View source for Plazomicin

{{Short description|Antibiotic medication}}
{{Use dmy dates|date=September 2019}}
{{Infobox drug
| image             = Plazomicin structure.svg
| width             =
| alt               =
| caption           =

<!-- Clinical data -->
| pronounce         = pla" zoe mye' sin
| tradename         = Zemdri
| Drugs.com         = {{drugs.com|monograph|plazomicin-sulfate}}
| MedlinePlus       = a618037
| DailyMedID        = Plazomicin
| pregnancy_AU      = <!-- A/B1/B2/B3/C/D/X -->
| pregnancy_AU_comment =
| pregnancy_category=
| routes_of_administration = [[Intravenous therapy|Intravenous]]
| class             = [[Aminoglycoside]]
| ATC_prefix        = J01
| ATC_suffix        = GB14
| ATC_supplemental  =

<!-- Legal status -->
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled-->
| legal_AU_comment =
| legal_BR =  <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F-->
| legal_BR_comment =
| legal_CA          = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_CA_comment  =
| legal_DE = <!-- Anlage I, II, III or Unscheduled-->
| legal_DE_comment =
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment =
| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->
| legal_UK_comment =
| legal_US = Rx-only
| legal_US_comment =
| legal_EU =
| legal_EU_comment =
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV-->
| legal_UN_comment =
| legal_status      = <!--For countries not listed above-->

<!-- Pharmacokinetic data -->
| bioavailability   =
| protein_bound     =
| metabolism        =
| metabolites       =
| onset             =
| elimination_half-life =
| duration_of_action =
| excretion         =

<!-- Identifiers -->
| index2_label = as salt
| CAS_number        = 1154757-24-0
| CAS_supplemental  =
| PubChem           = 42613186
| IUPHAR_ligand     =
| DrugBank          = DB12615
| ChemSpiderID      = 26390008
| UNII              = LYO9XZ250J
| KEGG              = D10151
| KEGG2             = D10655
| ChEBI             =
| ChEMBL            = 1650559
| NIAID_ChemDB      =
| PDB_ligand        = EDS
| synonyms          = ACHN-490,<br />6'-(Hydroxylethyl)-1-(HABA)-sisomicin

<!-- Chemical and physical data -->
| IUPAC_name        = (2''S'')-4-Amino-''N''-[(1''R'',2''S'',3''S'',4''R'',5''S'')-5-amino-4-<nowiki>[[</nowiki>(2''S'',3''R'')-3-amino-6-[(2-hydroxyethylamino)methyl]-3,4-dihydro-2''H''-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
| StdInChI_comment  =
| StdInChIKey       = IYDYFVUFSPQPPV-PEXOCOHZSA-N
| density           =
| density_notes     =
| melting_point     =
| melting_high      =
| melting_notes     =
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| specific_rotation =
}}

<!-- Definition and symptoms -->
'''Plazomicin''', sold under the brand name '''Zemdri''', is an [[aminoglycoside antibiotic]] used to treat complicated [[urinary tract infections]].<ref name=AHFS2019>{{cite web |title=Plazomicin Sulfate Monograph for Professionals |url=https://www.drugs.com/monograph/plazomicin-sulfate.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |access-date=10 October 2019 |archive-date=6 August 2020 |archive-url=https://web.archive.org/web/20200806090108/https://www.drugs.com/monograph/plazomicin-sulfate.html |url-status=live }}</ref> As of 2019 it is recommended only for those in whom alternatives are not an option.<ref name=AHFS2019/> It is given by [[injection into a vein]].<ref name=AHFS2019/>

<!-- Side effect and mechanism -->
Common side effects include [[kidney problems]], [[diarrhea]], nausea, and blood pressure changes.<ref name=AHFS2019/> Other severe side effects include [[hearing loss]], [[Clostridioides difficile infection|''Clostridioides difficile''-associated diarrhea]], [[anaphylaxis]], and muscle weakness.<ref name=AHFS2019/> Use during pregnancy may harm the baby.<ref name=AHFS2019/> Plazomicin works by decreasing the ability of bacteria to make protein.<ref name=AHFS2019/>

