Cargando…

1348. In vitro Activity of Plazomicin, a Next-Generation Aminoglycoside, Against Carbapenemase-Producing Klebsiella pneumoniae

BACKGROUND: Plazomicin is a next-generation aminoglycoside with in vitro activity against multidrug-resistant Gram-negative species, including carbapenem-resistant isolates. The Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE) is a federally funded, p...

Descripción completa

Detalles Bibliográficos
Autores principales: Jacobs, Michael R, Good, Caryn E, Abdelhamed, Ayman M, Rhoads, Daniel D, Hujer, Kristine M, Hujer, Andrea M, Rudin, Susan D, Domitrovic, T Nicholas, Connolly, Lynn, Krause, Kevin M, Richter, Sandra S, Van Duin, David, Kreiswirth, Barry N, Bonomo, Robert A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6254231/
http://dx.doi.org/10.1093/ofid/ofy210.1179
_version_ 1783373677190971392
author Jacobs, Michael R
Good, Caryn E
Abdelhamed, Ayman M
Rhoads, Daniel D
Hujer, Kristine M
Hujer, Andrea M
Rudin, Susan D
Domitrovic, T Nicholas
Connolly, Lynn
Krause, Kevin M
Richter, Sandra S
Van Duin, David
Kreiswirth, Barry N
Bonomo, Robert A
author_facet Jacobs, Michael R
Good, Caryn E
Abdelhamed, Ayman M
Rhoads, Daniel D
Hujer, Kristine M
Hujer, Andrea M
Rudin, Susan D
Domitrovic, T Nicholas
Connolly, Lynn
Krause, Kevin M
Richter, Sandra S
Van Duin, David
Kreiswirth, Barry N
Bonomo, Robert A
author_sort Jacobs, Michael R
collection PubMed
description BACKGROUND: Plazomicin is a next-generation aminoglycoside with in vitro activity against multidrug-resistant Gram-negative species, including carbapenem-resistant isolates. The Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE) is a federally funded, prospective multicenter consortium of 20 hospitals from nine US healthcare systems to track carbapenem-resistant Enterobacteriaceae. METHODS: Minimum inhibitory concentrations (MICs) of plazomicin were determined by broth microdilution according to current CLSI guidelines against a collection of 697 carbapenem-resistant Klebsiella pneumoniae with defined carbapenem resistance mechanisms, including KPC and OXA carbapenemases. Isolates were submitted by participating CRACKLE centers. RESULTS: Carbapenemases present in study isolates included KPC-2 (n = 323), KPC-3 (n = 364), KPC-4 (n = 2), OXA-48 like (n = 7), and NDM (n = 1). Plazomicin MICs ranged from ≤0.12 to >32 mg/L, with MIC50 and MIC90 values of 0.25 and 1 mg/L, respectively (figure). MICs of 689 (98.8%) isolates were ≤4 mg/L, while MICs of the remaining eight isolates were >32 mg/L. Plazomicin MICs were related to specific carbapenemases present in isolates: of eight isolates with MICs >32 mg/L, seven contained OXA-48 like and one contained KPC-3, suggesting that these isolates possess an aminoglycoside-resistance mechanism on the same plasmid as their carbapenemase gene, such as a 16S ribosomal RNA methyltransferase, against which plazomicin is not active. CONCLUSION: Plazomicin has good in vitro potency against a collection of carbapenemase-producing K. pneumoniae, with MIC90 value of 1 mg/L and MICs of ≤4 mg/L for 98.9% of isolates. [Image: see text] DISCLOSURES: M. R. Jacobs, Achaogen: Investigator, Research grant. Shionogi: Investigator, Research grant. L. Connolly, Achaogen, Inc.: Consultant, Consulting fee. K. M. Krause, Achaogen: Employee, Salary. S. S. Richter, bioMerieux: Grant Investigator, Research grant. BD Diagnostics: Grant Investigator, Research grant. Roche: Grant Investigator, Research grant. Hologic: Grant Investigator, Research grant. Diasorin: Grant Investigator, Research grant. Accelerate: Grant Investigator, Research grant. Biofire: Grant Investigator, Research grant. D. Van Duin, achaogen: Scientific Advisor, Consulting fee. shionogi: Scientific Advisor, Consulting fee. Allergan: Scientific Advisor, Consulting fee. Astellas: Scientific Advisor, Consulting fee. Neumedicine: Scientific Advisor, Consulting fee. Roche: Scientific Advisor, Consulting fee. T2 Biosystems: Scientific Advisor, Consulting fee.
