Repository logo
 
Publication

Imipenem-Relebactam Susceptibility in Enterobacterales Isolates Recovered from ICU Patients from Spain and Portugal (SUPERIOR and STEP Studies)

2022Journal article Open access
Simple item page
dc.contributor.authorHernández-García, M
dc.contributor.authorGarcía-Castillo, M
dc.contributor.authorBou, G
dc.contributor.authorCercenado, E
dc.contributor.authorDelgado-Valverde, M
dc.contributor.authorOliver, A
dc.contributor.authorPitart, C
dc.contributor.authorRodríguez-Lozano, J
dc.contributor.authorTormo, N
dc.contributor.authorMelo-Cristino, J
dc.contributor.authorPinto, MF
dc.contributor.authorGonçalves, E
dc.contributor.authorAlves, V
dc.contributor.authorVieira, AR
dc.contributor.authorRamalheira, E
dc.contributor.authorSancho, L
dc.contributor.authorDiogo, J
dc.contributor.authorFerreira, R
dc.contributor.authorCruz, H
dc.contributor.authorChaves, C
dc.contributor.authorDuarte, J
dc.contributor.authorPássaro, L
dc.contributor.authorDíaz-Regañón, J
dc.contributor.authorCantón, R
dc.date.accessioned2023-04-13T14:20:38Z
dc.date.available2023-04-13T14:20:38Z
dc.date.issued2022
dc.description.abstractImipenem-relebactam is a novel β-lactam-β-lactamase inhibitor combination. We evaluated the in vitro activity of imipenem-relebactam and comparators against Enterobacterales clinical isolates recovered in 8 Spanish and 11 Portuguese intensive care units (ICUs) (SUPERIOR, 2016-2017; STEP, 2017-2018). Overall, 747 Enterobacterales isolates (378 Escherichia coli, 252 Klebsiella spp., 64 Enterobacter spp., and 53 other species) were prospectively collected from ICU patients with complicated intraabdominal (cIAI), complicated urinary tract (cUTI), and lower respiratory tract (LRTI) infections. MICs were determined (ISO-broth microdilution), and whole-genome sequencing (WGS) was performed in a subset of isolates displaying susceptible and resistant imipenem-relebactam MICs. Imipenem-relebactam (98.7% susceptible) showed similar activity to ceftazidime-avibactam (99.5% susceptible) and higher than ceftolozane-tazobactam (86.9% susceptible). Imipenem-relebactam was inactive against 1.3% (10/747) isolates, all of them due to carbapenemase production (9 K. pneumoniae and 1 E. cloacae). Imipenem-relebactam was active against 100% of extended-spectrum β-lactamase (ESBL)-E. coli and ESBL-Klebsiella spp. isolates and 80.4% of carbapenemase-Klebsiella spp. producers. Carbapenemase genes were confirmed by WGS in 41 Klebsiella spp.: OXA-48 (20/41), KPC-3 (14/41), OXA-181 (4/41), NDM-1 (1/41), OXA-48 + VIM-2 (1/41), and KPC-3 + VIM-2 (1/41). In Klebsiella spp. isolates, relebactam restored imipenem susceptibility in all KPC-3 producers, and resistant isolates (7/41) were mostly OXA-48 + CTX-M-15-K. pneumoniae high-risk clones (7/9). Intercountry differences were detected as follows: OXA-48 (17/21) was dominant in Spain, unlike KPC-3 (14/15) in Portugal. Imipenem-relebactam was 100% active against CTX-M-15-ST131-H30Rx-E. coli high-risk clone, predominant in both countries. Our results depict the potential role of imipenem-relebactam in ICU patients with cIAIs, cUTIs, and LRTIs due to wild-type ESBL- and carbapenemase-producing Enterobacterales, particularly KPC producers. IMPORTANCE We comparatively evaluate the in vitro activity of a drug combination consisting of a carbapenem (imipenem) and a novel inhibitor of beta-lactamases (relebactam), a mechanism that destroys beta-lactam antibiotics. We assess the activity against a collection of Enterobacterales clinical isolates recovered from difficult-to-treat infections in patients admitted to different intensive care units in Portugal and Spain. Imipenem-relebactam shows excellent activity in avoiding common resistance mechanisms in this setting, such as extended-spectrum beta-lactamases and carbapenemases widely distributed, including KPCs. We show few resistant isolates (<2%). Molecular characterization by whole-genome sequencing shows that most of the resistant isolates produced specific carbapenemase, such as OXA-48 or metalo-betalactamases. Our study updates the activity of imipenem-relebactam in light of current epidemiology in a hospital setting in which the use of this combination is needed due to the presence of infections due to multidrug-resistant isolates.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationMicrobiol Spectr . 2022 Oct 26;10(5):e0292722.pt_PT
dc.identifier.doi10.1128/spectrum.02927-22pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.17/4491
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherAmerican Society of Microbiologypt_PT
dc.subjectAnti-Bacterial Agents / pharmacologypt_PT
dc.subjectDrug Combinationspt_PT
dc.subjectEscherichia coli* / geneticspt_PT
dc.subjectImipenem / pharmacologypt_PT
dc.subjectIntensive Care Unitspt_PT
dc.subjectKlebsiella pneumoniae / geneticspt_PT
dc.subjectMicrobial Sensitivity Testspt_PT
dc.subjectTazobactam / pharmacologypt_PT
dc.subjectbeta-Lactamase Inhibitors* / pharmacologypt_PT
dc.subjectbeta-Lactamases / geneticspt_PT
dc.subjectPortugalpt_PT
dc.subjectSpainpt_PT
dc.subjectHDE PAT CLINpt_PT
dc.titleImipenem-Relebactam Susceptibility in Enterobacterales Isolates Recovered from ICU Patients from Spain and Portugal (SUPERIOR and STEP Studies)pt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue5pt_PT
oaire.citation.startPagee0292722pt_PT
oaire.citation.titleMicrobiology Spectrumpt_PT
oaire.citation.volume10pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

Files

License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

PAT CLIN - Artigos