<!-- History and culture -->
Plazomicin was approved for medical use in the United States in 2018.<ref name="FDA Zemdri 210303" /><ref>{{cite web | title=Drug Approval Package: Zemdri (plazomicin) | website=U.S. [[Food and Drug Administration]] | date=5 July 2018 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210303Orig1s000TOC.cfm | access-date=25 December 2019 | archive-date=28 November 2020 | archive-url=https://web.archive.org/web/20201128083016/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210303Orig1s000TOC.cfm | url-status=live }}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref>

==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.<ref name="Zemdri label">{{cite web | title=Zemdri (plazomicin)- plazomicin injection | website=DailyMed | date=30 July 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=eccf9fd9-53ac-4252-a106-5567b3a82a70 | access-date=11 October 2020 | archive-date=22 February 2021 | archive-url=https://web.archive.org/web/20210222123651/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=eccf9fd9-53ac-4252-a106-5567b3a82a70 | url-status=live }}</ref><ref>{{Cite web|url=https://reference.medscape.com/drug/zemdri-plazomicin-1000230|title=plazomicin (Rx)|website=[[Medscape]]|access-date=14 September 2019|archive-date=28 November 2020|archive-url=https://web.archive.org/web/20201128083055/https://reference.medscape.com/drug/zemdri-plazomicin-1000230|url-status=live}}</ref><ref>{{cite web | title=FDA Panel Recommends Plazomicin for cUTI but Not BSI | vauthors=Brown T | date=3 May 2018 | website=Medscape | url=http://www.medscape.com/viewarticle/896116 | access-date=14 September 2019 | name-list-style=vanc | archive-date=25 November 2020 | archive-url=https://web.archive.org/web/20201125230711/https://www.medscape.com/viewarticle/896116 | url-status=live }}</ref><ref>{{Cite web|url=https://www.biocentury.com/bc-extra/company-news/2018-06-26/fda-approves-plazomicin-cuti-not-blood-infections|title=BioCentury - FDA approves plazomicin for cUTI, but not blood infections|website=www.biocentury.com|access-date=2018-06-28|archive-date=14 August 2020|archive-url=https://web.archive.org/web/20200814005525/https://www.biocentury.com/bc-extra/company-news/2018-06-26/fda-approves-plazomicin-cuti-not-blood-infections|url-status=live}}</ref> The FDA declined approval for treating bloodstream infections due to lack of demonstrated effectiveness.<ref name="FDA Zemdri 210303">{{Cite web|url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=210303|title=FDA Approved Drug Products: Zemdri|website=U.S. [[Food and Drug Administration]]|access-date=2018-06-28|df=dmy-all|archive-date=28 November 2020|archive-url=https://web.archive.org/web/20201128080033/https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=210303|url-status=live}}</ref> 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.<ref>{{cite web |title=Plazomicin |url=https://www.fda.gov/media/113289/download |website=fda.gov |publisher=Antimicrobial Drugs Advisory Committee |archive-url=https://web.archive.org/web/20201227012808/https://www.fda.gov/media/113289/download |archive-date=December 27, 2020 |date=May 2, 2018 |url-status=dead}}</ref>