format Online
Article
Text
id pubmed-6254231
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-62542312018-11-28 1348. In vitro Activity of Plazomicin, a Next-Generation Aminoglycoside, Against Carbapenemase-Producing Klebsiella pneumoniae Jacobs, Michael R Good, Caryn E Abdelhamed, Ayman M Rhoads, Daniel D Hujer, Kristine M Hujer, Andrea M Rudin, Susan D Domitrovic, T Nicholas Connolly, Lynn Krause, Kevin M Richter, Sandra S Van Duin, David Kreiswirth, Barry N Bonomo, Robert A Open Forum Infect Dis Abstracts BACKGROUND: Plazomicin is a next-generation aminoglycoside with in vitro activity against multidrug-resistant Gram-negative species, including carbapenem-resistant isolates. The Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE) is a federally funded, prospective multicenter consortium of 20 hospitals from nine US healthcare systems to track carbapenem-resistant Enterobacteriaceae. METHODS: Minimum inhibitory concentrations (MICs) of plazomicin were determined by broth microdilution according to current CLSI guidelines against a collection of 697 carbapenem-resistant Klebsiella pneumoniae with defined carbapenem resistance mechanisms, including KPC and OXA carbapenemases. Isolates were submitted by participating CRACKLE centers. RESULTS: Carbapenemases present in study isolates included KPC-2 (n = 323), KPC-3 (n = 364), KPC-4 (n = 2), OXA-48 like (n = 7), and NDM (n = 1). Plazomicin MICs ranged from ≤0.12 to >32 mg/L, with MIC50 and MIC90 values of 0.25 and 1 mg/L, respectively (figure). MICs of 689 (98.8%) isolates were ≤4 mg/L, while MICs of the remaining eight isolates were >32 mg/L. Plazomicin MICs were related to specific carbapenemases present in isolates: of eight isolates with MICs >32 mg/L, seven contained OXA-48 like and one contained KPC-3, suggesting that these isolates possess an aminoglycoside-resistance mechanism on the same plasmid as their carbapenemase gene, such as a 16S ribosomal RNA methyltransferase, against which plazomicin is not active. CONCLUSION: Plazomicin has good in vitro potency against a collection of carbapenemase-producing K. pneumoniae, with MIC90 value of 1 mg/L and MICs of ≤4 mg/L for 98.9% of isolates. [Image: see text] DISCLOSURES: M. R. Jacobs, Achaogen: Investigator, Research grant. Shionogi: Investigator, Research grant. L. Connolly, Achaogen, Inc.: Consultant, Consulting fee. K. M. Krause, Achaogen: Employee, Salary. S. S. Richter, bioMerieux: Grant Investigator, Research grant. BD Diagnostics: Grant Investigator, Research grant. Roche: Grant Investigator, Research grant. Hologic: Grant Investigator, Research grant. Diasorin: Grant Investigator, Research grant. Accelerate: Grant Investigator, Research grant. Biofire: Grant Investigator, Research grant. D. Van Duin, achaogen: Scientific Advisor, Consulting fee. shionogi: Scientific Advisor, Consulting fee. Allergan: Scientific Advisor, Consulting fee. Astellas: Scientific Advisor, Consulting fee. Neumedicine: Scientific Advisor, Consulting fee. Roche: Scientific Advisor, Consulting fee. T2 Biosystems: Scientific Advisor, Consulting fee. Oxford University Press 2018-11-26 /pmc/articles/PMC6254231/ http://dx.doi.org/10.1093/ofid/ofy210.1179 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Abstracts
