. 2008. Occurrence and mechanisms of amikacin resistance and its association with beta-lactamases in Pseudomonas aeruginosa: a Korean nationwide study. J Antimicrob Chemother 62:479–483. [PubMed]
94. Castanheira M, Deshpande L, Hubler C, Mendes R, Serio A, Krause K, Flamm R. 2017. Activity of plazomicin against Enterobacteriaceae isolates collected in the United States including isolates carrying aminoglycoside-modifying enzymes detected by whole genome sequencing, abstr. 1235. IDWeek 2017, San Diego, CA, 4 to 8 October, 2017.
95. López Díaz M, Ríos E, Rodríguez-Avial I, Simaluiza RJ, Picazo JJ, Culebras E. 2017. In-vitro activity of several antimicrobial agents against methicillin-resistant Staphylococcus aureus (MRSA) isolates expressing aminoglycoside-modifying enzymes: potency of plazomicin alone and in combination with other agents. Int J Antimicrob Agents 50:191–196. [PubMed]
96. Matsumoto T. 2014. Arbekacin: another novel agent for treating infections due to methicillin-resistant Staphylococcus aureus and multidrug-resistant Gram-negative pathogens. Clin Pharmacol 6:139–148.
97. Kondo S, Hotta K. 1999. Semisynthetic aminoglycoside antibiotics: development and enzymatic modifications. J Infect Chemother 5:1–9. [PubMed]
98. Cox G, Ejim L, Stogios PJ, Koteva K, Bordeleau E, Evdokimova E, Sieron AO, Savchenko A, Serio AW, Krause KM, Wright GD. 2018. Plazomicin retains antibiotic activity against most aminoglycoside modifying enzymes. ACS Infect Dis 4:980–987. [PubMed]
99. Ramirez MS, Nikolaidis N, Tolmasky ME. 2013. Rise and dissemination of aminoglycoside resistance: the aac(6′)-Ib paradigm. Front Microbiol 4:121. doi:10.3389/fmicb.2013.00121. [PubMed]
100. Robicsek A, Strahilevitz J, Jacoby GA, Macielag M, Abbanat D, Park CH, Bush K, Hooper DC. 2006. Fluoroquinolone-modifying enzyme: a new adaptation of a common aminoglycoside acetyltransferase. Nat Med 12:83–88. [PubMed]
101. Castanheira M, Doyle T, Woosley L, Serio A, Krause K, Flamm R. 2017. Plazomicin activity against European Enterobacteriaceae isolates carrying aminoglycoside-modifying enzymes and 16S rRNA methylases, abstr. 3611. ECCMID, Vienna, Austria, 22 to 25 April 2017.
102. Castanheira M, Woosley L, Doyle T, Serio A, Krause K, Flamm R. 2017. Aminoglycoside-resistance genes among 2014-2015 US carbapenem-resistant enterobacteriaceae isolates and activity of plazomicin against characterized isolates. ASM Microbe 2017, New Orleans, LA, 1 to 5 June 2017.
103. Almaghrabi R, Clancy CJ, Doi Y, Hao B, Chen L, Shields RK, Press EG, Iovine NM, Townsend BM, Wagener MM, Kreiswirth B, Nguyen MH. 2014. Carbapenem-resistant Klebsiella pneumoniae strains exhibit diversity in aminoglycoside-modifying enzymes, which exert differing effects on plazomicin and other agents. Antimicrob Agents Chemother 58:4443–4451. [PubMed]
104. Holbrook SYL, Garneau-Tsodikova S. 2017. Evaluation of aminoglycoside and carbapenem resistance in a collection of drug-resistant Pseudomonas aeruginosa clinical isolates. Microb Drug Resist 24:1020–1030. [PubMed]