Plazomicin has been reported to demonstrate ''in vitro'' synergistic activity when combined with [[daptomycin]] or [[ceftobiprole]] versus [[Methicillin-resistant Staphylococcus aureus|methicillin-resistant ''Staphylococcus aureus'']], [[Vancomycin-resistant Staphylococcus aureus|vancomycin-resistant ''S. aureus'']] and against ''[[Pseudomonas aeruginosa]]'' when combined with [[cefepime]], [[doripenem]], [[imipenem]] or [[piperacillin/tazobactam]].<ref name="Zhanel" /> It also demonstrates potent ''in vitro'' activity versus carbapenem-resistant ''[[Acinetobacter baumannii]]''.<ref>{{cite journal| vauthors=García-Salguero C, Rodríguez-Avial I, Picazo JJ, Culebras E | display-authors=3 |title=Can Plazomicin Alone or in Combination Be a Therapeutic Option against Carbapenem-Resistant ''Acinetobacter baumannii''?|journal=Antimicrob Agents Chemother|date=October 2015|volume=59|issue=10|pages=5959–66|doi=10.1128/AAC.00873-15|url= |pmid=26169398|pmc=4576036}}</ref> Plazomicin was found to be noninferior to meropenem.<ref>{{clinicalTrialsGov|NCT02486627|A Study of Plazomicin Compared With Meropenem for the Treatment of Complicated Urinary Tract Infection (cUTI) Including Acute Pyelonephritis (AP) (EPIC)}}</ref><ref>{{cite journal | vauthors=Wagenlehner FM, Cloutier DJ, Komirenko AS, Cebrik DS, Krause KM, Keepers TR, Connolly LE, Miller LG, Friedland I, Dwyer JP | display-authors=3 | title=Once-Daily Plazomicin for Complicated Urinary Tract Infections | journal=New England Journal of Medicine | volume=380 | issue=8 | date=21 February 2019 | issn=0028-4793 | doi=10.1056/nejmoa1801467 | pages=729–740 | pmid=30786187 | doi-access=free }}
* {{lay source |template = cite web|vauthors = Dall C |url= http://www.cidrap.umn.edu/news-perspective/2019/02/plazomicin-tough-infections-tale-2-clinical-trials |title=
Plazomicin for tough infections: a tale of 2 clinical trials|date = February 21, 2019 |website = Center for Infectious Disease Research and Policy}}
</ref>

==History==
The drug was developed by the biotech company [[Achaogen]].  In 2012, the U.S. Food and Drug Administration granted [[Fast track (FDA)|fast track]] designation for the development and regulatory review of plazomicin.<ref>{{cite press release|title=Achaogen Announces Plazomicin Granted QIDP Designation by FDA|url=https://globenewswire.com/news-release/2015/01/08/695854/10114610/en/Achaogen-Announces-Plazomicin-Granted-QIDP-Designation-by-FDA.html|via=[[GlobeNewswire]]|publisher=[[Achaogen, Inc.]]|date=8 January 2015|access-date=27 April 2016|archive-date=28 April 2016|archive-url=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|url-status=live}}</ref> The FDA approved plazomicin for adults with complicated UTIs and limited or no alternative treatment options in 2018.<ref name="Zemdri label" /> Achaogen was unable to find a robust market for the drug, and declared bankruptcy a few months later.<ref>{{Cite news| url=https://www.nytimes.com/2019/12/25/health/antibiotics-new-resistance.html| title=Crisis Looms in Antibiotics as Drug Makers Go Bankrupt| newspaper=[[The New York Times]]| date=25 December 2019| vauthors=Jacobs A| access-date=12 July 2024| archive-date=1 February 2021| archive-url=https://web.archive.org/web/20210201230345/https://www.nytimes.com/2019/12/25/health/antibiotics-new-resistance.html| url-status=live}}</ref> As part of the bankruptcy process, the rights to plazomicin were sold to [[Cipla]] USA, who currently markets ZEMDRI.<ref>{{cite press release |title=Cipla acquires plazomicin - July 2019 |url=https://www.cipla.com/press-releases-statements/cipla-usa-furthers-amr-stewardship-acquisition-key-anti-infective |website=Cipla.com |access-date=12 September 2024 |language=en |url-status=live }}</ref> There is no generic plazomicin currently available in the US market.<ref>{{cite web |title=Generic Zemdri Availability |url=https://www.drugs.com/availability/generic-zemdri.html |website=Drugs.com |access-date=26 December 2019 |language=en |archive-date=6 August 2020 |archive-url=https://web.archive.org/web/20200806083922/https://www.drugs.com/availability/generic-zemdri.html |url-status=live }}</ref>

