title: Plazomicin: an investigational therapy for the treatment of urinary tract infections.
abstract: BACKGROUND
  Living in the ever-expanding era of multidrug-resistant (MDR), extensively drug-resistant (XDR), and even pandrug-resistant Gram-negative microorganisms, the medical community is facing the approaching fear of the "End of Antibiotics." Plazomicin is a next-generation aminoglycoside designed to evade all clinically relevant aminoglycoside-modifying enzymes, the main mechanism of aminoglycoside resistance. A newer aminoglycoside active against several MDR-XDR microorganisms is herein presented and discussed.
  
  
  METHODS
  Herein, the authors present the currently available information on plazomicin. This includes the current knowledge concerning plazomicin's: mechanisms of action, in vitro activity and interactions, its pharmacokinetics, its clinical efficacy in complicated urinary tract infections (cUTIs) and acute pyelonephritis, and its toxicity issues.
  
  
  CONCLUSIONS
  Plazomicin was developed to evade all clinically relevant aminoglycoside-modifying enzymes. Unfortunately, ribosomal enzymatic modification by ribosomal 16S-rRNA methyltransferases confers broad-spectrum high-level aminoglycoside resistance. Still, plazomicin demonstrates high activity against the Enterobacteriaceae including extended spectrum beta lactamase and most carbapenemase producers, as well as several of the non-fermenters. When compared to levofloxacin, the in vivo activity of plazomicin in complicated urinary tract infections (cUTIs) and in acute pyelonephritis in humans was very promising. Furthermore, regarding safety, no clinically significant effects on renal, vestibular, or cochlear function have been observed both at Phase I and II studies in humans, with mild to moderate adverse events being dose related. However, the authors believe that the real position of plazomicin in the MDR-XDR world will be revealed once pending Phase III studies are completed.
authors.affiliation: a 1 Hygeia General Hospital, 6th Department of Internal Medicine , 4, Erythrou Stavrou street & Kifisias avenue, Athens 15123, Greece.
authors.forename: Ilias
authors.initials: I
authors.lastname: Karaiskos
authors.affiliation: b 2 University General Hospital Attikon, 4th Dpt Internal Medicine , 1 Rimini street, Chaidari Athens 124 62, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Souli
authors.affiliation: c 3 Hygeia General Hospital, 6th Department of Internal Medicine , 4, Erythrou Stavrou street & Kifisias avenue, Marousi, Athens 15123, Greece +30 21 06 86 79 46 ; +30 21 06 86 73 77 ; e.giamarellou@hygeia.gr.
authors.forename: Helen
authors.initials: H
authors.lastname: Giamarellou
mesh_terms: D000208:Acute Disease; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D024901:Drug Resistance, Multiple, Bacterial; D006801:Humans; D011704:Pyelonephritis / Q000188:drug therapy; D012853:Sisomicin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D014552:Urinary Tract Infections / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; C550938:plazomicin; D012853:Sisomicin
keywords: ACHN-490; acute pyelonephritis; aminoglycoside; multidrug-resistant; novel antibiotics; plazomicin; urinary tract infections