105. Aghazadeh M, Rezaee MA, Nahaei MR, Mahdian R, Pajand O, Saffari F, Hassan M, Hojabri Z. 2013. Dissemination of aminoglycoside-modifying enzymes and 16S rRNA methylases among Acinetobacter baumannii and Pseudomonas aeruginosa isolates. Microb Drug Resist 19:282–288. [PubMed]
106. Liu Z, Ling B, Zhou L. 2015. Prevalence of 16S rRNA methylase, modifying enzyme, and extended-spectrum beta-lactamase genes among Acinetobacter baumannii isolates. J Chemother 27:207–212. [PubMed]
107. Miró E, Grünbaum F, Gómez L, Rivera A, Mirelis B, Coll P, Navarro F. 2013. Characterization of aminoglycoside-modifying enzymes in enterobacteriaceae clinical strains and characterization of the plasmids implicated in their diffusion. Microb Drug Resist 19:94–99. [PubMed]
108. Tsai SF, Zervos MJ, Clewell DB, Donabedian SM, Sahm DF, Chow JW. 1998. A new high-level gentamicin resistance gene, aph(2′)-Id, in Enterococcus spp. Antimicrob Agents Chemother 42:1229–1232. [PubMed]
109. Perumal N, Murugesan S, Krishnan P. 2016. Distribution of genes encoding aminoglycoside-modifying enzymes among clinical isolates of methicillin-resistant staphylococci. Indian J Med Microbiol 34:350–352. [PubMed]
110. Mahdiyoun SM, Kazemian H, Ahanjan M, Houri H, Goudarzi M. 2016. Frequency of aminoglycoside-resistance genes in methicillin-resistant Staphylococcus aureus (MRSA) isolates from hospitalized patients. Jundishapur J Microbiol 9:e35052. doi:10.5812/jjm.35052. [PubMed]
111. Wright GD. 1999. Aminoglycoside-modifying enzymes. Curr Opin Microbiol 2:499–503.
112. Wachino J, Arakawa Y. 2012. Exogenously acquired 16S rRNA methyltransferases found in aminoglycoside-resistant pathogenic Gram-negative bacteria: an update. Drug Resist Updat 15:133–148. [PubMed]
113. Livermore DM, Mushtaq S, Warner M, Zhang JC, Maharjan S, Doumith M, Woodford N. 2011. Activity of aminoglycosides, including ACHN-490, against carbapenem-resistant Enterobacteriaceae isolates. J Antimicrob Chemother 66:48–53. [PubMed]
114. Thompson J, Skeggs PA, Cundliffe E. 1985. Methylation of 16S ribosomal RNA and resistance to the aminoglycoside antibiotics gentamicin and kanamycin determined by DNA from the gentamicin-producer, Micromonospora purpurea. Mol Gen Genet 201:168–173. [PubMed]
115. Skeggs PA, Thompson J, Cundliffe E. 1985. Methylation of 16S ribosomal RNA and resistance to aminoglycoside antibiotics in clones of Streptomyces lividans carrying DNA from Streptomyces tenjimariensis. Mol Gen Genet 200:415–421. [PubMed]
116. Yokoyama K, Doi Y, Yamane K, Kurokawa H, Shibata N, Shibayama K, Yagi T, Kato H, Arakawa Y. 2003. Acquisition of 16S rRNA methylase gene in Pseudomonas aeruginosa. Lancet 362:1888–1893.
117. Wachino J, Shibayama K, Kurokawa H, Kimura K, Yamane K, Suzuki S, Shibata N, Ike Y, Arakawa Y. 2007. Novel plasmid-mediated 16S rRNA m1A1408 methyltransferase, NpmA, found in a clinically isolated Escherichia coli strain resistant to structurally diverse aminoglycosides. Antimicrob Agents Chemother 51:4401–4409. [PubMed]
