Activity of imipenem/relebactam against a Spanish nationwide collection of carbapenemase-producing Enterobacterales

Abstract

Background Imipenem/relebactam is a novel carbapenem/β-lactamase inhibitor combination, developed to act against carbapenemase-producing Enterobacterales (CPE). Objectives To assess the in vitro activity of imipenem/relebactam against a Spanish nationwide collection of CPE by testing the susceptibility of these isolates to 16 widely used antimicrobials and to determine the underlying β-lactam resistance mechanisms involved and the molecular epidemiology of carbapenemases in Spain. Materials and methods Clinical CPE isolates (n = 401) collected for 2 months from 24 hospitals in Spain were tested. MIC50, MIC90 and susceptibility/resistance rates were interpreted in accordance with the EUCAST guidelines. β-Lactam resistance mechanisms and molecular epidemiology were characterized by WGS. Results For all isolates, high rates of susceptibility to colistin (86.5%; MIC50/90 = 0.12/8 mg/L), imipenem/relebactam (85.8%; MIC50/90 = 0.5/4 mg/L) and ceftazidime/avibactam (83.8%, MIC50/90 = 1/≥256 mg/L) were observed. The subgroups of isolates producing OXA-48-like (n = 305, 75.1%) and KPC-like enzymes (n = 44, 10.8%) were highly susceptible to ceftazidime/avibactam (97.7%, MIC50/90 = 1/2 mg/L) and imipenem/relebactam (100.0%, MIC50/90 = ≤0.25/1 mg/L), respectively. The most widely disseminated high-risk clones of carbapenemase-producing Klebsiella pneumoniae across Spain were found to be ST11, ST147, ST392 and ST15 (mostly associated with OXA-48) and ST258/512 (in all cases producing KPC). Conclusions Imipenem/relebactam, colistin and ceftazidime/avibactam were the most active antimicrobials against all CPEs. Imipenem/relebactam is a valuable addition to the antimicrobial arsenal used in the fight against CPE, particularly against KPC-producing isolates, which in all cases were susceptible to this combination.

CARB-ES-19 Multicenter Study of Carbapenemase-Producing Klebsiella pneumoniae and Escherichia coli From All Spanish Provinces Reveals Interregional Spread of High-Risk Clones Such as ST307/OXA-48 and ST512/KPC-3

“…Our results confirm previous reports of the preponderance of OXA-48 carbapenemase in Spain (detected in 82% of Spanish provinces; Oteo et al, 2015 ; Grundmann et al, 2017 ; Vázquez-Ucha et al, 2021 ). The bla OXA–505 gene (OXA-48 family, GenBank number: NG_049783) was detected in a carbapenem non-susceptible isolate with a positive colorimetric lacking other genes encoding carbapenemases, so it was included in the study despite the absence of published evidence on its carbapenemase activity.…”

“…Overall susceptibility to colistin and meropenem decreased from 95.5 to 81.3%, respectively, in 2013 (Oteo et al, 2015) to 90.5% and 52.3% in this study, due primarily to the rise in KPC and NDM. The rate of colistin resistance was lower than previously reported, associated with KPC-producers (Di Pilato et al, 2021) but was consistent with the rate reported in a recent Spanish study (Vázquez-Ucha et al, 2021).…”

“…Regarding the level of resistance to carbapenem antibiotics as the main target of carbapenemases, it should be noted that the susceptibility profile of meropenem and/or imipenem susceptibility with ertapenem resistance was frequently detected in this study. This profile was mainly due to the high prevalence of OXA-48 isolates, although it can also be found in VIM-1 producers ( Oteo et al, 2015 ; Vázquez-Ucha et al, 2021 ).…”

Characterization of Extensively Drug-Resistant (XDR) Carbapenemase-Producing Enterobacterales (CPE) in Canada from 2019 to 2020

“…The travel and medical history risk factors that we identified are consistent with those described in the literature for CPE acquisition in general ( 11 ). Our findings align with surveillance from Greece and Spain, which found that the activity of ceftazidime-avibactam was higher than that of imipenem/relebactam against Enterobacterales harboring OXA-48-type carbapenemases ( 12 , 13 ). Further, this report applies novel Canadian recommendations for the laboratory interpretation of XDR clinical isolates to national surveillance data ( 8 ).…”

A Study in a Regional Hospital of a Mid-Sized Spanish City Indicates a Major Increase in Infection/Colonization by Carbapenem-Resistant Bacteria, Coinciding with the COVID-19 Pandemic

“…The relationships between STs and carbapenemases were explored in the detected CPB, followed by a search for ST–carbapenemase combinations that have been reported in Spain for each CPB, highlighting isolates of: K. pneumoniae ST15-OXA-48 [ 20 , 21 ], ST258-KPC-3 [ 8 , 22 ], ST307-OXA-48 [ 23 , 24 ], and ST512-KPC-3 [ 23 , 25 , 26 , 27 ]; K. oxytoca ST36-VIM 1 [ 28 ]; E. coli ST58-OXA-48 [ 29 ]; E. cloacae ST114-OXA-48 [ 30 ]; A. baumannii ST1-OXA-23 [ 31 ]; and P. aeruginosa ST175-VIM-2 [ 32 , 33 ].…”