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Diagn Microbiol Infect Dis. 2017 Jul;88(3):276-281. doi: 10.1016/j.diagmicrobio.2017.04.005. Epub 2017 Apr 12.

Mechanisms responsible for imipenem resistance among Pseudomonas aeruginosa clinical isolates exposed to imipenem concentrations within the mutant selection window.

Author information

1
Hygeia General Hospital, Athens, Greece.
2
Infectious Diseases Laboratory, 4th Department of Internal Medicine, University General Hospital "Attikon", Medical School, National and Kapodistrian University of Athens, Athens, Greece. Electronic address: egalani@med.uoa.gr.
3
Infectious Diseases Laboratory, 4th Department of Internal Medicine, University General Hospital "Attikon", Medical School, National and Kapodistrian University of Athens, Athens, Greece.
4
6th Department of Internal Medicine, Hygeia General Hospital, Athens, Greece.

Abstract

The aim of this study was to determine the propensities of imipenem to select for resistant Pseudomonas aeruginosa mutants by determining the mutant prevention concentrations (MPCs) for 9 unrelated clinical isolates and the accession of any relationship with mechanisms of resistance development. The MPC/MIC ratios ranged from 4 to 16. Detection of resistance mechanisms in the mutant derivatives of the nine isolates mainly revealed inactivating mutations in the gene coding for outer membrane protein OprD. Point mutations leading to premature stop codons or amino acid substitution S278P, ≥1bp deletion leading to frameshift mutations and interruption of the oprD by an insertion sequence, were observed. MPC and mutant selection window (MSW) are unique parameters that may guide the implementation of antimicrobial treatment, providing useful information about the necessary imipenem concentration needed in the infection area, in order to avoid the emergence of resistance, especially in clinical situations with high bacterial load.

KEYWORDS:

Imipenem-resistance; MPC; MSW; P. aeruginosa; oprD

[Indexed for MEDLINE]

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