Background: 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. Objectives: 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. Methods: Mutation rates were determined using a protocol based on Luria-Delbrück fluctuation analyses. Overall, 237 isolates were analysed. Results: 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. Conclusions: 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.
Background: 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. Objectives: 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. Methods: Mutation rates were determined using a protocol based on Luria-Delbrück fluctuation analyses. Overall, 237 isolates were analysed. Results: 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. Conclusions: 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.
Authors: Jacob E Lazarus; Alyson R Warr; Carole J Kuehl; Rachel T Giorgio; Brigid M Davis; Matthew K Waldor Journal: Appl Environ Microbiol Date: 2019-08-01 Impact factor: 4.792
Authors: Adam G Stewart; David L Paterson; Barnaby Young; David C Lye; Joshua S Davis; Kellie Schneider; Mesut Yilmaz; Rumeysa Dinleyici; Naomi Runnegar; Andrew Henderson; Sophia Archuleta; Shirin Kalimuddin; Brian M Forde; Mark D Chatfield; Michelle J Bauer; Jeffrey Lipman; Tiffany Harris-Brown; Patrick N A Harris Journal: Open Forum Infect Dis Date: 2021-08-02 Impact factor: 3.835
Authors: Olivia M Grünzweil; Lauren Palmer; Adriana Cabal; Michael P Szostak; Werner Ruppitsch; Christian Kornschober; Maciej Korus; Dusan Misic; Tanja Bernreiter-Hofer; Anna D J Korath; Andrea T Feßler; Franz Allerberger; Stefan Schwarz; Joachim Spergser; Elke Müller; Sascha D Braun; Stefan Monecke; Ralf Ehricht; Chris Walzer; Hrvoje Smodlaka; Igor Loncaric Journal: Int J Mol Sci Date: 2021-05-31 Impact factor: 5.923