In vitro activity of ceftolozane/tazobactam against Pseudomonas aeruginosa and Enterobacterales isolates collected from two general hospitals in Singapore

IF 4.9 2区 医学 Q1 INFECTIOUS DISEASES
Zhong Yang , Tze-Peng Lim , Nurhayati Binte Mohamed Yusoff , Crystal Shie Lyeen Wong , James Heng-Chiak Sim , Andrea L. Kwa
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引用次数: 0

Abstract

The emerging resistance to cephalosporins and carbapenems in gram-negative pathogens poses significant health challenges and increased treatment failures. The development and evaluation of novel therapeutic options are needed urgently. This study aimed to assess the in vitro activity of ceftolozane/tazobactam (C/T), a new cephalosporin and β-lactamase inhibitor combination, against isolates of Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae from different infection sources in two general hospitals in Singapore. Susceptibility testing revealed that C/T has good activity against 600 tested gram-negative pathogens, showing a 94.8% susceptibility rate across different species and infection types. Additionally, emergence of C/T resistance was also observed and characterized with whole genome sequencing (WGS) analysis. WGS analysis indicated that C/T resistance was predominantly associated with harbouring broad-spectrum β-lactamases such as carbapenemases, ESBLs, AmpC and others. Novel mutations in penicillin-binding-protein 3 (PBP3), the target of ceftolozane, and variants associated with hyper ampC expression (ampD, ampR, and dacB), were also found in C/T-resistant isolates, potentially contributing to C/T resistance. The finding of this study provides valuable local data on C/T susceptibility, which is important for guiding the proper clinical use of C/T and promoting antimicrobial stewardship in managing Gram-negative infections.
头孢唑烷/他唑巴坦对新加坡两所综合医院铜绿假单胞菌和肠杆菌分离株的体外活性研究
革兰氏阴性病原体中新出现的对头孢菌素和碳青霉烯类药物的耐药性构成了重大的健康挑战,并增加了治疗失败。迫切需要开发和评估新的治疗方案。本研究旨在评估头孢菌素/他唑巴坦(C/T)(一种新型头孢菌素和β-内酰胺酶抑制剂组合)对新加坡两家综合医院不同感染源的铜绿假单胞菌、大肠埃希菌和肺炎克雷伯菌的体外活性。药敏试验结果显示,C/T对600种革兰氏阴性病原菌具有良好的抗感染活性,对不同菌种和感染类型的敏感性为94.8%。此外,还观察到C/T耐药性的出现,并通过全基因组测序(WGS)分析进行了表征。WGS分析表明,C/T耐药主要与含有广谱β-内酰胺酶(如碳青霉烯酶、ESBLs、AmpC等)有关。在C/T耐药菌株中也发现了青霉素结合蛋白3 (PBP3)的新突变,以及与ampC高表达相关的变异(ampD, ampR和dacB),这可能有助于C/T耐药。本研究的发现提供了有价值的当地C/T敏感性数据,这对于指导临床正确使用C/T和促进革兰氏阴性感染的抗菌药物管理具有重要意义。
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来源期刊
CiteScore
21.60
自引率
0.90%
发文量
176
审稿时长
36 days
期刊介绍: The International Journal of Antimicrobial Agents is a peer-reviewed publication offering comprehensive and current reference information on the physical, pharmacological, in vitro, and clinical properties of individual antimicrobial agents, covering antiviral, antiparasitic, antibacterial, and antifungal agents. The journal not only communicates new trends and developments through authoritative review articles but also addresses the critical issue of antimicrobial resistance, both in hospital and community settings. Published content includes solicited reviews by leading experts and high-quality original research papers in the specified fields.
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