Molecular Epidemiology of Global Carbapenemase-Producing Citrobacter spp. (2015-2017).

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 bla IMP-8 from Taiwan and bla KPC-2 from the United States, and ST22 was linked with bla KPC-2 from Colombia and bla VIM-1 from Italy. C. portucalensis consisted mainly of two clones: ST493 with bla IMP-4 which was limited to Australia, and ST545 with bla VIM-31 which was limited to Turkey. Class I integron (In916) with bla VIM-1 was circulating between multiple sequence types (STs) in Italy, Poland, and Portugal. In73 with bla IMP-8 was circulating between various STs in Taiwan, while In809 with bla IMP-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 hospital-acquired 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 bla IMP-8 from Taiwan and bla KPC-2 from the United States, and ST22 with bla KPC-2 from Colombia and bla VIM-1 from Italy. As for C. portucalensis , the dominant clones consisted of ST493 with bla IMP-4 from Australia and ST545 with bla VIM-31 from Turkey.