Methods: We performed a case-control study of patients with CREC (cases) and 3rd-generation cephalosporin-resistant E. cloacae (Ceph-R) (controls) collected at our hospital since 2010, matched by age, sex, and year of culture, to identify clinical and molecular factors associated with CREC. Isolate sensitivities were determined by Vitek2; genotyping was performed using multi-locus sequence typing (MLST). Select CREC and Ceph-R isolates underwent whole genome sequencing using Illumina HiSeq, and MLST, resistance gene, and plasmid types were extracted using SRST2.
Results: Clinical data were obtained from 68 cases and 68 matched controls. Patients were older (median age 59) and 66% were male. CREC was more likely than Ceph-R to occur >2 days after admission (82% versus 54%, p = 0.0004), and to be cultured from the respiratory tract compared to the blood or urine (overall p = 0.003). We typed 58 CREC and 48 Ceph-R isolates and identified 26 and 20 different STs, respectively. ST171 was the most common CREC ST (n=26) followed by ST78 (n=6) which was also the dominant Ceph-R ST (n=21). blaKPC-3 (n=30), blaKPC-2 (n=12), and blaKPC-4 (n=2) were the putative mechanisms of carbapenem resistance in CREC isolates. WGS analysis revealed a single blaKPC-3-harboring ST171 clone present since 2010, suggesting persistent colonizing or environmental reservoirs, whereas ST78 consisted of several clades. ST171 and ST78 occurred in both CREC and Ceph-R but did not share potential blaKPC-harboring plasmids.
Conclusion: CREC appeared to be due to both sporadic acquisition of blaKPC-encoding plasmids and spread of dominant clones ST171 and ST78. However, ST78 and ST171 also occurred among Ceph-R isolates, implicating a more complex dynamic of plasmid uptake and clonal expansion in this organism.
S. Sullivan, None
Z. Wang, None
S. Whittier, None
A. C. Uhlemann, None