Emergence of the New KPC-49 Variant Conferring an ESBL Phenotype with Resistance to Ceftazidime-Avibactam in the ST131-H30R1 <i>Escherichia coli</i> High-Risk Clone
We report the emergence of an isolate belonging to the sequence type (ST)131-<i>Escherichia coli</i> high-risk clone with ceftazidime-avibactam resistance recovered from a patient with bacteremia in 2019. Antimicrobial susceptibility was determined and whole genome sequencing (Illumina-N...
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MDPI AG
2021-01-01
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| Series: | Pathogens |
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| Online Access: | https://www.mdpi.com/2076-0817/10/1/67 |
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| author | Marta Hernández-García Javier Sánchez-López Laura Martínez-García Federico Becerra-Aparicio María Isabel Morosini Patricia Ruiz-Garbajosa Rafael Cantón |
| author_facet | Marta Hernández-García Javier Sánchez-López Laura Martínez-García Federico Becerra-Aparicio María Isabel Morosini Patricia Ruiz-Garbajosa Rafael Cantón |
| author_sort | Marta Hernández-García |
| collection | DOAJ |
| description | We report the emergence of an isolate belonging to the sequence type (ST)131-<i>Escherichia coli</i> high-risk clone with ceftazidime-avibactam resistance recovered from a patient with bacteremia in 2019. Antimicrobial susceptibility was determined and whole genome sequencing (Illumina-NovaSeq6000) and cloning experiments were performed to investigate its resistance phenotype. A KPC-3-producing <i>E. coli</i> isolate susceptible to ceftazidime-avibactam (MIC = 0.5/4 mg/L) and with non-wild type MIC of meropenem (8 mg/L) was detected in a blood culture performed at hospital admission. Following 10-days of standard ceftazidime-avibactam dose treatment, a second KPC-producing <i>E. coli</i> isolate with a phenotype resembling an extended-spectrum β-lactamase (ESBL) producer (meropenem 0.5 mg/L, piperacillin-tazobactam 16/8 mg/L) but resistant to ceftazidime-avibactam (16/4 mg/L) was recovered. Both <i>E. coli</i> isolates belonged to ST131, serotype O25:H4 and sublineage H30R1. Genomics analysis showed a <i>core</i> genome of 5,203,887 base pair with an evolutionary distance of 6 single nucleotide polymorphisms. A high content of resistance and virulence genes was detected in both isolates. The novel KPC-49 variant, an Arg-163-Ser mutant of <i>bla</i><sub>KPC-3</sub>, was detected in the isolate with resistance to ceftazidime-avibactam. Cloning experiments revealed that <i>bla</i><sub>KPC-49</sub> gene increases ceftazidime-avibactam MIC and decreases carbapenem MICs when using a porin deficient <i>Klebsiella pneumoniae</i> strain as a host. Both <i>bla</i><sub>KPC-3</sub> and <i>bla</i><sub>KPC-49</sub> genes were located on the transposon Tn<i>4401</i>a as a part of an IncF [F1:A2:B20] plasmid. The emergence of novel <i>bla</i><sub>KPC</sub> genes conferring decreased susceptibility to ceftazidime-avibactam and resembling ESBL production in the epidemic ST131-H30R1-<i>E. coli</i> high-risk clone presents a new challenge in clinical practice. |
| first_indexed | 2024-03-09T04:51:51Z |
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| institution | Directory Open Access Journal |
| issn | 2076-0817 |
| language | English |
| last_indexed | 2024-03-09T04:51:51Z |
| publishDate | 2021-01-01 |
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| spelling | doaj.art-4c23b5454a774395aa66040de5841be92023-12-03T13:09:33ZengMDPI AGPathogens2076-08172021-01-011016710.3390/pathogens10010067Emergence of the New KPC-49 Variant Conferring an ESBL Phenotype with Resistance to Ceftazidime-Avibactam in the ST131-H30R1 <i>Escherichia coli</i> High-Risk CloneMarta Hernández-García0Javier Sánchez-López1Laura Martínez-García2Federico Becerra-Aparicio3María Isabel Morosini4Patricia Ruiz-Garbajosa5Rafael Cantón6Servicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, SpainServicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, SpainServicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, SpainServicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, SpainServicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, SpainServicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, SpainServicio