Emergence of the New KPC-49 Variant Conferring an ESBL Phenotype with Resistance to Ceftazidime-Avibactam in the ST131-H30R1 Escherichia coli High-Risk Clone
We report the emergence of an isolate belonging to the sequence type (ST)131-Escherichia coli 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 E. coli 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 E. coli 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 E. coli isolates belonged to ST131, serotype O25:H4 and sublineage H30R1. Genomics analysis showed a core 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 blaKPC-3, was detected in the isolate with resistance to ceftazidime-avibactam. Cloning experiments revealed that blaKPC-49 gene increases ceftazidime-avibactam MIC and decreases carbapenem MICs when using a porin deficient Klebsiella pneumoniae strain as a host. Both blaKPC-3 and blaKPC-49 genes were located on the transposon Tn4401a as a part of an IncF [F1:A2:B20] plasmid. The emergence of novel blaKPC genes conferring decreased susceptibility to ceftazidime-avibactam and resembling ESBL production in the epidemic ST131-H30R1-E. coli high-risk clone presents a new challenge in clinical practice.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
|---|---|
| Enthalten in: |
Pathogens (Basel, Switzerland) - 10(2021), 1 vom: 14. Jan. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Hernández-García, Marta [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
BlaKPC-49 |
|---|
| Anmerkungen: |
Date Revised 18.02.2021 published: Electronic Citation Status PubMed-not-MEDLINE |
|---|
| doi: |
10.3390/pathogens10010067 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM320290018 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM320290018 | ||
| 003 | DE-627 | ||
| 005 | 20231225173247.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/pathogens10010067 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1067.xml |
| 035 | |a (DE-627)NLM320290018 | ||
| 035 | |a (NLM)33466574 | ||
| 035 | |a (PII)67 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Hernández-García, Marta |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Emergence of the New KPC-49 Variant Conferring an ESBL Phenotype with Resistance to Ceftazidime-Avibactam in the ST131-H30R1 Escherichia coli High-Risk Clone |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 18.02.2021 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a We report the emergence of an isolate belonging to the sequence type (ST)131-Escherichia coli 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 E. coli 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 E. coli 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 E. coli isolates belonged to ST131, serotype O25:H4 and sublineage H30R1. Genomics analysis showed a core 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 blaKPC-3, was detected in the isolate with resistance to ceftazidime-avibactam. Cloning experiments revealed that blaKPC-49 gene increases ceftazidime-avibactam MIC and decreases carbapenem MICs when using a porin deficient Klebsiella pneumoniae strain as a host. Both blaKPC-3 and blaKPC-49 genes were located on the transposon Tn4401a as a part of an IncF [F1:A2:B20] plasmid. The emergence of novel blaKPC genes conferring decreased susceptibility to ceftazidime-avibactam and resembling ESBL production in the epidemic ST131-H30R1-E. coli high-risk clone presents a new challenge in clinical practice | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a ST131-H30R1-E. coli high-risk clone | |
| 650 | 4 | |a blaKPC-49 | |
| 650 | 4 | |a ceftazidime-avibactam susceptibility | |
| 650 | 4 | |a whole genome sequencing | |
| 700 | 1 | |a Sánchez-López, Javier |e verfasserin |4 aut | |
| 700 | 1 | |a Martínez-García, Laura |e verfasserin |4 aut | |
| 700 | 1 | |a Becerra-Aparicio, Federico |e verfasserin |4 aut | |
| 700 | 1 | |a Morosini, María Isabel |e verfasserin |4 aut | |
| 700 | 1 | |a Ruiz-Garbajosa, Patricia |e verfasserin |4 aut | |
| 700 | 1 | |a Cantón, Rafael |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Pathogens (Basel, Switzerland) |d 2011 |g 10(2021), 1 vom: 14. Jan. |w (DE-627)NLM22512761X |x 2076-0817 |7 nnns |
| 773 | 1 | 8 | |g volume:10 |g year:2021 |g number:1 |g day:14 |g month:01 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3390/pathogens10010067 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 10 |j 2021 |e 1 |b 14 |c 01 | ||