Impact of Carbapenem Heteroresistance Among Multidrug-Resistant ESBL/AmpC-Producing Klebsiella pneumoniae Clinical Isolates on Antibiotic Treatment in Experimentally Infected Mice

Yilin Xiong,1,* Yuqiao Han,1,* Zinan Zhao,1,* Wenting Gao,2 Yong Ma,2 Shiyu Jiang,1 Mengyao Wang,1 Qingqing Zhang,3 Yun Zhou,4 Yang Chen1 1Department of Biotechnology, College of Basic Medical Sciences, Dalian Medical University, Dalian, People’s Republic of China; 2Institute of Genome Engineered Animal Models for Human Disease, Dalian Medical University, Dalian, People’s Republic of China; 3Laboratory of Pathogenic Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, People’s Republic of China; 4Department of Clinical Nutrition, Second Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yang ChenDepartment of Biotechnology, College of Basic Medical Sciences, Dalian Medical University, 9 West Section of Lvshun South Road, Dalian, 116044, People’s Republic of ChinaTel/Fax +86 411 86110350Email yangchen@dmu.edu.cnYun ZhouDepartment of Clinical Nutrition, Second Affiliated Hospital of Dalian Medical University, 467 Zhongshan Road, Dalian, 116023, People’s Republic of ChinaTel +86 411 84690722Fax +86 411 84672130Email dmu_yunzhou@yeah.netPurpose: Antibiotic resistance is a growing health crisis that is further complicated by treatment failures caused by bacteria that exhibit heterogeneous susceptibility to antibiotics. The aim of this study was to describe imipenem (IPM)-heteroresistant strains among multidrug-resistant (MDR) ESBL/AmpC-producing Klebsiella pneumoniae clinical isolates, investigate their molecular phenotypic characteristics, and elucidate the outcome of antibiotic treatment in mice infected with the heteroresistant isolates.Materials and Methods: Antimicrobial susceptibility of K. pneumoniae isolates was determined by the disk diffusion and E-test methods. Heteroresistance to IPM was confirmed by population analysis profile (PAP) assays. PCR and sequencing were employed to detect MDR determin