Purpose: Little is known about the epidemiology and carbapenem-resistance determinants of carbapenem-resistant K. aerogenes  (CRKA) isolated from a single medical center. The present study was initiated to characterize the molecular epidemiology and the carbapenem-resistance mechanisms of CRKA isolated during 2012– 2018 from a teaching hospital in southwest China, and to investigate the risk factors and clinical outcomes of CRKA infections as well.
Methods: Pulsed-field gel electrophoresis (PFGE) was employed for epidemiological analysis. PCR amplification and DNA sequencing were used to examine the antibiotic-resistance determinants. Plasmids were extracted and characterized by PCR-based replicon typing and conjugation assays. In order to further investigate the risk factors and clinical outcomes of CRKA infections, a retrospective case–control study was also performed.
Results: PFGE analysis showed 32 different PFGE patterns among the 36 non-duplicated CRKA strains collected. Most of the isolates harbored multi-drug resistance (MDR) genes, including 2 (5.6%) carrying bla _NDM-1, 1 (2.8%) harboring bla _KPC-2, 13 (36.1%) carrying ESBL genes, 23 (63.9%) carrying ampC genes, 34 (94.4%) carrying quinolone resistance determinants (QRD) genes and 9 (25%) carrying aminoglycoside resistance determinants (ARD) genes. The outer membrane porins, OmpE35 and OmpE36, were, respectively, lost in 4 and 2 isolates. The efflux pump inhibition experiments were positive in 25 (69.4%) of the CRKA strains. Multivariate analysis indicated that hypo-albuminaemia, invasive procedures, and carbapenem exposure were independent risk factors for acquiring CRKA infections.
Conclusion: No clonality relationship was identified among most of the 36 CRKA isolates. The over-expression of ESBLs and AmpC coupled with the efflux pumps contributed to carbapenem resistance in K. aerogenes . Additionally, this is the first report of CRKA isolate co-harboring bla _NDM-1, bla _CTX-M-15, bla _EBC, bla _ACC, acc (6ʹ)-Ib, armA, qnrD  and loss of OmpE36 in China. Hypo-albuminaemia, invasive procedures and carbapenem exposure were associated with acquisition of CRKA infections.
Keywords: case-control study, bla _NDM-1, bla _KPC-2, porins, efflux pumps