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Development and persistence of antimicrobial resistance in Pseudomonas aeruginosa: a longitudinal observation in mechanically ventilated patients.
- Source :
-
Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2007 Apr; Vol. 51 (4), pp. 1341-50. Date of Electronic Publication: 2007 Jan 29. - Publication Year :
- 2007
-
Abstract
- Intubated patients frequently become colonized by Pseudomonas aeruginosa, which is subsequently responsible for ventilator-associated pneumonia. This pathogen readily acquires resistance against available antimicrobials. Depending on the resistance mechanism selected for, resistance might either be lost or persist after removal of the selective pressure. We investigated the rapidity of selection, as well as the persistence, of antimicrobial resistance and determined the underlying mechanisms. We selected 109 prospectively collected P. aeruginosa tracheal isolates from two patients based on their prolonged intubation and colonization periods, during which they had received carbapenem, fluoroquinolone (FQ), or combined beta-lactam-aminoglycoside therapies. We determined antimicrobial resistance phenotypes by susceptibility testing and used quantitative real-time PCR to measure the expression of resistance determinants. Within 10 days after the initiation of therapy, all treatment regimens selected resistant isolates. Resistance to beta-lactam and FQ was correlated with ampC and mexC gene expression levels, respectively, whereas imipenem resistance was attributable to decreased oprD expression. Combined beta-lactam-aminoglycoside resistance was associated with the appearance of small-colony variants. Imipenem and FQ resistance persisted for prolonged times once the selecting antimicrobial treatment had been discontinued. In contrast, resistance to beta-lactams disappeared rapidly after removal of the selective pressure, to reappear promptly upon renewed exposure. Our results suggest that resistant P. aeruginosa is selected in less than 10 days independently of the antimicrobial class. Different resistance mechanisms lead to the loss or persistence of resistance after the removal of the selecting agent. Even if resistant isolates are not evident upon culture, they may persist in the lung and can be rapidly reselected.
- Subjects :
- Anti-Bacterial Agents therapeutic use
Bacterial Proteins genetics
Humans
Longitudinal Studies
Polymerase Chain Reaction
Pseudomonas Infections drug therapy
Pseudomonas aeruginosa genetics
Pseudomonas aeruginosa isolation & purification
beta-Lactamases biosynthesis
beta-Lactamases genetics
Anti-Bacterial Agents pharmacology
Bacterial Proteins metabolism
Drug Resistance, Bacterial
Pneumonia, Ventilator-Associated microbiology
Pseudomonas aeruginosa drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0066-4804
- Volume :
- 51
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Antimicrobial agents and chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 17261619
- Full Text :
- https://doi.org/10.1128/AAC.01278-06