Carbapenem-Resistant Klebsiella aerogenes Clinical Isolates from a Teaching Hospital in Southwestern China: Detailed Molecular Epidemiology, Resistance Determinants, Risk Factors and Clinical Outcomes

Abstract

De-Yu Ma, 1,* Han-Yu Huang, 2,* Hua Zou, 1 Meng-Lu Wu, 1 Qiu-Xia Lin, 1 Bo Liu, 3 Shi-Feng Huang 1 1Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Radiology, Chongqing Health Center for Women and Children, Chongqing, People’s Republic of China; 3Department of Burn and Plastic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bo LiuDepartment of Burn and Plastic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China, No. 1 Friendship Road, Yuzhong District, Chongqing 400016, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected] Shi-Feng HuangDepartment of Clinical Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China, No. 1 Friendship Road, Yuzhong District, Chongqing 400016, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected]: 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 blaNDM-1, 1 (2.8%) harboring blaKPC-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 blaNDM-1, blaCTX-M-15, blaEBC, blaACC, 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, blaNDM-1, blaKPC-2, porins, efflux pumps

Keywords

• case-control study
• blandm-1
• blakpc-2
• porins
• efflux pumps