Temporal changes in resistance mechanisms in colonizing Escherichia coli isolates with reduced susceptibility to fluoroquinolones

Abstract

The objective of this study was to characterize the temporal variability of fluoroquinolone resistance mechanisms among Escherichia coli colonizing the gastrointestinal tract of hospitalized patients. Patients with new fluoroquinolone-resistant E. coli (FQREC) colonization were followed with serial fecal sampling until discharge or death. Genetic mechanism(s) of resistance for all FQREC isolates were characterized, including mutations in gyrA and parC and efflux pump overexpression. Of 451 subjects, 73 (16.2%) became newly colonized with FQREC. There was significant variability in regard to temporal changes in resistance mechanisms and levofloxacin MICs among isolates from individual patients. Compared to patients with transient colonization, patients with persistent colonization were more likely to have a urinary catheter (P=0.04), diarrhea (P=0.04), and a longer duration of hospitalization (22 and 9.0 mean days, respectively; P=0.01) prior to sampling. Our data demonstrate the significant variability of resistance mechanisms in colonizing E. coli isolates among hospitalized patients.

Ciprofloxacin Resistance Pattern Among Bacteria Isolated From Patients With Community-Acquired Urinary Tract Infection

“…Bacterial resistance can occur by different mechanisms: alterations of the cell permeability, changes in the site of action leading to loss of susceptibility to the antibiotic mediated by the increment of the efflux pump activity and by enzymatic degradation of the antibiotic 12 - 14 . Regarding fluoroquinolones, its resistance depends essentially on three factors: the ability to select resistant mutants; the ability to reach concentrations that are able to avoid the resistance selection; and the ability to act against mutant bacteria generated during previous treatments with other fluoroquinolones 15 , 16 .…”

Impact of Antibiotic Use during Hospitalization on the Development of Gastrointestinal Colonization with Escherichia coli with Reduced Fluoroquinolone Susceptibility

“…The mechanisms of resistance of these isolates have been previously described. 30 Finally, there was no evidence of clonal relatedness of the 73 unique FQREC isolates based on molecular typing by pulsed-field gel electrophoresis (PFGE).…”

Novel Pharmacokinetic/Pharmacodynamic Parameters Quantify the Exposure–Effect Relationship of Levofloxacin against Fluoroquinolone-Resistant Escherichia coli

“…Several studies investigated the impact of gyrA and parC mutations and qnr plasmids on phenotypic fluoroquinolone resistance, linking the level of phenotypic resistance to genomic properties of the investigated isolates solely with respect to MIC values [ 29 , 30 , 31 , 32 ]. In general, the MIC values were higher for a higher number of QRDR mutations.…”

“…Fluoroquinolone resistance mechanisms encompass mutations in the quinolone-resistance-determining regions (QRDR) of the target enzyme encoding genes gyrA and parC, and plasmid-mediated quinolone resistance, especially plasmids encoding for Qnr proteins [ 29 , 30 , 31 , 32 ]. Furthermore, altered membrane function affecting drug permeation contributes to reduced fluoroquinolone susceptibility, e.g., decreased expression of porin diffusion channels in Gram-negative bacteria or increased expression of efflux transporters [ 29 , 30 ].…”

“…Furthermore, altered membrane function affecting drug permeation contributes to reduced fluoroquinolone susceptibility, e.g., decreased expression of porin diffusion channels in Gram-negative bacteria or increased expression of efflux transporters [ 29 , 30 ]. The impact of genomic fluoroquinolone resistance mechanisms on phenotypic resistance is relatively well investigated [ 10 , 31 , 32 ], but clinical implications regarding fluoroquinolone dosing are missing.…”