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Antimicrob. Agents Chemother. doi:10.1128/AAC.01278-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Development and persistence of antimicrobial resistance in Pseudomonas aeruginosa: a longitudinal observation in mechanically ventilated patients

Département de Microbiologie et de Médecine Moléculaire, Centre Médical Universitaire de Genève; Laboratoire Central de Bactériologie; Service des Soins Intensifs, Service des Maladies Infectieuses, Hôpital Universitaire de Genève, Suisse

^* To whom correspondence should be addressed. Email: Christian.vandelden{at}medecine.unige.ch.

	Abstract

Intubated patients become frequently colonized by Pseudomonas aeruginosa, subsequently responsible for ventilator-associated pneumonia. This pathogen readily acquires antimicrobial 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 period during which they had received carbapenem, fluoroquinolone (FQ) or combined -lactam-aminoglycoside therapies. We tested antimicrobial resistance phenotypes by susceptibility testing and used quantitative RealTime-PCR to measure expression of resistance determinants. Within 10 days after initiation of therapy, all treatment regimens selected resistant isolates. Resistance to -lactam and FQ was correlated with ampC and mexC gene expression levels, respectively, whereas imipenem resistance was attributable to decreased oprD expression. Combined -lactam-aminoglycoside resistance was associated with appearance of small colony variants. Imipenem and FQ resistance persisted for prolonged time once the selecting antimicrobial treatment had been discontinued. In contrast resistance to -lactams rapidly disappeared after removal of the selective pressure, to reappear promptly upon renewed exposure.

Our results suggest that resistant P. aeruginosa are selected in less than 10 days independently of the antimicrobial class. Different resistance mechanisms lead to loss or persistence of resistance after removal of the selecting agent. Even if resistant isolates are not evident on culture, these may persist in the lung and can rapidly be reselected.

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