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image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Journal of Antimicro...arrow_drop_down
image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
Journal of Antimicrobial Chemotherapy
Article . 2018 . Peer-reviewed
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Species-specific mutation rates for ampC derepression in Enterobacterales with chromosomally encoded inducible AmpC β-lactamase

Authors: Rebekka, Kohlmann; Tobias, Bähr; Sören G, Gatermann;

Species-specific mutation rates for ampC derepression in Enterobacterales with chromosomally encoded inducible AmpC β-lactamase

Abstract

AmpC β-lactamases are encoded on the chromosomes of certain Enterobacterales and lead to clinical resistance to various β-lactams in case of high-level expression. In WT bacteria with inducible AmpC, the expression is low, but selection of stably ampC-derepressed mutants may occur during β-lactam therapy. Thus, for Enterobacter spp., Citrobacter freundii complex, Serratia spp. and Morganella morganii that test susceptible in vitro to oxyimino-cephalosporins, the EUCAST expert rules recommend suppressing susceptibility testing results for these agents or noting that their use in monotherapy should be discouraged, owing to the risk of selecting resistance. However, clinical observations suggest that emergence of resistance is not equally common in all species with inducible AmpC.To determine species-specific mutation rates, which are more accurate and reproducible than previously described mutant frequencies, for ampC derepression in Enterobacterales with inducible AmpC.Mutation rates were determined using a protocol based on Luria-Delbrück fluctuation analyses. Overall, 237 isolates were analysed.Mutation rates were high in Enterobacter cloacae complex, Enterobacter aerogenes, C. freundii complex and Hafnia alvei isolates, with a mean mutation rate of 3 × 10-8. In contrast, mean mutation rates were considerably lower in Providencia spp., Serratia spp. and especially M. morganii isolates. Furthermore, we observed species-specific variations in the resistance patterns of ampC-derepressed mutants.Our data might help to predict the risk of treatment failure with oxyimino-cephalosporins in infections by different Enterobacterales with inducible AmpC. Moreover, we make a proposal for optimization of the current EUCAST expert rule.

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Keywords

Enterobacteriaceae Infections, Cefotaxime, Microbial Sensitivity Tests, Chromosomes, Bacterial, beta-Lactams, beta-Lactamases, Anti-Bacterial Agents, Bacterial Proteins, Enterobacteriaceae, Mutation Rate, Species Specificity

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
87
Top 1%
Top 10%
Top 10%
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