118. Al Sheikh YA, Marie MA, John J, Krishnappa LG, Dabwab KH. 2014. Prevalence of 16S rRNA methylase genes among β-lactamase-producing Enterobacteriaceae clinical isolates in Saudi Arabia. Libyan J Med 9:24432. doi:10.3402/ljm.v9.24432.
119. Potron A, Poirel L, Nordmann P. 2015. Emerging broad-spectrum resistance in Pseudomonas aeruginosa and Acinetobacter baumannii: mechanisms and epidemiology. Int J Antimicrob Agents 45:568–585. [PubMed]
120. Zhou Y, Yu H, Guo Q, Xu X, Ye X, Wu S, Guo Y, Wang M. 2010. Distribution of 16S rRNA methylases among different species of Gram-negative bacilli with high-level resistance to aminoglycosides. Eur J Clin Microbiol Infect Dis 29:1349–1353. [PubMed]
121. Strateva T, Markova B, Markovska R, Marteva-Proevska Y, Ivanova D, Mitov I. 2011. Emergence of 16s rRNA methylase-producing nosocomial Acinetobacter baumannii isolates in a university hospital in Bulgaria. J Chemother 23:374–375. [PubMed]
122. Poole K. 2011. Pseudomonas aeruginosa: resistance to the max. Front Microbiol 2:65. doi:10.3389/fmicb.2011.00065. [PubMed]
123. Zacharczuk K, Piekarska K, Szych J, Jagielski M, Hidalgo L, San Millán A, Gutiérrez B, Rastawicki W, González-Zorn B, Gierczynski R. 2011. Plasmid-borne 16S rRNA methylase ArmA in aminoglycoside-resistant Klebsiella pneumoniae in Poland. J Med Microbiol 60:1306–1311. [PubMed]
124. Zacharczuk K, Piekarska K, Szych J, Zawidzka E, Sulikowska A, Wardak S, Jagielski M, Gierczynski R. 2011. Emergence of Klebsiella pneumoniae coproducing KPC-2 and 16S rRNA methylase ArmA in Poland. Antimicrob Agents Chemother 55:443–446. [PubMed]
125. Park YJ, Lee S, Yu JK, Woo GJ, Lee K, Arakawa Y. 2006. Co-production of 16S rRNA methylases and extended-spectrum beta-lactamases in AmpC-producing Enterobacter cloacae, Citrobacter freundii and Serratia marcescens in Korea. J Antimicrob Chemother 58:907–908. [PubMed]
126. Bercovier H, Kafri O, Sela S. 1986. Mycobacteria possess a surprisingly small number of ribosomal RNA genes in relation to the size of their genome. Biochem Biophys Res Commun 136:1136–1141.
127. Schwartz JJ, Gazumyan A, Schwartz I. 1992. rRNA gene organization in the Lyme disease spirochete, Borrelia burgdorferi. J Bacteriol 174:3757–3765. [PubMed]
128. Honoré N, Marchal G, Cole ST. 1995. Novel mutation in 16S rRNA associated with streptomycin dependence in Mycobacterium tuberculosis. Antimicrob Agents Chemother 39:769–770. [PubMed]
129. Meier A, Kirschner P, Bange FC, Vogel U, Böttger EC. 1994. Genetic alterations in streptomycin-resistant Mycobacterium tuberculosis: mapping of mutations conferring resistance. Antimicrob Agents Chemother 38:228–233. [PubMed]
130. Finken M, Kirschner P, Meier A, Wrede A, Böttger EC. 1993. Molecular basis of streptomycin resistance in Mycobacterium tuberculosis: alterations of the ribosomal protein S12 gene and point mutations within a functional 16S ribosomal RNA pseudoknot. Mol Microbiol 9:1239–1246. [PubMed]
131. Prammananan T, Sander P, Brown BA, Frischkorn K, Onyi GO, Zhang Y, Böttger EC, Wallace RJ Jr. 1998. A single 16S ribosomal RNA substitution is responsible for resistance to amikacin and other 2-deoxystreptamine aminoglycosides in Mycobacterium abscessus and Mycobacterium chelonae. J Infect Dis 177:1573–1581. [PubMed]
