Plazomicin Explained

Pronounce:pla" zoe mye' sin
Tradename:Zemdri
Dailymedid:Plazomicin
Routes Of Administration:Intravenous
Class:Aminoglycoside
Atc Prefix:J01
Atc Suffix:GB14
Legal Us:Rx-only
Index2 Label:as salt
Cas Number:1154757-24-0
Pubchem:42613186
Drugbank:DB12615
Chemspiderid:26390008
Unii:LYO9XZ250J
Kegg:D10151
Kegg2:D10655
Chembl:1650559
Pdb Ligand:EDS
Synonyms:ACHN-490,
6'-(Hydroxylethyl)-1-(HABA)-sisomicin
Iupac Name:(2S)-4-Amino-N-[(1''R'',2''S'',3''S'',4''R'',5''S'')-5-amino-4-[[(2''S'',3''R'')-3-amino-6-[(2-hydroxyethylamino)methyl]-3,4-dihydro-2H-pyran-2-yl]oxy]-2-[(2''R'',3''R'',4''R'',5''R'')-3,5-dihydroxy-5-methyl-4-(methylamino)oxan-2-yl]oxy-3-hydroxycyclohexyl]-2-hydroxybutanamide
C:25
H:48
N:6
O:10
Smiles:CN[C@@H]1[C@@H](O)[C@@H](O[C@@H]2[C@@H](O)[C@H](O[C@H]3OC(=CC[C@H]3N)CNCCO)[C@@H](N)C[C@H]2NC(=O)[C@@H](O)CCN)OC[C@]1(C)O
Stdinchi:1S/C25H48N6O10/c1-25(37)11-38-24(18(35)21(25)29-2)41-20-15(31-22(36)16(33)5-6-26)9-14(28)19(17(20)34)40-23-13(27)4-3-12(39-23)10-30-7-8-32/h3,13-21,23-24,29-30,32-35,37H,4-11,26-28H2,1-2H3,(H,31,36)/t13-,14+,15-,16+,17+,18-,19-,20+,21-,23-,24-,25+/m1/s1
Stdinchikey:IYDYFVUFSPQPPV-PEXOCOHZSA-N

Plazomicin, sold under the brand name Zemdri, is an aminoglycoside antibiotic used to treat complicated urinary tract infections.[1] As of 2019 it is recommended only for those in whom alternatives are not an option.[1] It is given by injection into a vein.[1]

Common side effects include kidney problems, diarrhea, nausea, and blood pressure changes.[1] Other severe side effects include hearing loss, Clostridium difficile-associated diarrhea, anaphylaxis, and muscle weakness.[1] Use during pregnancy may harm the baby.[1] Plazomicin works by decreasing the ability of bacteria to make protein.[1]

Plazomicin was approved for medical use in the United States in 2018.[2] It is on the World Health Organization's List of Essential Medicines.[3]

Medical uses

Plazomicin is approved by the U.S. Food and Drug Administration (FDA) for adults with complicated urinary tract infections, including pyelonephritis, caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, or Enterobacter cloacae, in patients who have limited or no alternative treatment options. Zemdri is an intravenous infusion, administered once daily.[4] [5] [6] [7] The FDA declined approval for treating bloodstream infections due to lack of demonstrated effectiveness.[8] The lack of demonstrated effectiveness was not so much about the antibiotic itself being ineffective so much as the low enrollment rate for the study. Studies using mouse models however, showed a high survival rate.[9]

Plazomicin has been reported to demonstrate in vitro synergistic activity when combined with daptomycin or ceftobiprole versus methicillin-resistant Staphylococcus aureus, vancomycin-resistant S. aureus and against Pseudomonas aeruginosa when combined with cefepime, doripenem, imipenem or piperacillin/tazobactam. It also demonstrates potent in vitro activity versus carbapenem-resistant Acinetobacter baumannii.[10] Plazomicin was found to be noninferior to meropenem.[11]

History

The drug was developed by the biotech company Achaogen. In 2012, the U.S. Food and Drug Administration granted fast track designation for the development and regulatory review of plazomicin.[12] The FDA approved plazomicin for adults with complicated UTIs and limited or no alternative treatment options in 2018. Achaogen was unable to find a robust market for the drug, and declared bankruptcy a few months later.[13] A generic version is manufactured by Cipla USA.[14]

Synthesis

It is derived from sisomicin by appending a hydroxy-aminobutyric acid substituent at position 1 and a hydroxyethyl substituent at position 6'.[15] [16] The latter makes it impervious to acetylation (deactivation) by Aminoglycoside Acetyltransferase 6'-N- Type Ib (AAC(6')-Ib), the most prevalent AAC enzyme.[17]

Names

Plazomicin is the international nonproprietary name (INN).[18]

