Department of Medical Microbiology, Ruhr-Universität Bochum, Universitätsstraße 150, 44801 Bochum, Germany.
J Antimicrob Chemother. 2018 Jun 1;73(6):1530-1536. doi: 10.1093/jac/dky084.
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.
某些肠杆菌科的染色体上编码 AmpCβ-内酰胺酶，导致高水平表达时对各种β-内酰胺类药物产生临床耐药性。在具有诱导型 AmpC 的 WT 细菌中，表达水平较低，但在β-内酰胺治疗期间可能会选择稳定的 AmpC 去阻遏突变体。因此，对于肠杆菌属、弗氏柠檬酸杆菌复合体、沙雷氏菌属和摩氏摩根菌，如果体外对氧肟头孢菌素敏感，EUCAST 专家规则建议抑制这些药物的敏感性测试结果，或注意不要单独使用这些药物，因为存在选择耐药性的风险。然而，临床观察表明，在具有诱导型 AmpC 的所有物种中，耐药性的出现并非同样普遍。
确定具有诱导型 AmpC 的肠杆菌科中 AmpC 去阻遏的种特异性突变率，该突变率比以前描述的突变频率更准确和可重复。
使用基于 Luria-Delbrück 波动分析的方案确定突变率。总共分析了 237 株分离株。
在阴沟肠杆菌复合体、产气肠杆菌、弗氏柠檬酸杆菌复合体和蜂房哈夫尼亚菌分离株中，突变率较高，平均突变率为 3×10-8。相比之下，普罗维登斯菌属、沙雷氏菌属和摩根摩根菌属的分离株的平均突变率要低得多。此外，我们还观察到 AmpC 去阻遏突变体的耐药模式存在种特异性差异。
我们的数据可能有助于预测不同具有诱导型 AmpC 的肠杆菌科感染患者使用氧肟头孢菌素治疗失败的风险。此外，我们提出了优化当前 EUCAST 专家规则的建议。
