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

Background: Imipenem/relebactam is a novel carbapenem/b-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 beta-lactamresistance 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. b-Lactam resistance mechanisms and molecular epidemiology were characterized by WGS. Results: For all isolates, high rates of susceptibility to colistin (86.5%; MIC50/90 C = 0.12/8 mg/L), imipenem/relebactam (85.8%; MIC50/90 = 0.5/4 mg/L) and ceftazidime/avibactam (83.8%, MIC50/90 = 1/>= 256mg/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.

Automated summary

Imipenem/relebactam, colistin, and ceftazidime/avibactam were found to be the most active antimicrobials against carbapenemase-producing Enterobacterales in a Spanish nationwide collection. The most widely disseminated high-risk clones of these carbapenemase-producing Klebsiella pneumoniae in Spain were identified as ST11, ST147, ST392, ST15, and ST258/512. The combination of imipenem/relebactam was particularly effective against KPC-producing isolates.