de Microbiología, Hospital Universitario Ramón y Cajal and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, SpainWe report the emergence of an isolate belonging to the sequence type (ST)131-<i>Escherichia coli</i> high-risk clone with ceftazidime-avibactam resistance recovered from a patient with bacteremia in 2019. Antimicrobial susceptibility was determined and whole genome sequencing (Illumina-NovaSeq6000) and cloning experiments were performed to investigate its resistance phenotype. A KPC-3-producing <i>E. coli</i> isolate susceptible to ceftazidime-avibactam (MIC = 0.5/4 mg/L) and with non-wild type MIC of meropenem (8 mg/L) was detected in a blood culture performed at hospital admission. Following 10-days of standard ceftazidime-avibactam dose treatment, a second KPC-producing <i>E. coli</i> isolate with a phenotype resembling an extended-spectrum β-lactamase (ESBL) producer (meropenem 0.5 mg/L, piperacillin-tazobactam 16/8 mg/L) but resistant to ceftazidime-avibactam (16/4 mg/L) was recovered. Both <i>E. coli</i> isolates belonged to ST131, serotype O25:H4 and sublineage H30R1. Genomics analysis showed a <i>core</i> genome of 5,203,887 base pair with an evolutionary distance of 6 single nucleotide polymorphisms. A high content of resistance and virulence genes was detected in both isolates. The novel KPC-49 variant, an Arg-163-Ser mutant of <i>bla</i><sub>KPC-3</sub>, was detected in the isolate with resistance to ceftazidime-avibactam. Cloning experiments revealed that <i>bla</i><sub>KPC-49</sub> gene increases ceftazidime-avibactam MIC and decreases carbapenem MICs when using a porin deficient <i>Klebsiella pneumoniae</i> strain as a host. Both <i>bla</i><sub>KPC-3</sub> and <i>bla</i><sub>KPC-49</sub> genes were located on the transposon Tn<i>4401</i>a as a part of an IncF [F1:A2:B20] plasmid. The emergence of novel <i>bla</i><sub>KPC</sub> genes conferring decreased susceptibility to ceftazidime-avibactam and resembling ESBL production in the epidemic ST131-H30R1-<i>E. coli</i> high-risk clone presents a new challenge in clinical practice.https://www.mdpi.com/2076-0817/10/1/67ST131-H30R1-<i>E. coli</i> high-risk cloneceftazidime-avibactam susceptibility<i>bla</i><sub>KPC-49</sub>whole genome sequencing |
| spellingShingle | Marta Hernández-García Javier Sánchez-López Laura Martínez-García Federico Becerra-Aparicio María Isabel Morosini Patricia Ruiz-Garbajosa Rafael Cantón Emergence of the New KPC-49 Variant Conferring an ESBL Phenotype with Resistance to Ceftazidime-Avibactam in the ST131-H30R1 <i>Escherichia coli</i> High-Risk Clone Pathogens ST131-H30R1-<i>E. coli</i> high-risk clone ceftazidime-avibactam susceptibility <i>bla</i><sub>KPC-49</sub> whole genome sequencing |
| title | Emergence of the New KPC-49 Variant Conferring an ESBL Phenotype with Resistance to Ceftazidime-Avibactam in the ST131-H30R1 <i>Escherichia coli</i> High-Risk Clone |
| title_full | Emergence of the New KPC-49 Variant Conferring an ESBL Phenotype with Resistance to Ceftazidime-Avibactam in the ST131-H30R1 <i>Escherichia coli</i> High-Risk Clone |
| title_fullStr | Emergence of the New KPC-49 Variant Conferring an ESBL Phenotype with Resistance to Ceftazidime-Avibactam in the ST131-H30R1 <i>Escherichia coli</i> High-Risk Clone |
| title_full_unstemmed | Emergence of the New KPC-49 Variant Conferring an ESBL Phenotype with Resistance to Ceftazidime-Avibactam in the ST131-H30R1 <i>Escherichia coli</i> High-Risk Clone |
| title_short | Emergence of the New KPC-49 Variant Conferring an ESBL Phenotype with Resistance to Ceftazidime-Avibactam in the ST131-H30R1 <i>Escherichia coli</i> High-Risk Clone |
| title_sort | emergence of the new kpc 49 variant conferring an esbl phenotype with resistance to ceftazidime avibactam in the st131 h30r1 i escherichia coli i high risk clone |
| topic | ST131-H30R1-<i>E. coli</i> high-risk clone ceftazidime-avibactam susceptibility <i>bla</i><sub>KPC-49</sub> whole genome sequencing |
| url | https://www.mdpi.com/2076-0817/10/1/67 |
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