132. Criswell D, Tobiason VL, Lodmell JS, Samuels DS. 2006. Mutations conferring aminoglycoside and spectinomycin resistance in Borrelia burgdorferi. Antimicrob Agents Chemother 50:445–452. [PubMed]
133. Li XZ, Plésiat P, Nikaido H. 2015. The challenge of efflux-mediated antibiotic resistance in Gram-negative bacteria. Clin Microbiol Rev 28:337–418. [PubMed]
134. Poole K. 2004. Efflux-mediated multiresistance in Gram-negative bacteria. Clin Microbiol Infect 10:12–26. [PubMed]
135. Islam S, Jalal S, Wretlind B. 2004. Expression of the MexXY efflux pump in amikacin-resistant isolates of Pseudomonas aeruginosa. Clin Microbiol Infect 10:877–883. [PubMed]
136. Magnet S, Courvalin P, Lambert T. 2001. Resistance-nodulation-cell division-type efflux pump involved in aminoglycoside resistance in Acinetobacter baumannii strain BM4454. Antimicrob Agents Chemother 45:3375–3380. [PubMed]
137. Rosenberg EY, Ma D, Nikaido H. 2000. AcrD of Escherichia coli is an aminoglycoside efflux pump. J Bacteriol 182:1754–1756. [PubMed]
138. Moore RA, DeShazer D, Reckseidler S, Weissman A, Woods DE. 1999. Efflux-mediated aminoglycoside and macrolide resistance in Burkholderia pseudomallei. Antimicrob Agents Chemother 43:465–470. [PubMed]
139. Poole K. 2005. Efflux-mediated antimicrobial resistance. J Antimicrob Chemother 56:20–51. [PubMed]
140. Muller C, Plésiat P, Jeannot K. 2011. A two-component regulatory system interconnects resistance to polymyxins, aminoglycosides, fluoroquinolones, and β-lactams in Pseudomonas aeruginosa. Antimicrob Agents Chemother 55:1211–1221. [PubMed]
141. Singh M, Yau YCW, Wang S, Waters V, Kumar A. 2017. MexXY efflux pump overexpression and aminoglycoside resistance in cystic fibrosis isolates of Pseudomonas aeruginosa from chronic infections. Can J Microbiol 63:929–938. [PubMed]
142. Yoon EJ, Courvalin P, Grillot-Courvalin C. 2013. RND-type efflux pumps in multidrug-resistant clinical isolates of Acinetobacter baumannii: major role for AdeABC overexpression and AdeRS mutations. Antimicrob Agents Chemother 57:2989–2995. [PubMed]
143. Coyne S, Courvalin P, Périchon B. 2011. Efflux-mediated antibiotic resistance in Acinetobacter spp. Antimicrob Agents Chemother 55:947–953. [PubMed]
144. Zhao ZP, Liu TT, Zhang L, Luo M, Nie X, Li ZX, Pan Y. 2014. High-grade mutant OmpF induces decreased bacterial survival rate. Acta Biochim Pol 61:369–373. [PubMed]
145. Bryan LE, Kowand SK, Van Den Elzen HM. 1979. Mechanism of aminoglycoside antibiotic resistance in anaerobic bacteria: Clostridium perfringens and Bacteroides fragilis. Antimicrob Agents Chemother 15:7–13. [PubMed]
146. Lin YT, Huang YW, Liou RS, Chang YC, Yang TC. 2014. MacABCsm, an ABC-type tripartite efflux pump of Stenotrophomonas maltophilia involved in drug resistance, oxidative and envelope stress tolerances and biofilm formation. J Antimicrob Chemother 69:3221–3226. [PubMed]
