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Genomic characterization of a KPC-23-producing Klebsiella pneumoniae ST258 clinical isolate resistant to ceftazidime-avibactam
- Source :
- Clinical Microbiology and Infection. 25:763.e5-763.e8
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
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.
- Subjects :
- 0301 basic medicine
Microbiology (medical)
Carbapenem
Imipenem
Klebsiella pneumoniae
Avibactam
030106 microbiology
Ceftazidime
Microbial Sensitivity Tests
Biology
Meropenem
beta-Lactamases
Microbiology
03 medical and health sciences
chemistry.chemical_compound
Minimum inhibitory concentration
0302 clinical medicine
Drug Resistance, Bacterial
medicine
Humans
030212 general & internal medicine
Greece
Whole Genome Sequencing
Genomics
General Medicine
biochemical phenomena, metabolism, and nutrition
Ceftazidime/avibactam
biology.organism_classification
Anti-Bacterial Agents
Klebsiella Infections
Drug Combinations
Infectious Diseases
chemistry
beta-Lactamase Inhibitors
Azabicyclo Compounds
Genome, Bacterial
medicine.drug
Subjects
Details
- ISSN :
- 1198743X
- Volume :
- 25
- Database :
- OpenAIRE
- Journal :
- Clinical Microbiology and Infection
- Accession number :
- edsair.doi.dedup.....8a65ddd1bffc3eec7beb92fbcb1d9e1e