Further reading

Notes and References

  1. Web site: Plazomicin Sulfate Monograph for Professionals . Drugs.com . American Society of Health-System Pharmacists . 10 October 2019 . 6 August 2020 . https://web.archive.org/web/20200806090108/https://www.drugs.com/monograph/plazomicin-sulfate.html . live .
  2. Web site: Drug Approval Package: Zemdri (plazomicin) . . 5 July 2018 . 25 December 2019 . 28 November 2020 . https://web.archive.org/web/20201128083016/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210303Orig1s000TOC.cfm . live .
  3. Book: ((World Health Organization)) . World Health Organization model list of essential medicines: 21st list 2019 . 2019 . 10665/325771 . World Health Organization . World Health Organization . Geneva . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO . free .
  4. Web site: Zemdri (plazomicin)- plazomicin injection . DailyMed . 30 July 2020 . 11 October 2020 . 22 February 2021 . https://web.archive.org/web/20210222123651/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=eccf9fd9-53ac-4252-a106-5567b3a82a70 . live .
  5. Web site: plazomicin (Rx). Medscape. 14 September 2019. 28 November 2020. https://web.archive.org/web/20201128083055/https://reference.medscape.com/drug/zemdri-plazomicin-1000230. live.
  6. Web site: FDA Panel Recommends Plazomicin for cUTI but Not BSI . Brown T . 3 May 2018 . Medscape . 14 September 2019 . vanc . 25 November 2020 . https://web.archive.org/web/20201125230711/https://www.medscape.com/viewarticle/896116 . live .
  7. Web site: BioCentury - FDA approves plazomicin for cUTI, but not blood infections. www.biocentury.com. 2018-06-28. 14 August 2020. https://web.archive.org/web/20200814005525/https://www.biocentury.com/bc-extra/company-news/2018-06-26/fda-approves-plazomicin-cuti-not-blood-infections. live.
  8. Web site: FDA Approved Drug Products: Zemdri. U.S. Food and Drug Administration. 2018-06-28. dmy-all. 28 November 2020. https://web.archive.org/web/20201128080033/https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=210303. live.
  9. Web site: Plazomicin . fda.gov . Antimicrobial Drugs Advisory Committee . https://web.archive.org/web/20201227012808/https://www.fda.gov/media/113289/download . December 27, 2020 . May 2, 2018 . dead.
  10. García-Salguero C, Rodríguez-Avial I, Picazo JJ, Culebras E . 3 . Can Plazomicin Alone or in Combination Be a Therapeutic Option against Carbapenem-Resistant Acinetobacter baumannii?. Antimicrob Agents Chemother. October 2015. 59. 10. 5959–66. 10.1128/AAC.00873-15. 26169398. 4576036.
  11. Wagenlehner FM, Cloutier DJ, Komirenko AS, Cebrik DS, Krause KM, Keepers TR, Connolly LE, Miller LG, Friedland I, Dwyer JP . 3 . Once-Daily Plazomicin for Complicated Urinary Tract Infections . New England Journal of Medicine . 380 . 8 . 21 February 2019 . 0028-4793 . 10.1056/nejmoa1801467 . 729–740 . 30786187 . free .
  12. Achaogen Announces Plazomicin Granted QIDP Designation by FDA. GlobeNewswire. Achaogen, Inc.. 8 January 2015. 27 April 2016. 28 April 2016. https://web.archive.org/web/20160428013854/https://globenewswire.com/news-release/2015/01/08/695854/10114610/en/Achaogen-Announces-Plazomicin-Granted-QIDP-Designation-by-FDA.html. live.
  13. News: Crisis Looms in Antibiotics as Drug Makers Go Bankrupt. The New York Times. 25 December 2019. Jacobs A. 12 July 2024. 1 February 2021. https://web.archive.org/web/20210201230345/https://www.nytimes.com/2019/12/25/health/antibiotics-new-resistance.html. live.
  14. Web site: Generic Zemdri Availability . Drugs.com . 26 December 2019 . en . 6 August 2020 . https://web.archive.org/web/20200806083922/https://www.drugs.com/availability/generic-zemdri.html . live .
  15. 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 . 6 . Synthesis and spectrum of the neoglycoside ACHN-490 . Antimicrobial Agents and Chemotherapy . 54 . 11 . 4636–4642 . November 2010 . 20805391 . 2976124 . 10.1128/AAC.00572-10 .
  16. Zhanel GG, Lawson CD, Zelenitsky S, Findlay B, Schweizer F, Adam H, Walkty A, Rubinstein E, Gin AS, Hoban DJ, Lynch JP, Karlowsky JA . 6 . Comparison of the next-generation aminoglycoside plazomicin to gentamicin, tobramycin and amikacin . Expert Review of Anti-Infective Therapy . 10 . 4 . 459–473 . April 2012 . 22512755 . 10.1586/eri.12.25 . 31496981 .
  17. Cox G, Ejim L, Stogios PJ, Koteva K, Bordeleau E, Evdokimova E, Sieron AO, Savchenko A, Serio AW, Krause KM, Wright GD . 6 . Plazomicin Retains Antibiotic Activity against Most Aminoglycoside Modifying Enzymes . ACS Infectious Diseases . 4 . 6 . 980–987 . June 2018 . 29634241 . 6167752 . 10.1021/acsinfecdis.8b00001 .
  18. International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended INN: List 68 . WHO Drug Information . 26 . 3 . September 2012 . https://web.archive.org/web/20141002045030/http://www.who.int/medicines/publications/druginformation/issues/DrugInformation2012_Vol26-3/en/ . dead . 2 October 2014 . . 27 April 2016 . 314.

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