147. Buroni S, Pasca MR, Flannagan RS, Bazzini S, Milano A, Bertani I, Venturi V, Valvano MA, Riccardi G. 2009. Assessment of three resistance-nodulation-cell division drug efflux transporters of Burkholderia cenocepacia in intrinsic antibiotic resistance. BMC Microbiol 9:200. doi:10.1186/1471-2180-9-200. [PubMed]
148. Jassem AN, Zlosnik JE, Henry DA, Hancock RE, Ernst RK, Speert DP. 2011. In vitro susceptibility of Burkholderia vietnamiensis to aminoglycosides. Antimicrob Agents Chemother 55:2256–2264. [PubMed]
149. Bador J, Amoureux L, Blanc E, Neuwirth C. 2013. Innate aminoglycoside resistance of Achromobacter xylosoxidans is due to AxyXY-OprZ, an RND-type multidrug efflux pump. Antimicrob Agents Chemother 57:603–605. [PubMed]
150. Li XZ, Zhang L, McKay GA, Poole K. 2003. Role of the acetyltransferase AAC(6′)-Iz modifying enzyme in aminoglycoside resistance in Stenotrophomonas maltophilia. J Antimicrob Chemother 51:803–811. [PubMed]
151. Costa Y, Galimand M, Leclercq R, Duval J, Courvalin P. 1993. Characterization of the chromosomal aac(6′)-Ii gene specific for E nterococcus faecium. Antimicrob Agents Chemother 37:1896–1903. [PubMed]
152. Galimand M, Schmitt E, Panvert M, Desmolaize B, Douthwaite S, Mechulam Y, Courvalin P. 2011. Intrinsic resistance to aminoglycosides in Enterococcus faecium is conferred by the 16S rRNA m5C1404-specific methyltransferase EfmM. RNA 17:251–262. [PubMed]
153. Cloutier D, Miller L, Komirenko A, Cebrik D, Keepers T, Krause K, Connolly L, Wagenlehner F. 2017. Evaluating once-daily plazomicin versus meropenem for the treatment of complicated urinary tract infection (cUTI) and acute pyelonephritis (AP): results from a phase 3 study (EPIC). ASM Microbe 2017, New Orleans, LA, 1 to 5 June 2017.
154. ZEMDRI™ (plazomicin). 2018. Full Prescribing Information. Achaogen Inc., South San Francisco, CA.
155. Connolly LE, Jubb A, O’Keeffe B, Serio A, Smith A, Gall J, Riddle V, Krause K, McKinnell J, Zakynthinos E, Daikos G. 2017. Plazomicin (PLZ) associated with improved survival and safety compared to colistin (CST) in the treatment of serious infections due to carbapenem-resistant Enterobacteriaceae (CRE): results of the CARE study. ASM Microbe 2017, New Orleans, LA, 1 to 5 June 2017.
156. Zárate G, De la Cruz Claure ML, Benito-Arenas R, Revuelta J, Santana AG, Bastida A. 2018. Overcoming aminoglycoside enzymatic resistance: design of novel antibiotics and inhibitors. Molecules 23:E284. doi:10.3390/molecules23020284. [PubMed]
157. Hobbie SN, Kalapala SK, Akshay S, Bruell C, Schmidt S, Dabow S, Vasella A, Sander P, Böttger EC. 2007. Engineering the rRNA decoding site of eukaryotic cytosolic ribosomes in bacteria. Nucleic Acids Res 35:6086–6093. [PubMed]
158. Mandhapati AR, Shcherbakov D, Duscha S, Vasella A, Böttger EC, Crich D. 2014. Importance of the 6′-hydroxy group and its configuration for apramycin activity. ChemMedChem 9:2074–2083. [PubMed]
