Fluoroquinolone-selected resistance among Pseudomonas aeruginosa: impact on susceptibility to imipenem, ertapenem and meropenem
Abstract number: 902_p679
Fluoroquinolone-selected mutants of Pseudomonas aeruginosa can exhibit significant changes in carbapenem susceptibility. However, little is known about which fluoroquinolones are more likely to select for carbapenem resistance. This study assessed the occurrence and mechanism(s) of altered carbapenem susceptibility among P. aeruginosa mutants selected with levofloxacin and ciprofloxacin.
Pseudomonas aeruginosa PAO1 and a clinical isolate P. aeruginosa 164 were the parent strains, and single-step mutants were selected in-agar with 1X4X MIC of ciprofloxacin and levofloxacin. Confirmed mutants were evaluated for changes in susceptibility to imipenem, ertapenem and meropenem. Mutants with significant changes in carbapenem susceptibility were evaluated for changes in transcriptional expression of four efflux pumps and oprD.
Fifty-six confirmed fluoroquinolone-resistant mutants were selected, with none exhibiting decreases in imipenem susceptibility or changes in expression of mexEF-oprN. In contrast, four mutants demonstrated significantly decreased susceptibility to meropenem and ertapenem. However, these four mutants did not alter their expression of the four efflux pumps or oprD, and they were selected with both fluoroquinolones from both parent strains. The small numbers prevented meaningful comparisons between the fluoroquinolones. Three additional mutants exhibited hypersusceptibility to imipenem and ertapenem, with associated six- to 11-fold overexpression of mexCD-oprJ. One of these mutants was hypersusceptible to all three carbapenems, and meropenem hypersusceptibility was associated with fourfold decreased mexAB-oprM expression.
Ciprofloxacin and levofloxacin exhibited a propensity to select for both dual resistances to fluoroquinolones and meropenem/ertapenem, as well as carbapenem hypersusceptibility. The mechanism(s) of meropenem and ertapenem resistance remain unknown and warrant further investigation. Furthermore, similar studies using in vitro pharmacodynamic models should be conducted to determine if pharmacokinetically relevant exposure to levofloxacin and ciprofloxacin provides different selection pressures for mutant selection compared the static conditions used in this study."
|Session name:||XXIst ISTH Congress|
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