Plazomicin: a New Aminoglycoside in the Fight Against Antimicrobial Resistance

Overview

Journal Ther Adv Infect Dis

Publisher Sage Publications

Specialty Infectious Diseases

Date 2020 Sep 21

PMID 32953108

Citations 18

Authors

Justin A Clark

David S Burgess

Affiliations

Soon will be listed here.

Abstract

Objective: To review the mechanism of action, mechanisms of resistance, activity, pharmacokinetics, pharmacodynamics, and clinical data for a novel aminoglycoside.

Data Sources: A PubMed search was performed from January 2006 to August 2019 using the following search terms: plazomicin and ACHN-490. Another search was conducted on clinicaltrials.gov for published clinical data. References from selected studies were also used to find additional literature.

Study Selection And Data Extraction: All English-language studies presenting original research (, pharmacokinetic, and clinical) were evaluated.

Data Synthesis: Plazomicin has activity against several multi-drug-resistant organisms, including carbapenem-resistant . It was Food and Drug Administration (FDA) approved to treat complicated urinary tract infections (cUTIs), including acute pyelonephritis, following phase II and III trials compared with levofloxacin and meropenem, respectively. Despite the FDA Black Box Warning for aminoglycoside class effects (nephrotoxicity, ototoxicity, neuromuscular blockade, and pregnancy risk), it exhibited a favorable safety profile with the most common adverse effects being decreased renal function (3.7%), diarrhea (2.3%), hypertension (2.3%), headache (1.3%), nausea (1.3%), vomiting (1.3%), and hypotension (1.0%) in the largest in-human trial.

Relevance To Patient Care And Clinical Practice: Plazomicin will likely be used in the treatment of multi-drug-resistant cUTIs or in combination to treat serious carbapenem-resistant infections.

Conclusions: Plazomicin appears poised to help fill the need for new agents to treat infections caused by multi-drug-resistant .

Citing Articles

Mechanisms, therapeutic strategies, and emerging therapeutic alternatives for carbapenem resistance in Gram-negative bacteria.

Mourabiti F, Jouga F, Sakoui S, El Hosayny O, Zouheir Y, Soukri A Arch Microbiol. 2025; 207(3):58.

PMID: 39948320 DOI: 10.1007/s00203-025-04252-z.

Forecasting the development of antimicrobial resistance of .

Shemetov O, Faustova M, Perepelova T, Balia H, Pavlish I, Loban G Front Oral Health. 2025; 5():1514070.

PMID: 39850470 PMC: 11754302. DOI: 10.3389/froh.2024.1514070.

Tackling the outer membrane: facilitating compound entry into Gram-negative bacterial pathogens.

Saxena D, Maitra R, Bormon R, Czekanska M, Meiers J, Titz A NPJ Antimicrob Resist. 2025; 1(1):17.

PMID: 39843585 PMC: 11721184. DOI: 10.1038/s44259-023-00016-1.

Antibiotic Resistance in the Elderly: Mechanisms, Risk Factors, and Solutions.

Theodorakis N, Feretzakis G, Hitas C, Kreouzi M, Kalantzi S, Spyridaki A Microorganisms. 2024; 12(10).

PMID: 39458286 PMC: 11509523. DOI: 10.3390/microorganisms12101978.

A dual-function chromogenic and fluorogenic benzofurazan probe for plazomicin and its innovative utility for development of two microwell assays with high throughput for analysis of drug substance and pharmaceutical formulations.

Alkathiri F, Al-Outaibi M, Darwish I RSC Adv. 2024; 14(37):27215-27226.

PMID: 39193289 PMC: 11348761. DOI: 10.1039/d4ra04882b.

References

Logan L, Weinstein R . The Epidemiology of Carbapenem-Resistant Enterobacteriaceae: The Impact and Evolution of a Global Menace. J Infect Dis. 2017; 215(suppl_1):S28-S36. PMC: 5853342. DOI: 10.1093/infdis/jiw282. View

Garneau-Tsodikova S, Labby K . Mechanisms of Resistance to Aminoglycoside Antibiotics: Overview and Perspectives. Medchemcomm. 2016; 7(1):11-27. PMC: 4752126. DOI: 10.1039/C5MD00344J. View

Shields R, Nguyen M, Press E, Chen L, Kreiswirth B, Clancy C . Emergence of Ceftazidime-Avibactam Resistance and Restoration of Carbapenem Susceptibility in Carbapenemase-Producing : A Case Report and Review of Literature. Open Forum Infect Dis. 2017; 4(3):ofx101. PMC: 5493938. DOI: 10.1093/ofid/ofx101. View

Abdelraouf K, Kim A, Krause K, Nicolau D . Efficacy of Plazomicin Alone or in Combination with Meropenem or Tigecycline against Enterobacteriaceae Isolates Exhibiting Various Resistance Mechanisms in an Immunocompetent Murine Septicemia Model. Antimicrob Agents Chemother. 2018; 62(8). PMC: 6105799. DOI: 10.1128/AAC.01074-18. View

Asempa T, Kuti J, Seroogy J, Komirenko A, Nicolau D . Application of the Hartford Hospital Nomogram for Plazomicin Dosing Interval Selection in Patients with Complicated Urinary Tract Infection. Antimicrob Agents Chemother. 2019; 63(10). PMC: 6761540. DOI: 10.1128/AAC.00148-19. View

