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Association between clinical antibiotic resistance and susceptibility of Pseudomonas in the cystic fibrosis lung.


ABSTRACT:

Background and objectives

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 antibiotics. Here, we investigate correlations of sensitivity and resistance profiles of Pseudomonas aeruginosa that naturally adapted to antibiotics in the cystic fibrosis lung.

Methodology

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 13 MLST loci.

Result

Our study focused on 45 isolates from 13 patients under documented treatment with antibiotics. Forty percent of these 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 clones. However, genetically similar clones often had dissimilar resistance profiles. Isolates showed mutations in genes encoding cell wall synthesis, alginate production, efflux pumps and antibiotic modifying enzymes. Cross-resistance was commonly observed within antibiotic classes and between aminoglycosides and ?-lactam antibiotics. No evidence was found for consistent phenotypic resistance to one antibiotic and sensitivity to another within one genotype.

Conclusions and implications

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.

SUBMITTER: Jansen G 

PROVIDER: S-EPMC4906436 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Association between clinical antibiotic resistance and susceptibility of Pseudomonas in the cystic fibrosis lung.

Jansen Gunther G   Mahrt Niels N   Tueffers Leif L   Barbosa Camilo C   Harjes Malte M   Adolph Gernot G   Friedrichs Anette A   Krenz-Weinreich Annegret A   Rosenstiel Philip P   Schulenburg Hinrich H  

Evolution, medicine, and public health 20160614 1


<h4>Background and objectives</h4>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 antibiotics. Here, we investigate correlations of sensitivity and resistance profiles of Pseudomonas aeruginosa that naturally adapted to antibiotics in the cystic fibr  ...[more]

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