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Genomic characterization of a KPC-23-producing Klebsiella pneumoniae ST258 clinical isolate resistant to ceftazidime-avibactam.
Clin Microbiol Infect 2019; 25(6):763.e5-763.e8CM

Abstract

OBJECTIVES

We characterized the first ceftazidime-avibactam-resistant KPC-producing-Klebsiella pneumoniae clinical isolate detected in Greece, before the introduction of ceftazidime-avibactam in clinical practice.

METHODS

K. pneumoniae KP-90 was isolated from a hospitalized patient in Thessaloniki during a nationwide surveillance study conducted between 2014 and 2016. Antimicrobial susceptibility was tested against a panel of agents. Whole-genome sequencing (Ion Torrent TM platform) of the isolate was carried out to identify the acquired resistance genes and mutations that were associated with ceftazidime-avibactam resistance.

RESULTS

The K. pneumoniae isolate belonged to multilocus sequence type ST258 and harboured blaKPC-23 as the only carbapenemase gene. The isolate had a minimum inhibitory concentration (MIC) of 16 mg/L to ceftazidime-avibactam and was highly resistant to imipenem, meropenem (MICs, 512 mg/L) and ceftazidime (MIC, >1024 mg/L). blaKPC-23 was detected on a Tn4401a transposon, located on a pKPQIL-type plasmid. A non-functional outer membrane protein OmpK35 and an OmpK36 variant that had been previously associated with K. pneumoniae isolates of ST258 were detected. Transformation studies with Escherichia coli TOP10 showed that KPC-23 offered similar carbapenem MICs as KPC-2 and KPC-3. However, KPC-23 conferred a four-fold higher ceftazidime MIC (>1024 mg/L), which in the presence of avibactam was reduced (>7-fold) to 8 mg/L, which is just within the limit of the susceptibility breakpoint.

CONCLUSIONS

Ceftazidime-avibactam resistance in a KPC-23- producing K. pneumoniae clinical isolate was due to increased ceftazidime hydrolysis and was likely enhanced by OmpK35 porin deficiency.

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    • Authors+Show Affiliations

    Galani I
    Fourth Department of Internal Medicine, Infectious Diseases Laboratory, Molecular Biology Section, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece. Electronic address: egalani@med.uoa.gr.
    Antoniadou A
    Fourth Department of Internal Medicine, Infectious Diseases Laboratory, Molecular Biology Section, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.
    Karaiskos I
    First Internal Medicine & Infectious Diseases Clinic, Hygeia General Hospital, Athens, Greece.
    Kontopoulou K
    Department of Microbiology, General Hospital of Thessaloniki 'G. Gennimatas', Thessaloniki, Greece.
    Giamarellou H
    First Internal Medicine & Infectious Diseases Clinic, Hygeia General Hospital, Athens, Greece.
    Souli M
    Fourth Department of Internal Medicine, Infectious Diseases Laboratory, Molecular Biology Section, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.

    MeSH

    Anti-Bacterial AgentsAzabicyclo CompoundsCeftazidimeDrug CombinationsDrug Resistance, BacterialGenome, BacterialGenomicsGreeceHumansKlebsiella InfectionsKlebsiella pneumoniaeMicrobial Sensitivity TestsWhole Genome Sequencingbeta-Lactamase Inhibitorsbeta-Lactamases

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    30928562

    Citation

    Galani, I, et al. "Genomic Characterization of a KPC-23-producing Klebsiella Pneumoniae ST258 Clinical Isolate Resistant to Ceftazidime-avibactam." Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases, vol. 25, no. 6, 2019, pp. 763.e5-763.e8.
    Galani I, Antoniadou A, Karaiskos I, et al. Genomic characterization of a KPC-23-producing Klebsiella pneumoniae ST258 clinical isolate resistant to ceftazidime-avibactam. Clin Microbiol Infect. 2019;25(6):763.e5-763.e8.
    Galani, I., Antoniadou, A., Karaiskos, I., Kontopoulou, K., Giamarellou, H., & Souli, M. (2019). Genomic characterization of a KPC-23-producing Klebsiella pneumoniae ST258 clinical isolate resistant to ceftazidime-avibactam. Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases, 25(6), pp. 763.e5-763.e8. doi:10.1016/j.cmi.2019.03.011.
    Galani I, et al. Genomic Characterization of a KPC-23-producing Klebsiella Pneumoniae ST258 Clinical Isolate Resistant to Ceftazidime-avibactam. Clin Microbiol Infect. 2019;25(6):763.e5-763.e8. PubMed PMID: 30928562.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Genomic characterization of a KPC-23-producing Klebsiella pneumoniae ST258 clinical isolate resistant to ceftazidime-avibactam. AU - Galani,I, AU - Antoniadou,A, AU - Karaiskos,I, AU - Kontopoulou,K, AU - Giamarellou,H, AU - Souli,M, Y1 - 2019/03/28/ PY - 2018/12/07/received PY - 2019/02/15/revised PY - 2019/03/09/accepted PY - 2019/4/1/pubmed PY - 2019/4/1/medline PY - 2019/4/1/entrez KW - Carbapenem-resistant Enterobacteriaceae KW - Carbapenemase KW - KPC mutations KW - Meropenem-vaborbactam KW - Porin deficiency SP - 763.e5 EP - 763.e8 JF - Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases JO - Clin. Microbiol. Infect. VL - 25 IS - 6 N2 - OBJECTIVES: We characterized the first ceftazidime-avibactam-resistant KPC-producing-Klebsiella pneumoniae clinical isolate detected in Greece, before the introduction of ceftazidime-avibactam in clinical practice. METHODS: K. pneumoniae KP-90 was isolated from a hospitalized patient in Thessaloniki during a nationwide surveillance study conducted between 2014 and 2016. Antimicrobial susceptibility was tested against a panel of agents. Whole-genome sequencing (Ion Torrent TM platform) of the isolate was carried out to identify the acquired resistance genes and mutations that were associated with ceftazidime-avibactam resistance. RESULTS: The K. pneumoniae isolate belonged to multilocus sequence type ST258 and harboured blaKPC-23 as the only carbapenemase gene. The isolate had a minimum inhibitory concentration (MIC) of 16 mg/L to ceftazidime-avibactam and was highly resistant to imipenem, meropenem (MICs, 512 mg/L) and ceftazidime (MIC, >1024 mg/L). blaKPC-23 was detected on a Tn4401a transposon, located on a pKPQIL-type plasmid. A non-functional outer membrane protein OmpK35 and an OmpK36 variant that had been previously associated with K. pneumoniae isolates of ST258 were detected. Transformation studies with Escherichia coli TOP10 showed that KPC-23 offered similar carbapenem MICs as KPC-2 and KPC-3. However, KPC-23 conferred a four-fold higher ceftazidime MIC (>1024 mg/L), which in the presence of avibactam was reduced (>7-fold) to 8 mg/L, which is just within the limit of the susceptibility breakpoint. CONCLUSIONS: Ceftazidime-avibactam resistance in a KPC-23- producing K. pneumoniae clinical isolate was due to increased ceftazidime hydrolysis and was likely enhanced by OmpK35 porin deficiency. SN - 1469-0691 UR - https://www.unboundmedicine.com/medline/citation/30928562/Genomic_characterization_of_a_KPC_23_producing_Klebsiella_pneumoniae_ST258_clinical_isolate_resistant_to_ceftazidime_avibactam_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1198-743X(19)30113-2 DB - PRIME DP - Unbound Medicine ER -

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