Development and Persistence of Antimicrobial Resistance in Pseudomonas aeruginosa : a Longitudinal Observation in Mechanically Ventilated Patients
| Autor: | Peter Rohner, Thilo Köhler, Paul Wood, Anita Reinhardt, Christian van Delden, Jean-Luc Claude Dumas, Bara Ricou |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Imipenem
Carbapenem Drug resistance medicine.disease_cause Polymerase Chain Reaction beta-Lactamases Microbiology Antibiotic resistance Bacterial Proteins Mechanisms of Resistance Drug Resistance Bacterial medicine Humans Pseudomonas Infections Pharmacology (medical) Longitudinal Studies Pathogen ddc:616 Pharmacology biology Pseudomonas aeruginosa Bacterial Proteins/genetics/ metabolism Anti-Bacterial Agents/ pharmacology/therapeutic use Pneumonia Ventilator-Associated Pneumonia Ventilator-Associated/ microbiology biology.organism_classification Antimicrobial Anti-Bacterial Agents Infectious Diseases Pseudomonas Infections/drug therapy Immunology Pseudomonas aeruginosa/ drug effects/genetics/isolation & purification Beta-Lactamases/biosynthesis/genetics Pseudomonadaceae medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy, Vol. 51, No 4 (2007) pp. 1341-1350 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.01278-06 |
| Popis: | 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 β-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 β-lactam and FQ was correlated with ampC and mexC gene expression levels, respectively, whereas imipenem resistance was attributable to decreased oprD expression. Combined β-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 β-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. |
| Databáze: | OpenAIRE |
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