Introduction

We characterized AmpC β-lactamase mutations that resulted in ceftolozane/tazobactam resistance in extensively drug-resistant (XDR) Pseudomonas aeruginosa isolates recovered from patients treated with this agent from June 2016 to December 2018.

Methods

Five pairs of ceftolozane/tazobactam susceptible/resistant P. aeruginosa XDR isolates were included among a total of 49 patients treated. Clonal relationship among isolates was first evaluated by pulsed-field gel electrophoresis (PFGE). Multilocus sequence typing (MLST) was further performed. AmpC mutations were investigated by PCR amplification of the blaPDC gene followed by sequencing.

Results

The ST175 high-risk clone was detected in four of the pairs of isolates and the ST1182 in the remaining one. All resistant isolates showed a mutation in AmpC: T96I in two of the isolates, and E247K, G183V, and a deletion of 19 amino acids (G229–E247) in the other three. The G183V mutation had not been described before. The five isolates resistant to ceftolozane/tazobactam showed cross-resistance to ceftazidime/avibactam and lower MICs of imipenem and piperacillin/tazobactam than the susceptible isolates.

Conclusions

Ceftolozane/tazobactam resistance was associated in all of the cases with AmpC mutations, including a novel mutation (G183V) not previously described. There is a vital need for surveillance and characterization of emerging ceftolozane/tazobactam resistance, in order to preserve this valuable antipseudomonal agent.

中文翻译：

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广泛耐药铜绿假单胞菌分离株的 AmpC β-内酰胺酶突变的表征，这些分离株在治疗期间对头孢唑烷/他唑巴坦产生耐药性。

介绍

我们在2016 年 6 月至 2018 年 12 月从接受该药物治疗的患者中回收的广泛耐药 (XDR)铜绿假单胞菌分离株中表征了导致头孢洛扎/他唑巴坦耐药的 AmpC β-内酰胺酶突变。

方法

五对头孢唑烷/他唑巴坦敏感/耐药铜绿假单胞菌XDR 分离株包括在总共 49 名接受治疗的患者中。首先通过脉冲场凝胶电泳 (PFGE) 评估分离株之间的克隆关系。进一步进行了多位点序列分型（MLST）。通过 bla PDC基因的 PCR 扩增然后测序来研究 AmpC 突变。

结果

在四对分离株中检测到 ST175 高风险克隆，在其余一对分离物中检测到 ST1182。所有耐药菌株均显示 AmpC 突变：其中两个菌株中为 T96I，以及 E247K、G183V，以及其他三个中 19 个氨基酸的缺失 (G229–E247)。G183V 突变以前没有被描述过。5 个对头孢洛扎/他唑巴坦耐药的分离株显示出对头孢他啶/阿维巴坦的交叉耐药性，并且亚胺培南和哌拉西林/他唑巴坦的 MIC 低于敏感分离株。

结论

在所有 AmpC 突变的病例中，头孢洛扎/他唑巴坦耐药都与包括一种以前未描述的新突变 (G183V) 相关。迫切需要监测和表征新出现的头孢噻吩/他唑巴坦耐药性，以保护这种有价值的抗假单胞菌药物。