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

Article Article scientifique Article Development and persistence of antimicrobial resistance in Pseudomonas aeruginosa: a longitudinal observation in mechanically ventilated patients eng 2007 author Reinhardt Anita 585156 author Kohler Thilo 0000-0003-4889-9492 23327 author Wood Paul 548203 author Rohner Peter 129742 author Dumas Jean-Luc Claude 135741 author Ricou Bara 127716 author Van Delden Christian 24088 1341-1350 10.1128/AAC.01278-06 17261619 0066-4804 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1855521/pdf/1278-06.pdf 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. Anti-Bacterial Agents/ pharmacology/therapeutic use Bacterial Proteins/genetics/ metabolism Drug Resistance, Bacterial Humans Longitudinal Studies Pneumonia, Ventilator-Associated/ microbiology Polymerase Chain Reaction Pseudomonas Infections/drug therapy Pseudomonas aeruginosa/ drug effects/genetics/isolation & purification Beta-Lactamases/biosynthesis/genetics Dewey 616 56 Département de médecine 221 false Antimicrobial agents and chemotherapy 51 4 b3f95a51-f9a2-4fc1-b588-b6db1f8eb135 Article Restricted file1.pdf 569494 application/pdf restrictedAccess Faculté de médecine / Section de médecine clinique / Département de médecine

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Development and persistence of antimicrobial resistance in Pseudomonas aeruginosa: a longitudinal observation in mechanically ventilated patients	Antimicrobial agents and chemotherapy			2007	589	0

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Reinhardt, Anita