Clinical and genomic characteristics of IMP-producing Enterobacter cloacae complex and Klebsiella pneumoniae

Abstract

Carbapenemase-producing Enterobacterales (CPEs) are one of the top priority antimicrobial-resistant pathogens. Among CPEs, those producing acquired metallo-β-lactamases (MBLs) are considered particularly problematic as few agents are active against them. Imipenemase (IMP) is the most frequently encountered acquired MBL in Japan, but comprehensive assessment of clinical and microbiological features of IMP-producing Enterobacterales infection remains scarce. Here, we retrospectively evaluated 62 patients who were hospitalized at a university hospital in Japan and had IMP-producing Enterobacterales from a clinical culture. The isolates were either Enterobacter cloacae complex or Klebsiella pneumoniae, and most of them were isolated from sputum. The majority of K. pneumoniae, but not E. cloacae complex isolates, were susceptible to aztreonam. Sequence type (ST) 78 and ST517 were prevalent for E. cloacae complex and K. pneumoniae, respectively, and all isolates carried bla_IMP-1. Twenty-four of the patients were deemed infected with IMP-producing Enterobacterales. Among the infected patients, therapy varied and largely consisted of conventional β-lactam agents, fluoroquinolones, or combinations. Three (13%), five (21%), and nine (38%) of them died by days 14, 30, and 90, respectively. While incremental mortality over 90 days was observed in association with underlying comorbidities, active conventional treatment options were available for most patients with IMP-producing Enterobacterales infections, distinguishing them from more multidrug-resistant CPE infections associated with globally common MBLs, such as New Delhi metallo-β-lactamase (NDM) and Verona integron-encoded metallo-β-lactamase (VIM).

Keywords: carbapenemase-producing Enterobacterales; clinical outcome; genome epidemiology; metallo-beta-lactamase.

Fig 1

Phylogenetic tree of IMP-producing Enterobacter hormaechei ST78 and ST2480 isolates. cgSNP analysis showed that Enterobacter hormaechei ST78 isolates (n = 26) and its single-locus variant, ST2480 (n = 1), possessed between 1 and 342 cgSNPs. The strains were classified into four clusters and five singletons displaying cgSNPs equal to or fewer than 10.

Fig 2

Phylogenetic tree of IMP-producing Klebsiella pneumoniae ST517 isolates. cgSNP analysis showed that Klebsiella pneumoniae ST517 isolates (n = 17) had between 1 and 161 cgSNPs. The strains were classified into three clusters and seven singletons displaying cgSNPs equal to or fewer than 10.

Fig 3

IncFII plasmids carrying bla_IMP-1. The linear genomic maps represent complete plasmid sequences from Enterobacter hormaechei ST141 (FUJH0016), the plasmids from representative strains for Klebsiella pneumoniae ST517 (FUJH0032), ST76 (FUJH0043), and ST461 (FUJH0050) are given from top to bottom. bla_IMP-1 is indicated in red.