Abstract
The global spread of antimicrobial-resistant pathogens remains a major challenge in clinical practice. Among
these, carbapenem-resistant Enterobacterales (CRE) are of particular concern, with their prevalence increasing
markedly across Asia. In Japan, most CRE isolates produce imipenemase (IMP)-type metallo-β-lactamases
(MBLs). Moreover, many strains detected in western Japan carry pKPI-6–related plasmids and their derivatives
harboring blaIMP-6, which confer resistance to carbapenems but characteristically retain susceptibility to the
aminoglycoside amikacin. We conducted a 13-year surveillance study (2012–2024) of Escherichia coli isolates at
a mixed-care medical facility in northern Osaka Prefecture, primarily serving patients requiring chronic care.
Among 59 carbapenem-resistant E. coli strains identified, two exhibited resistance to both carbapenems and
amikacin. Both isolates carried blaIMP-6 and the aminoglycoside 6′-N-acetyltransferase (aac(6′)-Ib) genes with an aac(6′)-Ib variant associated with reduced amikacin resistance, arranged in tandem on the same plasmid. Furthermore,
one strain harbored the aac(6′)-Iae, which appears to represent a rarely documented occurrence in E. coli,
whereas the other carried aac(6′)-Ib-cr. Cloning experiments and minimum inhibitory concentrations (MICs) analyses
identified aac(6′)-Iae and aac(6′)-Ib-cr as the likely principal contributors to amikacin resistance in these
isolates, whereas the contribution of the aac(6′)-Ib(L119S) variant appeared limited. Genome database analysis
of IMP-type MBL-producing CRE prevalent in Japan suggested parallel dissemination of blaIMP and the aac(6′)-
Ib(L119S) variant, which may partly explain the high proportion of isolates that remain susceptible to amikacin.
Continued surveillance is warranted to monitor potential shifts in resistance profiles, including the emergence of
isolates with increased resistance to amikacin.
