Activity of meropenem/vaborbactam against international carbapenem-resistant Escherichia coli isolates in relation to clonal background, resistance genes, resistance to comparators and region

Abstract

Objectives: Carbapenem resistance has emerged inEscherichia coli, including sequence type 131 (ST131) and its fluoroquinolone-resistant H30R subclone, the leading cause of extraintestinal E. coli infections globally. Meropenem/vaborbactam (MVB) is a recently approved carbapenem/β-lactamase inhibitor combination with broad-spectrum inhibition of β-lactamases, including serine carbapenemases. The activity of MVB against carbapenem-resistant (CR) E. coli infections in relation to phylogenetic background, resistance genotype and geographical region is unknown.

Methods: We characterised 140 contemporary CR clinicalE. coli isolates from 17 non-US countries (2003-2017) for phylogroup, clonal group (including ST131, H30R and the CTX-M-15-associated H30Rx subset), relevant β-lactamase genes, and broth microdilution MICs for MVB and 11 comparators.

Results: Overall, MVB was moderately active (66% susceptible), more so than all comparators except tigecycline and amikacin (100% and 74% susceptible, respectively). Most MVB-non-susceptible isolates carried metallo-β-lactamase or OXA-48 resistance genes. MVB's activity varied significantly in relation to phylogroup, clonal background, resistance genotype and global region: it was greatest among phylogroup F, ST131-H30R, H30Rx, Klebsiella pneumoniae carbapenemase (KPC)-positive and Latin American isolates, and lowest among phylogroup B1, metallo-β-lactamase gene-containing and Asia-West Pacific region isolates. Enhancement of meropenem's activity by vaborbactam was most evident for isolates from phylogroups B2, C and D, and those containing KPC. MVB retained appreciable (albeit somewhat reduced) activity against isolates resistant to comparator agents.

Conclusion: MVB should be useful for treating international CRE. coli infections, largely independent of other resistance phenotypes, although this likely will vary with the local prevalence of specific E. coli lineages and carbapenem resistance mechanisms.

Keywords: Carbapenem resistance; Escherichia coli; Klebsiella pneumoniae carbapenemase; Meropenem/vaborbactam; New Delhi metallo-β-lactamase; ST131.