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1595. Comparative In Vitro Activity of Imipenem–Relebactam Against Drug-Resistant Gram-Negative Isolates from Pediatric Patients
BACKGROUND: Drug resistance in Gram-negative bacteria is of particular concern in children. Relebactam, a novel diazabicyclooctane inhibitor, coupled with imipenem has broad-spectrum activity against β-lactamase producing organisms. Here, we compare the in vitro activity of imipenem-relebactam to 10...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6808878/ http://dx.doi.org/10.1093/ofid/ofz360.1459 |
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author | Banerjee, Dithi Harrison, Christopher J Pence, Morgan Selvarangan, Rangaraj |
author_facet | Banerjee, Dithi Harrison, Christopher J Pence, Morgan Selvarangan, Rangaraj |
author_sort | Banerjee, Dithi |
collection | PubMed |
description | BACKGROUND: Drug resistance in Gram-negative bacteria is of particular concern in children. Relebactam, a novel diazabicyclooctane inhibitor, coupled with imipenem has broad-spectrum activity against β-lactamase producing organisms. Here, we compare the in vitro activity of imipenem-relebactam to 10 standard comparator drugs against resistant Gram-negative isolates from two US pediatric hospitals. METHODS: We tested 100 isolates (50 per site) from pediatric clinical specimens tested during 2015–2017. All isolates were extended-spectrum cephalosporin-resistant (ESC-R); more than half were multidrug resistant (67%). Selected ESC-R isolates included Escherichia coli (90), Klebsiella pneumoniae (8), Klebsiella oxytoca (1), and Enterobacter cloacae (1) that were resistant or intermediate to ≥1 cephalosporins and/or aztreonam. A 0.5 McFarland suspension was prepared from colonies grown on blood agar plates (Thermo Scientific) at 35 ± 1°C for 18–24 hours. A final inoculum of 5 × 10(5) CFU/mL was prepared in Mueller–Hinton broth. Sensititre plates (Thermo Fisher Scientific) containing graded concentrations of imipenem/relebactam and 10 comparator drugs were inoculated and incubated at 35 ± 1°C for 18–24 hours. The minimum inhibitory concentration (MIC) was determined using the Sensititre Vizion system (Thermo Fisher Scientific) and endpoints were interpreted using CLSI (2019) breakpoint criteria, with the exception of colistin (EUCAST 2019). RESULTS: Selected ESC-R isolates had high rates of resistance to cephalosporins (64%–97%), aztreonam (80%), and levofloxacin (61%). All isolates were susceptible to imipenem/relebactam, imipenem and meropenem (MIC, ≤1 μg/mL for all). The imipenem/relebactam MIC(50) (0.06 μg/mL) and MIC(90) (0.12 μg/mL) values for ESC-R isolates were within one dilution of MICs of imipenem alone (0.12 μg/mL and 0.25 μg/mL). Among the comparators, colistin, amikacin, and piperacillin/tazobactam demonstrated comparable activities with 100%, 99%, and 94% susceptibilities, respectively. CONCLUSION: Meropenem, imipenem alone and in combination with relebactam exhibited 100% susceptibilities against ESC-R Enterobacteriaceae isolated from pediatric specimens, demonstrating the high potency of carbapenems. [Image: see text] DISCLOSURES: All authors: No reported disclosures. |
format | Online Article Text |
id | pubmed-6808878 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-68088782019-10-28 1595. Comparative In Vitro Activity of Imipenem–Relebactam Against Drug-Resistant Gram-Negative Isolates from Pediatric Patients Banerjee, Dithi Harrison, Christopher J Pence, Morgan Selvarangan, Rangaraj Open Forum Infect Dis Abstracts BACKGROUND: Drug resistance in Gram-negative bacteria is of particular concern in children. Relebactam, a novel diazabicyclooctane inhibitor, coupled with imipenem has broad-spectrum activity against β-lactamase producing organisms. Here, we compare the in vitro activity of imipenem-relebactam to 10 standard comparator drugs against resistant Gram-negative isolates from two US pediatric hospitals. METHODS: We tested 100 isolates (50 per site) from pediatric clinical specimens tested during 2015–2017. All isolates were extended-spectrum cephalosporin-resistant (ESC-R); more than half were multidrug resistant (67%). Selected ESC-R isolates included Escherichia coli (90), Klebsiella pneumoniae (8), Klebsiella oxytoca (1), and Enterobacter cloacae (1) that were resistant or intermediate to ≥1 cephalosporins and/or aztreonam. A 0.5 McFarland suspension was prepared from colonies grown on blood agar plates (Thermo Scientific) at 35 ± 1°C for 18–24 hours. A final inoculum of 5 × 10(5) CFU/mL was prepared in Mueller–Hinton broth. Sensititre plates (Thermo Fisher Scientific) containing graded concentrations of imipenem/relebactam and 10 comparator drugs were inoculated and incubated at 35 ± 1°C for 18–24 hours. The minimum inhibitory concentration (MIC) was determined using the Sensititre Vizion system (Thermo Fisher Scientific) and endpoints were interpreted using CLSI (2019) breakpoint criteria, with the exception of colistin (EUCAST 2019). RESULTS: Selected ESC-R isolates had high rates of resistance to cephalosporins (64%–97%), aztreonam (80%), and levofloxacin (61%). All isolates were susceptible to imipenem/relebactam, imipenem and meropenem (MIC, ≤1 μg/mL for all). The imipenem/relebactam MIC(50) (0.06 μg/mL) and MIC(90) (0.12 μg/mL) values for ESC-R isolates were within one dilution of MICs of imipenem alone (0.12 μg/mL and 0.25 μg/mL). Among the comparators, colistin, amikacin, and piperacillin/tazobactam demonstrated comparable activities with 100%, 99%, and 94% susceptibilities, respectively. CONCLUSION: Meropenem, imipenem alone and in combination with relebactam exhibited 100% susceptibilities against ESC-R Enterobacteriaceae isolated from pediatric specimens, demonstrating the high potency of carbapenems. [Image: see text] DISCLOSURES: All authors: No reported disclosures. Oxford University Press 2019-10-23 /pmc/articles/PMC6808878/ http://dx.doi.org/10.1093/ofid/ofz360.1459 Text en © The Author(s) 2019. 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 Banerjee, Dithi Harrison, Christopher J Pence, Morgan Selvarangan, Rangaraj 1595. Comparative In Vitro Activity of Imipenem–Relebactam Against Drug-Resistant Gram-Negative Isolates from Pediatric Patients |
title | 1595. Comparative In Vitro Activity of Imipenem–Relebactam Against Drug-Resistant Gram-Negative Isolates from Pediatric Patients |
title_full | 1595. Comparative In Vitro Activity of Imipenem–Relebactam Against Drug-Resistant Gram-Negative Isolates from Pediatric Patients |
title_fullStr | 1595. Comparative In Vitro Activity of Imipenem–Relebactam Against Drug-Resistant Gram-Negative Isolates from Pediatric Patients |
title_full_unstemmed | 1595. Comparative In Vitro Activity of Imipenem–Relebactam Against Drug-Resistant Gram-Negative Isolates from Pediatric Patients |
title_short | 1595. Comparative In Vitro Activity of Imipenem–Relebactam Against Drug-Resistant Gram-Negative Isolates from Pediatric Patients |
title_sort | 1595. comparative in vitro activity of imipenem–relebactam against drug-resistant gram-negative isolates from pediatric patients |
topic | Abstracts |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6808878/ http://dx.doi.org/10.1093/ofid/ofz360.1459 |
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