Activity of meropenem/vaborbactam against international carbapenem-resistant Escherichia coli isolates in relation to clonal background, resistance genes, resistance to comparators and region. (March 2021)

• Record Type: Journal Article
• Authors: Johnston, Brian D.; Thuras, Paul; Porter, Stephen B.; Castanheira, Mariana; Johnson, James R.
• Is Part Of: Journal of global antimicrobial resistance. Volume 24(2021)
• Page Start: 190
• Page End: 197
• Publication Date: 2021-03
• Subjects: Escherichia coli -- Carbapenem resistance -- ST131 -- Meropenem/vaborbactam -- Klebsiella pneumoniae carbapenemase -- New Delhi metallo-β-lactamase; Drug resistance -- Periodicals; Drug resistance -- Periodicals; Drug resistance; Periodicals; 616.9041
• DOI: 10.1016/j.jgar.2020.12.017
• Languages: English
• ISSNs: 2213-7165

Abstract

Highlights: Meropenem/vaborbactam (MVB) is a recently approved carbapenem/β-lactamase inhibitor combination. Of the 12 tested agents, MVB exhibited the third highest percent susceptible (66%). Most MVB-resistant isolates carried metallo-β-lactamase or OXA-48 resistance genes. MVB's activity varied by phylogenetic/clonal group, resistance genotype and region. MVB retained appreciable activity against isolates co-resistant to comparator agents. Abstract: Objectives: Carbapenem resistance has emerged in Escherichia coli, including sequence type 131 (ST131) and its fluoroquinolone-resistant H 30R 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 clinical E. coli isolates from 17 non-US countries (2003–2017) for phylogroup, clonal group (including ST131, H 30R and the CTX-M-15-associated H 30Rx 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- H 30R, H 30Rx, 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 CR E. 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.