Emergence and characterization of tigecycline resistance in multidrug-resistant Klebsiella pneumoniae isolates from blood samples of patients in intensive care units in northern China.
Serious infections in intensive care unit patients caused by multidrug-resistant (MDR) Klebsiella pneumoniae represent a major threat worldwide owing to increased mortality and limited treatment options. With the application of tigecycline for MDR pathogens, tigecycline-non-susceptible K. pneumoniae isolates have recently emerged in China. To identify the susceptibility profile of MDR K. pneumoniae to tigecycline and evaluate the molecular characterization of tigecycline resistance, 214 MDR K. pneumoniae isolates were collected from blood samples of patients in intensive care units. MICs and clonal relatedness were determined by standard broth microdilution and multilocus sequence typing, respectively. Expression levels of efflux pumps and their global regulators were examined using real-time PCR. Mutations of local repressor were identified by PCR and sequencing. Our results show that the tigecycline resistance rate of 214 MDR K. pneumoniae isolates was 6.07 %. ST11 was the predominant clone type of tigecycline-non-susceptible K. pneumoniae isolates. Expression of efflux pump AcrB and global regulator RamA correlated with tigecycline MICs (AcrB: x2=8.91, P=0.03; RamA: x2=13.91, P<0.01), and mean expression levels of AcrB for the MICs ≥4 mg l-1 were significantly higher than MICs ≤2 mg l-1 (t=2.48, P=0.029). In addition, one tigecycline-resistant isolate harboured a deletion mutation in the ramR gene. These data indicated a linear correlative trend for overexpression of the AcrB and the tigecycline MICs resulting from the upregulation of RamA. The emergence of molecular type ST11 of MDR K. pneumoniae isolates should be monitored to identify factors that contribute to tigecycline resistance in intensive care units.
Department of Clinical Laboratory, First Affiliated Hospital of Dalian Medical University, Dalian 116011, PR China.
Hui
H
Xu
Institute for Chronic and Non-communicable Disease Prevention and Control, Dalian Center for Disease Prevention and Control, Dalian 116021, PR China.
Yiheng
Y
Zhou
Department of Clinical Nutrition, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, PR China.
Xingyue
X
Zhai
Department of Biotechnology, Dalian Medical University, Dalian 116044, PR China.
Zemin
Z
Du
Department of Biotechnology, Dalian Medical University, Dalian 116044, PR China.
Hao
H
Wu
Department of Biotechnology, Dalian Medical University, Dalian 116044, PR China.
Yujia
Y
Han
Department of Biotechnology, Dalian Medical University, Dalian 116044, PR China.
Chunxiu
C
Huo
Department of Biotechnology, Dalian Medical University, Dalian 116044, PR China.
Yang
Y
Chen
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016470:Bacteremia / Q000382:microbiology*; D002681:China; D004252:DNA Mutational Analysis; D024901:Drug Resistance, Multiple, Bacterial; D020869:Gene Expression Profiling; D005809:Genes, Regulator; D006801:Humans; D007362:Intensive Care Units; D007710:Klebsiella Infections / Q000382:microbiology*; D007711:Klebsiella pneumoniae / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D026901:Membrane Transport Proteins / Q000235:genetics; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D058885:Multilocus Sequence Typing; D060888:Real-Time Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D000078304:Tigecycline
D000900:Anti-Bacterial Agents; D026901:Membrane Transport Proteins; D008911:Minocycline; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D000078304:Tigecycline