1887

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Volume 66, Issue 11

Risk factors for and role of OprD protein in increasing minimal inhibitory concentrations of carbapenems in clinical isolates of Free

Abstract

This study examined the risk factors for, and molecular mechanisms underlying, the increase in carbapenem minimum inhibitory concentrations (MICs) in clinical isolates of .

Consecutive clinical isolates of were collected. The MicroScan WalkAway system detected more than fourfold increases in the MICs of carbapenems in isolates serially recovered from some patients during their clinical course. The clinical risk factors associated with this increase were examined by multiple logistic regression analysis. Western blot analysis and nucleotide sequencing of the gene of 19 clonally related and paired isolates from the same patients were undertaken to examine the mechanisms underlying the increase in MICs.

The results showed that prior use of carbapenems (OR, 2.799; 95 % CI, 1.088–7.200; =0.033) and the use of ventilators or tracheostomies (OR, 2.648; 95 % CI, 1.051–6.671; =0.039) were risk factors for increased carbapenem MICs. Analysis of the underlying mechanisms revealed that loss of functional OprD protein due to mutation of the gene tended to occur in isolates with imipenem MICs of more than 8 µg ml; a reduction in OprD expression was observed in isolates with imipenem MICs of 4 or 8 µg ml. This difference in the resistance mechanism was not correlated with the MICs of meropenem.

This difference in the resistance mechanism of indicates a critical breakpoint at an imipenem MIC of 8 µg ml, in accordance with EUCAST criteria. Reducing carbapenem use will prevent clinical isolates from developing resistance to carbapenems.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): carbapenems , MICs , OprD and P. aeruginosa
© 2017 The Authors
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2017-11-01
2024-04-24
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Risk factors for and role of OprD protein in increasing minimal inhibitory concentrations of carbapenems in clinical isolates of Pseudomonas aeruginosa
J. Med. Microbiol. 66, 1562 (2017); https://doi.org/10.1099/jmm.0.000601
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