| Autor: |
Wu Y; Department of Clinical Laboratory, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China., Yang X; Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Konggrid.35030.35, Kowloon, Hong Kong., Liu C; Department of Clinical Laboratory, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China., Zhang Y; Department of Clinical Laboratory, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China., Cheung YC; Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Konggrid.35030.35, Kowloon, Hong Kong., Wai Chi Chan E; State Key Lab of Chemical Biology and Drug Discovery, Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hung Hom, Hong Kong., Chen S; Department of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Konggrid.35030.35, Kowloon, Hong Kong., Zhang R; Department of Clinical Laboratory, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. |
| Abstrakt: |
A novel Klebsiella pneumoniae carbapenemase (KPC) variant, KPC-93, was identified in two Klebsiella pneumoniae clinical isolates from a patient from China treated with ceftazidime-avibactam. KPC-93 possessed a five-amino-acids insertion (Pro-Asn-Asn-Arg-Ala) between Ambler positions 267 and 268 in KPC-2. Cloning and expression of the bla KPC-93 gene in Escherichia coli, followed by determination of minimum inhibitory concentration (MIC) values and kinetic parameters, showed that KPC-93 exhibited increased resistance to ceftazidime-avibactam, but a drastic decrease in carbapenemase activity. Our data highlight that a KPC variant conferring resistance to ceftazidime-avibactam could be easily induced by ceftazidime-avibactam treatment and that actions are required to control dissemination of these determinants. IMPORTANCE Ceftazidime-avibactam (CZA) is a novel β-lactam/β-lactamase inhibitor combination with activity against serine β-lactamases, including the Ambler class A enzyme KPC. However, during recent years, there have been increasing reports of emergence of new KPC variants that could confer resistance to CZA. This has limited its clinical application. Here, we reported a new KPC variant, KPC-93, that could confer CZA resistance. KPC-93 possessed a five-amino-acids insertion (Pro-Asn-Asn-Arg-Ala) between Ambler positions 267 and 268 in KPC-2. Our findings have revealed the potential risk of bla KPC gene mutations associated with CZA exposure over a short period of time. |
