Nosocomial spread of ceftazidime-resistant Klebsiella pneumoniae strains producing a novel class A β-lactamase, GES-3, in a neonatal intensive care unit in Japan

Jun Ichi Wachino, Yohei Doi, Kunikazu Yamane, Naohiro Shibata, Tetsuya Yagi, Takako Kubota, Hideo Ito, Yoshichika Arakawa

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Klebsiella pneumoniae strain KG525, which showed high-level resistance to broad-spectrum cephalosporins, was isolated from the neonatal intensive care unit (NICU) of a Japanese hospital in March 2002. The ceftazidime resistance of strain KG525 was transferable to Escherichia coli CSH-2 by conjugation. Cloning and sequence analysis revealed that production of a novel extended-spectrum class A β-lactamase (pI 7.0), designated GES-3, which had two amino acid substitutions of M62T and E104K on the basis of the sequence of GES-1, was responsible for resistance in strain KG525 and its transconjugant. The bla GES-3 gene was located as the first gene cassette in a class 1 integron that also contained an aacA1-orfG fused gene cassette and one unique cassette that has not been described in other class 1 integrons and ended with a truncated 3′ conserved segment by insertion of IS26. Another five ceftazidime-resistant K. pneumoniae strains, strains KG914, KG1116, KG545, KG502, and KG827, which were isolated from different neonates during a 1-year period in the same NICU where strain KG525 had been isolated, were also positive for GES-type β-lactamase genes by PCR. Pulsed-field gel electrophoresis and enterobacterial repetitive intergenic consensus-PCR analyses displayed genetic relatedness among the six K. pneumoniae strains. Southern hybridization analysis with a GES-type β-lactamase gene-specific probe showed that the locations of blaGES were multiple and diverse among the six strains. These findings suggest that within the NICU setting genetically related K. pneumoniae strains carrying the blaGES gene were ambushed with genetic rearrangements that caused the multiplication and translocation of the blaGES gene.

Original languageEnglish
Pages (from-to)1960-1967
Number of pages8
JournalAntimicrobial agents and chemotherapy
Volume48
Issue number6
DOIs
Publication statusPublished - 01-06-2004

Fingerprint

Ceftazidime
Neonatal Intensive Care Units
Klebsiella pneumoniae
Japan
Genes
Integrons
Polymerase Chain Reaction
Pulsed Field Gel Electrophoresis
Amino Acid Substitution
Cephalosporins
Sequence Analysis
Organism Cloning
Escherichia coli

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Wachino, Jun Ichi ; Doi, Yohei ; Yamane, Kunikazu ; Shibata, Naohiro ; Yagi, Tetsuya ; Kubota, Takako ; Ito, Hideo ; Arakawa, Yoshichika. / Nosocomial spread of ceftazidime-resistant Klebsiella pneumoniae strains producing a novel class A β-lactamase, GES-3, in a neonatal intensive care unit in Japan. In: Antimicrobial agents and chemotherapy. 2004 ; Vol. 48, No. 6. pp. 1960-1967.
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abstract = "Klebsiella pneumoniae strain KG525, which showed high-level resistance to broad-spectrum cephalosporins, was isolated from the neonatal intensive care unit (NICU) of a Japanese hospital in March 2002. The ceftazidime resistance of strain KG525 was transferable to Escherichia coli CSH-2 by conjugation. Cloning and sequence analysis revealed that production of a novel extended-spectrum class A β-lactamase (pI 7.0), designated GES-3, which had two amino acid substitutions of M62T and E104K on the basis of the sequence of GES-1, was responsible for resistance in strain KG525 and its transconjugant. The bla GES-3 gene was located as the first gene cassette in a class 1 integron that also contained an aacA1-orfG fused gene cassette and one unique cassette that has not been described in other class 1 integrons and ended with a truncated 3′ conserved segment by insertion of IS26. Another five ceftazidime-resistant K. pneumoniae strains, strains KG914, KG1116, KG545, KG502, and KG827, which were isolated from different neonates during a 1-year period in the same NICU where strain KG525 had been isolated, were also positive for GES-type β-lactamase genes by PCR. Pulsed-field gel electrophoresis and enterobacterial repetitive intergenic consensus-PCR analyses displayed genetic relatedness among the six K. pneumoniae strains. Southern hybridization analysis with a GES-type β-lactamase gene-specific probe showed that the locations of blaGES were multiple and diverse among the six strains. These findings suggest that within the NICU setting genetically related K. pneumoniae strains carrying the blaGES gene were ambushed with genetic rearrangements that caused the multiplication and translocation of the blaGES gene.",
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Nosocomial spread of ceftazidime-resistant Klebsiella pneumoniae strains producing a novel class A β-lactamase, GES-3, in a neonatal intensive care unit in Japan. / Wachino, Jun Ichi; Doi, Yohei; Yamane, Kunikazu; Shibata, Naohiro; Yagi, Tetsuya; Kubota, Takako; Ito, Hideo; Arakawa, Yoshichika.

