Abstract:
The emergence of carbapenem resistance is a significant public health
concern. The rate of infections caused by carbapenemase-producing Citrobacter spp.,
particularly C. freundii, is increasing. Concomitantly, comprehensive global genomic
data on carbapenemase-producing Citrobacter spp. are scarce. We used short read
whole-genome sequencing to describe the molecular epidemiology and international
distribution of eighty-six carbapenemase-producing Citrobacter spp. obtained from two
surveillance programs (2015 to 17). The common carbapenemases were KPC-2 (26%),
VIM-1 (17%), IMP-4 (14%) and NDM-1 (10%). C. freundii and C. portucalensis were the
principal species. C. freundii consisted of multiple clones obtained mainly from
Colombia (with KPC-2), the United States (with KPC-2, -3), and Italy (with VIM-1). Two
dominant C. freundii clones were identified: ST98 was linked with blaIMP-8 from Taiwan
and blaKPC-2 from the United States, and ST22 was linked with blaKPC-2 from Colombia
and blaVIM-1 from Italy. C. portucalensis consisted mainly of two clones: ST493 with
blaIMP-4 which was limited to Australia, and ST545 with blaVIM-31 which was limited
to Turkey. Class I integron (In916) with blaVIM-1 was circulating between multiple
sequence types (STs) in Italy, Poland, and Portugal. In73 with blaIMP-8 was circulating
between various STs in Taiwan, while In809 with blaIMP-4 was circulating between different
STs in Australia. The global carbapenemase-producing Citrobacter spp. population
is dominated by diverse STs with different characteristics and varied geographical
distribution and thus requires continued monitoring. Ongoing genomic surveillance
should use methodologies able to distinguish between C. freundii and C. portucalensis.
IMPORTANCE Citrobacter spp. are gaining recognition as important causes of hospitalacquired
infections in humans. Among Citrobacter spp., carbapenemase-producing strains are cause of utmost concern to health care services globally due to their ability
to resist therapy with virtually any beta-lactam antibiotic. Here, we described the molecular
characteristics of a global collection of carbapenemase-producing Citrobacter
spp. C. freundii and C. portucalensis were the most common species among Citrobacter
spp. with carbapenemases from this survey. Importantly, C. portucalensis was misidentified
as C. freundii when using Vitek 2.0/ MALDI-TOF MS (matrix-assisted laser desorption/
ionization–time of flight mass spectrometry) phenotypic identification, which has
important implications for future surveys. Among C. freundii, we identified two dominant
clones: ST98 with blaIMP-8 from Taiwan and blaKPC-2 from the United States, and
ST22 with blaKPC-2 from Colombia and blaVIM-1 from Italy. As for C. portucalensis, the
dominant clones consisted of ST493 with blaIMP-4 from Australia and ST545 with blaVIM-31
from Turkey.