==Synthesis==
It is derived from [[sisomicin]] by appending a hydroxy-aminobutyric acid substituent at position 1 and a hydroxyethyl substituent at position 6'.<ref>{{cite journal | vauthors = 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 | display-authors = 6 | title = Synthesis and spectrum of the neoglycoside ACHN-490 | journal = Antimicrobial Agents and Chemotherapy | volume = 54 | issue = 11 | pages = 4636–4642 | date = November 2010 | pmid = 20805391 | pmc = 2976124 | doi = 10.1128/AAC.00572-10 }}</ref><ref name="Zhanel">{{cite journal | vauthors = Zhanel GG, Lawson CD, Zelenitsky S, Findlay B, Schweizer F, Adam H, Walkty A, Rubinstein E, Gin AS, Hoban DJ, Lynch JP, Karlowsky JA | display-authors = 6 | title = Comparison of the next-generation aminoglycoside plazomicin to gentamicin, tobramycin and amikacin | journal = Expert Review of Anti-Infective Therapy | volume = 10 | issue = 4 | pages = 459–473 | date = April 2012 | pmid = 22512755 | doi = 10.1586/eri.12.25 | s2cid = 31496981 }}</ref> The latter makes it impervious to acetylation (deactivation) by Aminoglycoside Acetyltransferase 6'-N- Type Ib (AAC(6')-Ib), the most prevalent AAC enzyme.<ref>{{cite journal | vauthors = Cox G, Ejim L, Stogios PJ, Koteva K, Bordeleau E, Evdokimova E, Sieron AO, Savchenko A, Serio AW, Krause KM, Wright GD | display-authors = 6 | title = Plazomicin Retains Antibiotic Activity against Most Aminoglycoside Modifying Enzymes | journal = ACS Infectious Diseases | volume = 4 | issue = 6 | pages = 980–987 | date = June 2018 | pmid = 29634241 | pmc = 6167752 | doi = 10.1021/acsinfecdis.8b00001 }}</ref>

==Names==
Plazomicin is the [[international nonproprietary name]] (INN).<ref>{{cite journal | title = International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended INN: List 68 | journal = WHO Drug Information | volume = 26 | issue = 3 | date = September 2012 | url = https://www.who.int/medicines/publications/druginformation/issues/DrugInformation2012_Vol26-3/en/ | archive-url = https://web.archive.org/web/20141002045030/http://www.who.int/medicines/publications/druginformation/issues/DrugInformation2012_Vol26-3/en/ | url-status = dead | archive-date = 2 October 2014 | publisher = [[World Health Organization]] | access-date = 27 April 2016 | page = 314}}</ref>
{{Clear}}

==References==
{{reflist}}

==Further reading==
* {{cite web | title=FDA Briefing Information for the May 2, 2018 Meeting of the Antimicrobial Drugs Advisory Committee | url=https://www.fda.gov/media/113161/download | publisher=U.S. [[Food and Drug Administration]] | date=2 May 2018 | access-date=14 September 2019 | df=dmy-all | format=PDF }}
* {{cite web | title=Achaogen Briefing Information for the May 2, 2018 Meeting of the Antimicrobial Drugs Advisory Committee | url=https://www.fda.gov/media/113190/download | publisher=U.S. [[Food and Drug Administration]] | date=2 May 2018 | access-date=14 September 2019 | df=dmy-all | format=PDF }}
* {{cite web | title=Errata to the Achaogen Briefing Information for the May 2, 2018 Meeting of the Antimicrobial Drugs Advisory Committee | url=https://www.fda.gov/media/113196/download | publisher=U.S. [[Food and Drug Administration]] | date=2 May 2018 | access-date=14 September 2019 | df=dmy-all | format=PDF }}

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[[Category:Aminoglycoside antibiotics]]
[[Category:World Health Organization essential medicines]]
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