In: Antimicrobial agents and chemotherapy, Vol. 48, No. 6, 01.06.2004, p. 1960-1967.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Nosocomial spread of ceftazidime-resistant Klebsiella pneumoniae strains producing a novel class A β-lactamase, GES-3, in a neonatal intensive care unit in Japan

AU - Wachino, Jun Ichi

AU - Doi, Yohei

AU - Yamane, Kunikazu

AU - Shibata, Naohiro

AU - Yagi, Tetsuya

AU - Kubota, Takako

AU - Ito, Hideo

AU - Arakawa, Yoshichika

PY - 2004/6/1

Y1 - 2004/6/1

N2 - Klebsiella pneumoniae strain KG525, which showed high-level resistance to broad-spectrum cephalosporins, was isolated from the neonatal intensive care unit (NICU) of a Japanese hospital in March 2002. The ceftazidime resistance of strain KG525 was transferable to Escherichia coli CSH-2 by conjugation. Cloning and sequence analysis revealed that production of a novel extended-spectrum class A β-lactamase (pI 7.0), designated GES-3, which had two amino acid substitutions of M62T and E104K on the basis of the sequence of GES-1, was responsible for resistance in strain KG525 and its transconjugant. The bla GES-3 gene was located as the first gene cassette in a class 1 integron that also contained an aacA1-orfG fused gene cassette and one unique cassette that has not been described in other class 1 integrons and ended with a truncated 3′ conserved segment by insertion of IS26. Another five ceftazidime-resistant K. pneumoniae strains, strains KG914, KG1116, KG545, KG502, and KG827, which were isolated from different neonates during a 1-year period in the same NICU where strain KG525 had been isolated, were also positive for GES-type β-lactamase genes by PCR. Pulsed-field gel electrophoresis and enterobacterial repetitive intergenic consensus-PCR analyses displayed genetic relatedness among the six K. pneumoniae strains. Southern hybridization analysis with a GES-type β-lactamase gene-specific probe showed that the locations of blaGES were multiple and diverse among the six strains. These findings suggest that within the NICU setting genetically related K. pneumoniae strains carrying the blaGES gene were ambushed with genetic rearrangements that caused the multiplication and translocation of the blaGES gene.

AB - Klebsiella pneumoniae strain KG525, which showed high-level resistance to broad-spectrum cephalosporins, was isolated from the neonatal intensive care unit (NICU) of a Japanese hospital in March 2002. The ceftazidime resistance of strain KG525 was transferable to Escherichia coli CSH-2 by conjugation. Cloning and sequence analysis revealed that production of a novel extended-spectrum class A β-lactamase (pI 7.0), designated GES-3, which had two amino acid substitutions of M62T and E104K on the basis of the sequence of GES-1, was responsible for resistance in strain KG525 and its transconjugant. The bla GES-3 gene was located as the first gene cassette in a class 1 integron that also contained an aacA1-orfG fused gene cassette and one unique cassette that has not been described in other class 1 integrons and ended with a truncated 3′ conserved segment by insertion of IS26. Another five ceftazidime-resistant K. pneumoniae strains, strains KG914, KG1116, KG545, KG502, and KG827, which were isolated from different neonates during a 1-year period in the same NICU where strain KG525 had been isolated, were also positive for GES-type β-lactamase genes by PCR. Pulsed-field gel electrophoresis and enterobacterial repetitive intergenic consensus-PCR analyses displayed genetic relatedness among the six K. pneumoniae strains. Southern hybridization analysis with a GES-type β-lactamase gene-specific probe showed that the locations of blaGES were multiple and diverse among the six strains. These findings suggest that within the NICU setting genetically related K. pneumoniae strains carrying the blaGES gene were ambushed with genetic rearrangements that caused the multiplication and translocation of the blaGES gene.

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