Jacobs, Michael R
Good, Caryn E
Abdelhamed, Ayman M
Rhoads, Daniel D
Hujer, Kristine M
Hujer, Andrea M
Rudin, Susan D
Domitrovic, T Nicholas
Connolly, Lynn
Krause, Kevin M
Richter, Sandra S
Van Duin, David
Kreiswirth, Barry N
Bonomo, Robert A
1348. In vitro Activity of Plazomicin, a Next-Generation Aminoglycoside, Against Carbapenemase-Producing Klebsiella pneumoniae
title 1348. In vitro Activity of Plazomicin, a Next-Generation Aminoglycoside, Against Carbapenemase-Producing Klebsiella pneumoniae
title_full 1348. In vitro Activity of Plazomicin, a Next-Generation Aminoglycoside, Against Carbapenemase-Producing Klebsiella pneumoniae
title_fullStr 1348. In vitro Activity of Plazomicin, a Next-Generation Aminoglycoside, Against Carbapenemase-Producing Klebsiella pneumoniae
title_full_unstemmed 1348. In vitro Activity of Plazomicin, a Next-Generation Aminoglycoside, Against Carbapenemase-Producing Klebsiella pneumoniae
title_short 1348. In vitro Activity of Plazomicin, a Next-Generation Aminoglycoside, Against Carbapenemase-Producing Klebsiella pneumoniae
title_sort 1348. in vitro activity of plazomicin, a next-generation aminoglycoside, against carbapenemase-producing klebsiella pneumoniae
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6254231/
http://dx.doi.org/10.1093/ofid/ofy210.1179
work_keys_str_mv AT jacobsmichaelr 1348invitroactivityofplazomicinanextgenerationaminoglycosideagainstcarbapenemaseproducingklebsiellapneumoniae
AT goodcaryne 1348invitroactivityofplazomicinanextgenerationaminoglycosideagainstcarbapenemaseproducingklebsiellapneumoniae
AT abdelhamedaymanm 1348invitroactivityofplazomicinanextgenerationaminoglycosideagainstcarbapenemaseproducingklebsiellapneumoniae
AT rhoadsdanield 1348invitroactivityofplazomicinanextgenerationaminoglycosideagainstcarbapenemaseproducingklebsiellapneumoniae
AT hujerkristinem 1348invitroactivityofplazomicinanextgenerationaminoglycosideagainstcarbapenemaseproducingklebsiellapneumoniae
AT hujerandream 1348invitroactivityofplazomicinanextgenerationaminoglycosideagainstcarbapenemaseproducingklebsiellapneumoniae
AT rudinsusand 1348invitroactivityofplazomicinanextgenerationaminoglycosideagainstcarbapenemaseproducingklebsiellapneumoniae
AT domitrovictnicholas 1348invitroactivityofplazomicinanextgenerationaminoglycosideagainstcarbapenemaseproducingklebsiellapneumoniae
AT connollylynn 1348invitroactivityofplazomicinanextgenerationaminoglycosideagainstcarbapenemaseproducingklebsiellapneumoniae
AT krausekevinm 1348invitroactivityofplazomicinanextgenerationaminoglycosideagainstcarbapenemaseproducingklebsiellapneumoniae
AT richtersandras 1348invitroactivityofplazomicinanextgenerationaminoglycosideagainstcarbapenemaseproducingklebsiellapneumoniae
AT vanduindavid 1348invitroactivityofplazomicinanextgenerationaminoglycosideagainstcarbapenemaseproducingklebsiellapneumoniae
AT kreiswirthbarryn 1348invitroactivityofplazomicinanextgenerationaminoglycosideagainstcarbapenemaseproducingklebsiellapneumoniae
AT bonomoroberta 1348invitroactivityofplazomicinanextgenerationaminoglycosideagainstcarbapenemaseproducingklebsiellapneumoniae
AT 1348invitroactivityofplazomicinanextgenerationaminoglycosideagainstcarbapenemaseproducingklebsiellapneumoniae