| Title | Association between clinical antibiotic resistance and susceptibility profiles of Pseudomonas aeruginosa in the cystic fibrosis lung |
| Study Type | Other |
| Abstract |
Cystic fibrosis patients suffer from chronic lung infections that require long-term antibiotic therapy. Pseudomonas readily evolve resistance, rendering antibiotics ineffective. In vitro experiments suggest that resistant bacteria may be treated by exploiting their collateral sensitivity to other an .. [more]tibiotics. Here, we investigate correlations of sensitivity and resistance profiles of Pseudomonas aeruginosa clones that naturally adapted to long-term antibiotic exposure in the cystic fibrosis lung. Resistance profiles for 13 antibiotics were obtained using broth dilution, E-test and VITEK mass spectroscopy. Genetic variants were determined from whole-genome sequences and interrelationships among isolates were analyzed using 14 MLST loci. Our study focused on 45 isolates from 13 patients under documented treatment with antibiotics. Fourty percent of these isolates were clinically resistant and 15% multi drug resistant. Colistin resistance was found once, despite continuous colistin treatment and even though colistin resistance can readily evolve experimentally in the laboratory. Patients typically harbored multiple genetically and phenotypically distinct P. aeruginosa clones. However, genetically similar clones often had dissimilar resistance profiles. Isolates showed mutations in genes encoding transcription factors, cell wall synthesis and alginate production, two-component sensors, multi drug efflux pumps and antibiotic modifying enzymes. Cross-resistance was commonly observed within antibiotic classes and between aminoglycosides and ß-lactam antibiotics. No evidence was found for consistent phenotypic resistance to one antibiotic and sensitivity to another. Evidence supporting potential collateral sensitivity in clinical P. aeruginosa isolates remains equivocal. However, cross-resistance within antibiotic classes is common. Colistin therapy is promising since resistance to it was rare despite its intensive use in the studied patients. [less]
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| Description |
Cystic fibrosis patients suffer from chronic lung infections that require long-term antibiotic therapy. Pseudomonas readily evolve resistance, rendering antibiotics ineffective. In vitro experiments suggest that resistant bacteria may be treated by exploiting their collateral sensitivity to other an .. [more]tibiotics. Here, we investigate correlations of sensitivity and resistance profiles of Pseudomonas aeruginosa clones that naturally adapted to long-term antibiotic exposure in the cystic fibrosis lung. Resistance profiles for 13 antibiotics were obtained using broth dilution, E-test and VITEK mass spectroscopy. Genetic variants were determined from whole-genome sequences and interrelationships among isolates were analyzed using 14 MLST loci. Our study focused on 45 isolates from 13 patients under documented treatment with antibiotics. Fourty percent of these isolates were clinically resistant and 15% multi drug resistant. Colistin resistance was found once, despite continuous colistin treatment and even though colistin resistance can readily evolve experimentally in the laboratory. Patients typically harbored multiple genetically and phenotypically distinct P. aeruginosa clones. However, genetically similar clones often had dissimilar resistance profiles. Isolates showed mutations in genes encoding transcription factors, cell wall synthesis and alginate production, two-component sensors, multi drug efflux pumps and antibiotic modifying enzymes. Cross-resistance was commonly observed within antibiotic classes and between aminoglycosides and ß-lactam antibiotics. No evidence was found for consistent phenotypic resistance to one antibiotic and sensitivity to another. Evidence supporting potential collateral sensitivity in clinical P. aeruginosa isolates remains equivocal. However, cross-resistance within antibiotic classes is common. Colistin therapy is promising since resistance to it was rare despite its intensive use in the studied patients. [less]
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| Center Name | ZOOLOGICAL INSTITUTE KIEL |