Walkty A, Adam H, Baxter M, Denisuik A, Lagace-Wiens P, Karlowsky J . In vitro activity of plazomicin against 5,015 gram-negative and gram-positive clinical isolates obtained from patients in canadian hospitals as part of the CANWARD study, 2011-2012. Antimicrob Agents Chemother. 2014; 58(5):2554-63. PMC: 3993217. DOI: 10.1128/AAC.02744-13. View

Castanheira M, Deshpande L, Woosley L, Serio A, Krause K, Flamm R . Activity of plazomicin compared with other aminoglycosides against isolates from European and adjacent countries, including Enterobacteriaceae molecularly characterized for aminoglycoside-modifying enzymes and other resistance mechanisms. J Antimicrob Chemother. 2018; 73(12):3346-3354. DOI: 10.1093/jac/dky344. View

Thwaites M, Hall D, Shinabarger D, Serio A, Krause K, Marra A . Evaluation of the Bactericidal Activity of Plazomicin and Comparators against Multidrug-Resistant Enterobacteriaceae. Antimicrob Agents Chemother. 2018; 62(8). PMC: 6105851. DOI: 10.1128/AAC.00236-18. View

Mingeot-Leclercq M, Glupczynski Y, Tulkens P . Aminoglycosides: activity and resistance. Antimicrob Agents Chemother. 1999; 43(4):727-37. PMC: 89199. DOI: 10.1128/AAC.43.4.727. View

10.

Kuti J, Kim A, Cloutier D, Nicolau D . Evaluation of Plazomicin, Tigecycline, and Meropenem Pharmacodynamic Exposure against Carbapenem-Resistant Enterobacteriaceae in Patients with Bloodstream Infection or Hospital-Acquired/Ventilator-Associated Pneumonia from the CARE Study.... Infect Dis Ther. 2019; 8(3):383-396. PMC: 6702525. DOI: 10.1007/s40121-019-0251-4. View

11.

de Kraker M, Stewardson A, Harbarth S . Will 10 Million People Die a Year due to Antimicrobial Resistance by 2050?. PLoS Med. 2016; 13(11):e1002184. PMC: 5127510. DOI: 10.1371/journal.pmed.1002184. View

12.

Castanheira M, Davis A, Mendes R, Serio A, Krause K, Flamm R . Activity of Plazomicin against Gram-Negative and Gram-Positive Isolates Collected from U.S. Hospitals and Comparative Activities of Aminoglycosides against Carbapenem-Resistant Enterobacteriaceae and Isolates Carrying Carbapenemase Genes. Antimicrob Agents Chemother. 2018; 62(8). PMC: 6105795. DOI: 10.1128/AAC.00313-18. View

13.

Landman D, Babu E, Shah N, Kelly P, Backer M, Bratu S . Activity of a novel aminoglycoside, ACHN-490, against clinical isolates of Escherichia coli and Klebsiella pneumoniae from New York City. J Antimicrob Chemother. 2010; 65(10):2123-7. DOI: 10.1093/jac/dkq278. View

14.

Cox G, Ejim L, Stogios P, Koteva K, Bordeleau E, Evdokimova E . Plazomicin Retains Antibiotic Activity against Most Aminoglycoside Modifying Enzymes. ACS Infect Dis. 2018; 4(6):980-987. PMC: 6167752. DOI: 10.1021/acsinfecdis.8b00001. View

15.

Drusano G, Ambrose P, Bhavnani S, Bertino J, Nafziger A, Louie A . Back to the future: using aminoglycosides again and how to dose them optimally. Clin Infect Dis. 2007; 45(6):753-60. DOI: 10.1086/520991. View

16.

Abat C, Rolain J, Dubourg G, Fournier P, Chaudet H, Raoult D . Evaluating the Clinical Burden and Mortality Attributable to Antibiotic Resistance: The Disparity of Empirical Data and Simple Model Estimations. Clin Infect Dis. 2017; 65(suppl_1):S58-S63. DOI: 10.1093/cid/cix346. View

17.

Martins A, Bail L, Ito C, Nogueira K, Dalmolin T, Martins A . Antimicrobial activity of plazomicin against Enterobacteriaceae-producing carbapenemases from 50 Brazilian medical centers. Diagn Microbiol Infect Dis. 2017; 90(3):228-232. DOI: 10.1016/j.diagmicrobio.2017.11.004. View

18.

McKinnell J, Dwyer J, Talbot G, Connolly L, Friedland I, Smith A . Plazomicin for Infections Caused by Carbapenem-Resistant Enterobacteriaceae. N Engl J Med. 2019; 380(8):791-793. DOI: 10.1056/NEJMc1807634. View

19.

Nordmann P, Jayol A, Dobias J, Poirel L . Rapid Aminoglycoside NP Test for Rapid Detection of Multiple Aminoglycoside Resistance in Enterobacteriaceae. J Clin Microbiol. 2017; 55(4):1074-1079. PMC: 5377834. DOI: 10.1128/JCM.02107-16. View

20.

Taylor E, Sriskandan S, Woodford N, Hopkins K . High prevalence of 16S rRNA methyltransferases among carbapenemase-producing Enterobacteriaceae in the UK and Ireland. Int J Antimicrob Agents. 2018; 52(2):278-282. DOI: 10.1016/j.ijantimicag.2018.03.016. View