159. Perez-Fernandez D, Shcherbakov D, Matt T, Leong NC, Kudyba I, Duscha S, Boukari H, Patak R, Dubbaka SR, Lang K, Meyer M, Akbergenov R, Freihofer P, Vaddi S, Thommes P, Ramakrishnan V, Vasella A, Böttger EC. 2014. 4′-O-substitutions determine selectivity of aminoglycoside antibiotics. Nat Commun 5:3112. doi:10.1038/ncomms4112. [PubMed]
160. Prokhorova I, Altman RB, Djumagulov M, Shrestha JP, Urzhumtsev A, Ferguson A, Chang CT, Yusupov M, Blanchard SC, Yusupova G. 2017. Aminoglycoside interactions and impacts on the eukaryotic ribosome. Proc Natl Acad Sci USA 114:E10899–E10908. [PubMed]
161. Greber BJ, Bieri P, Leibundgut M, Leitner A, Aebersold R, Boehringer D, Ban N. 2015. Ribosome. The complete structure of the 55S mammalian mitochondrial ribosome. Science 348:303–308. [PubMed]
162. Chandrika NT, Garneau-Tsodikova S. 2016. A review of patents (2011-2015) towards combating resistance to and toxicity of aminoglycosides. MedChemComm 7:50–68. [PubMed]
163. Houghton JL, Green KD, Chen W, Garneau-Tsodikova S. 2010. The future of aminoglycosides: the end or renaissance? ChemBioChem 11:880–902. [PubMed]
164. Dozzo P, Moser HE. 2010. New aminoglycoside antibiotics. Expert Opin Ther Pat 20:1321–1341. doi:10.1517/13543776.2010.506189. [PubMed]
165. Takahashi Y, Umemura E, Kobayashi Y, Murakami S, Nawa T, Morinaka A, Miyake T, Shibasaki M. 2018. Discovery of 2-hydroxyarbekacin, a new aminoglycoside antibiotic with reduced nephrotoxicity. J Antibiot (Tokyo) 71:345–347. [PubMed]
166. Sonousi A, Sarpe VA, Brilkova M, Schacht J, Vasella A, Böttger EC, Crich D. 2018. Effects of the 1-N-(4-Amino-2 S-hydroxybutyryl) and 6′-N-(2-Hydroxyethyl) substituents on ribosomal selectivity, cochleotoxicity, and antibacterial activity in the sisomicin class of aminoglycoside antibiotics. ACS Infect Dis 4:1114–1120. [PubMed]
167. Sati GC, Shcherbakov D, Hobbie SN, Vasella A, Böttger EC, Crich D. 2017. N6′, N6″, and O4′ Modifications to neomycin affect ribosomal selectivity without compromising antibacterial activity. ACS Infect Dis 3:368–377. [PubMed]
168. Duscha S, Boukari H, Shcherbakov D, Salian S, Silva S, Kendall A, Kato T, Akbergenov R, Perez-Fernandez D, Bernet B, Vaddi S, Thommes P, Schacht J, Crich D, Vasella A, Böttger EC. 2014. Identification and evaluation of improved 4′-O-(alkyl) 4,5-disubstituted 2-deoxystreptamines as next-generation aminoglycoside antibiotics. MBio 5:e01827-14. [PubMed]
169. Umemura E, Takahashi Y, Igarashi M, Hayashi C, Shibasaki M, Yamada K, Ida T, Yonezawa M, Ago K. TS3112, a novel aminoglycoside antibiotic active against multidrug-resistant pathogens producing 16S rRNA methyltransferases: synthesis and structure-activity relationships. ASM Microbe 2017, New Orleans, LA, 1 to 5 June 2017.
170. Yamada K, Takata T, Takayama Y, Senju N, Tabata Y, Ida T, Yonezawa M, Ago K. 2017. TS3112, a novel aminoglycoside antibiotic: in vitro and in vivo activity against multiple drug-resistant gram-positive and gram-negative pathogens. ASM Microbe 2017, New Orleans, LA, 1 to 5 June 2017.
171. Krause KM, Serio AW, Kane TR, Connolly LE. 2016. Aminoglycosides: an overview. Cold Spring Harb Perspect Med 6:a027029. doi:10.1101/cshperspect.a027029. [PubMed]
Loading

