1887

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Volume 71, Issue 11

Molecular patterns of clinically important fluoroquinolone resistance in multidrug-resistant isolates during nosocomial outbreaks in Shanghai, PR China No Access

Abstract

The soaring resistance of to fluoroquinolones in PR China has substantially limited the application of these antimicrobials, especially in those clinical settings that were threatened by persistent carbapenem-resistant (CRKP), necessitating strict implementation of antimicrobial stewardship and active enhanced surveillance of infection control.

There is interplay between plasmid-mediated quinolone resistance (PMQR) determinants and quinolone resistance-determining region (QRDR) mutations during the acquisition of a clinically important fluoroquinolone resistance (CI-FR) profile in multidrug-resistant (MDR-KP) isolates.

To investigate the high-risk CRKP clones responsible for nosocomial spread and analyse the molecular patterns of CI-FR in MDR-KP isolates in a tertiary hospital in Shanghai, PR China.

A total of 34 isolates, including 30 CRKPs, were molecularly characterized. Investigations included antimicrobial susceptibility tests, multilocus sequence typing (MLST) and genotyping, PCR sequencing and phylogenetic analysis for resistance-associated genes, and clinical information retrieval from medical records.

Two high-risk CRKP clones, ST11-64 and ST15-19/24, were identified as being responsible for nosocomial outbreaks in the intensive care unit (ICU) and the neurosurgery department, potentially by the respiratory route. QRDR mutations of both and were detected in isolates of ST15 (S83F/D87A/S80I), ST11 (S83I/D87G/S80I) and ST218 (D87A/S80I), respectively. The PMQR genes, S1, and AB, were present in 32 (94.1 %) of the isolates alone or in combination, co-occurring with genes () encoding β-lactamases, 16S rRNA methylases and putrescine ABC permeases. AcrR, an AcrAB transcriptional repressor, was insertion-inactivated by the IS5-like element in ST11 isolates. The encoding sequences of OmpK35 and OmpK36 genes were associated with specific STs and alleles. ST11, ST15-19 and ST218 isolates had frameshift disruptions in OmpK35 and specific GD insertions at position 134–135 in OmpK36. The 27 isolates with clinically important ciprofloxacin resistance (MICs ≥2 mg l) included 25 isolates (ST15, ST11, ST218) with multiple QRDR mutations, plus 1 with only 2 PMQR determinants (ST290-21) and another with an unknown resistance mechanism (ST65-72). Ciprofloxacin-susceptible isolates maintained intact genes, including two CRKPs each with ST13-74 (KPC-2 and NDM-1 coproducers) and ST65-72, plus carbapenem-susceptible isolates (ST15-24, ST65-72, ST107-173).

Under selective pressures, the accumulation of mutations of three types (QRDR, , 36) and the acquisition of resistance-conferring genes have continuously contributed to CI-FR in MDR-KP isolates.

  • Received:
  • Accepted:
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Keyword(s): carbapenem-resistant Klebsiella pneumoniae , fluoroquinolone resistance , MDR , PMQR , porin OmpK36 and QRDR
© 2022 The Authors
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2022-11-08
2024-04-20
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Molecular patterns of clinically important fluoroquinolone resistance in multidrug-resistant Klebsiella pneumoniae isolates during nosocomial outbreaks in Shanghai, PR China
J. Med. Microbiol. 71, 001583 (2022); https://doi.org/10.1099/jmm.0.001583
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