Identification of a KPC Variant Conferring Resistance to Ceftazidime-Avibactam from ST11 Carbapenem-Resistant Klebsiella pneumoniae Strains
ABSTRACT 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...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2022-04-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.02655-21 |
| _version_ | 1811303486860558336 |
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| author | Yuchen Wu Xuemei Yang Congcong Liu Yanyan Zhang Yan Chu Cheung Edward Wai Chi Chan Sheng Chen Rong Zhang |
| author_facet | Yuchen Wu Xuemei Yang Congcong Liu Yanyan Zhang Yan Chu Cheung Edward Wai Chi Chan Sheng Chen Rong Zhang |
| author_sort | Yuchen Wu |
| collection | DOAJ |
| description | ABSTRACT 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 blaKPC-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 blaKPC gene mutations associated with CZA exposure over a short period of time. |
| first_indexed | 2024-04-13T07:47:48Z |
| format | Article |
| id | doaj.art-3e469f76c5e14800ac03ad44322c134a |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-04-13T07:47:48Z |
| publishDate | 2022-04-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-3e469f76c5e14800ac03ad44322c134a2022-12-22T02:55:37ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972022-04-0110210.1128/spectrum.02655-21Identification of a KPC Variant Conferring Resistance to Ceftazidime-Avibactam from ST11 Carbapenem-Resistant Klebsiella pneumoniae StrainsYuchen Wu0Xuemei Yang1Congcong Liu2Yanyan Zhang3Yan Chu Cheung4Edward Wai Chi Chan5Sheng Chen6Rong Zhang7Department of Clinical Laboratory, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong KongDepartment of Clinical Laboratory, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Clinical Laboratory, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong KongState Key Lab of Chemical Biology and Drug Discovery, Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hung Hom, Hong KongDepartment of Infectious Diseases and Public Health, Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong KongDepartment of Clinical Laboratory, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaABSTRACT 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 blaKPC-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 blaKPC gene mutations associated with CZA exposure over a short period of time.https://journals.asm.org/doi/10.1128/spectrum.02655-21KPCceftazidime-avibactamKlebsiella pneumoniae |
| spellingShingle | Yuchen Wu Xuemei Yang Congcong Liu Yanyan Zhang Yan Chu Cheung Edward Wai Chi Chan Sheng Chen Rong Zhang Identification of a KPC Variant Conferring Resistance to Ceftazidime-Avibactam from ST11 Carbapenem-Resistant Klebsiella pneumoniae Strains Microbiology Spectrum KPC ceftazidime-avibactam Klebsiella pneumoniae |
| title | Identification of a KPC Variant Conferring Resistance to Ceftazidime-Avibactam from ST11 Carbapenem-Resistant Klebsiella pneumoniae Strains |
| title_full | Identification of a KPC Variant Conferring Resistance to Ceftazidime-Avibactam from ST11 Carbapenem-Resistant Klebsiella pneumoniae Strains |
| title_fullStr | Identification of a KPC Variant Conferring Resistance to Ceftazidime-Avibactam from ST11 Carbapenem-Resistant Klebsiella pneumoniae Strains |
| title_full_unstemmed | Identification of a KPC Variant Conferring Resistance to Ceftazidime-Avibactam from ST11 Carbapenem-Resistant Klebsiella pneumoniae Strains |
| title_short | Identification of a KPC Variant Conferring Resistance to Ceftazidime-Avibactam from ST11 Carbapenem-Resistant Klebsiella pneumoniae Strains |
| title_sort | identification of a kpc variant conferring resistance to ceftazidime avibactam from st11 carbapenem resistant klebsiella pneumoniae strains |
| topic | KPC ceftazidime-avibactam Klebsiella pneumoniae |
| url | https://journals.asm.org/doi/10.1128/spectrum.02655-21 |
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