Article metrics loading...

/content/journal/ecosalplus/10.1128/ecosalplus.ESP-0002-2018
2018-11-16
2019-11-14

Abstract:

Aminoglycosides are cidal inhibitors of bacterial protein synthesis that have been utilized for the treatment of serious bacterial infections for almost 80 years. There have been approximately 15 members of this class approved worldwide for the treatment of a variety of infections, many serious and life threatening. While aminoglycoside use declined due to the introduction of other antibiotic classes such as cephalosporins, fluoroquinolones, and carbapenems, there has been a resurgence of interest in the class as multidrug-resistant pathogens have spread globally. Furthermore, aminoglycosides are recommended as part of combination therapy for empiric treatment of certain difficult-to-treat infections. The development of semisynthetic aminoglycosides designed to overcome common aminoglycoside resistance mechanisms, and the shift to once-daily dosing, has spurred renewed interest in the class. Plazomicin is the first new aminoglycoside to be approved by the FDA in nearly 40 years, marking the successful start of a new campaign to rejuvenate the class.

Highlighted Text: Show | Hide
Loading full text...

Full text loading...

/deliver/fulltext/ecosalplus/8/1/ESP-0002-2018.html?itemId=/content/journal/ecosalplus/10.1128/ecosalplus.ESP-0002-2018&mimeType=html&fmt=ahah
Comment has been disabled for this content
Submit comment
Close
Comment moderation successfully completed

Figures

Image of Figure 1

Click to view

Figure 1

(A) Positively charged aminoglycosides (AG) enter the cell via electrostatic binding to the negatively charged components of the outer membrane (OM) including phospholipids and LPS in Gram-negative bacteria or teichoic acid in Gram-positive bacteria. This binding allows access of the AG to the periplasmic space. (B) A small number of AGs cross the inner membrane (IM) using the proton motive force and into the cytoplasm in an energy-dependent manner. (C) In the cytoplasm, AGs bind the 16S rRNA of the 30S ribosomal subunit where they inhibit initiation of translation, block elongation of translation, and induce error-prone translation. Mistranslated proteins are hypothesized to cause damage to the IM, facilitating AG entry into the cytoplasm.

Citation: Serio A, Keepers T, Andrews L, Krause K. 2018. Aminoglycoside Revival: Review of a Historically Important Class of Antimicrobials Undergoing Rejuvenation, EcoSal Plus 2018; doi:10.1128/ecosalplus.ESP-0002-2018
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2

Click to view

Figure 2

Structures of representative aminoglycosides, including the atypical aminoglycosides streptomycin and apramycin, 4,6-substituted amikacin and the 4,5-substituted neomycin B. The deoxystreptamine or streptidine rings are in bold. ©Cold Spring Harbor Press ( 171 ), used with permission.

Citation: Serio A, Keepers T, Andrews L, Krause K. 2018. Aminoglycoside Revival: Review of a Historically Important Class of Antimicrobials Undergoing Rejuvenation, EcoSal Plus 2018; doi:10.1128/ecosalplus.ESP-0002-2018
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3

Click to view

Figure 3

(A) An example of chemical modification of gentamicin catalyzed by aminoglycoside acetyltransferase AAC(3). (B) An example of chemical modification of amikacin catalyzed by aminoglycoside phosphotransferase APH(3′). (C) An example of chemical modification of kanamycin catalyzed by the aminoglycoside nucleotidyltransferase ANT(2″). ©Cold Spring Harbor Press ( 171 ), used with permission.

Citation: Serio A, Keepers T, Andrews L, Krause K. 2018. Aminoglycoside Revival: Review of a Historically Important Class of Antimicrobials Undergoing Rejuvenation, EcoSal Plus 2018; doi:10.1128/ecosalplus.ESP-0002-2018
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 4

Click to view

Figure 4

(A) Kanamycin B scaffold with modification to dibekacin and subsequent modification to arbekacin. (B) Kanamycin A scaffold with modification to amikacin. (C) Gentamicin B scaffold with modification to isepamicin. (D) Sisomicin scaffold with modification to netilmicin and with modification to plazomicin. Green highlights indicate new chemical modifications; green circles indicate removal of hydroxyl groups.

Citation: Serio A, Keepers T, Andrews L, Krause K. 2018. Aminoglycoside Revival: Review of a Historically Important Class of Antimicrobials Undergoing Rejuvenation, EcoSal Plus 2018; doi:10.1128/ecosalplus.ESP-0002-2018
Permissions and Reprints Request Permissions
Download as Powerpoint

Tables

Generic image for table

Click to view

Table 1

16S ribosomal RNA methyltransferase classes

Citation: Serio A, Keepers T, Andrews L, Krause K. 2018. Aminoglycoside Revival: Review of a Historically Important Class of Antimicrobials Undergoing Rejuvenation, EcoSal Plus 2018; doi:10.1128/ecosalplus.ESP-0002-2018

Supplemental Material

No supplementary material available for this content.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error