Differential frequency of persister cells in clinically derived isolates of Pseudomonas aeruginosa after exposure to cefiderocol and ceftolozane/tazobactam.

IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Journal of Antimicrobial Chemotherapy Pub Date : 2024-10-24 DOI:10.1093/jac/dkae346
Aliaa Fouad, Samantha E Nicolau, Pranita D Tamma, Patricia J Simner, David P Nicolau, Christian M Gill
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Abstract

Background: Bacterial persistence is a phenomenon whereby a subpopulation of bacteria survive high concentrations of an active antibiotic in the absence of phenotypic alterations. Persisters are associated with chronic and recurrent infections for pathogens including Pseudomonas aeruginosa. Understanding persister profiles of newer antibiotics such as cefiderocol and ceftolozane/tazobactam against P. aeruginosa is warranted as these agents generally target difficult-to-treat infections.

Methods: Persister formation was assessed using in vitro assays against nine clinical P. aeruginosa isolates exposed to cefiderocol or ceftolozane/tazobactam. Quantitative persister assays were performed using a stationary phase of bacteria challenged with 10-fold MIC drug concentrations. Persisters were quantitated as the percent persisters at 24 h and the log ratio (LR) difference in AUC for cfu for each antibiotic alone compared with growth control. The tolerance disc test (TDtest) was used to qualitatively detect persisters.

Results: Percent persisters at 24 h was lower with cefiderocol compared with ceftolozane/tazobactam for six of the nine tested isolates. Eight of the nine isolates had higher reduction in LR for cefiderocol groups, suggesting an overall higher and more rapid bacterial reduction in cefiderocol groups. For cefiderocol, five of the nine tested isolates lacked regrowth after replacement with glucose disc, suggesting no persistence via the TDtest. For ceftolozane/tazobactam, three isolates lacked persister formation.

Conclusions: Cefiderocol resulted in less bacterial persistence relative to ceftolozane/tazobactam against nine clinical P. aeruginosa isolates. Cefiderocol's siderophore mechanism may be advantageous over ceftolozane/tazobactam through enhanced anti-persister effects. Clinical correlation of these findings is warranted as persisters can lead to antibiotic resistance and treatment failure.

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临床分离的铜绿假单胞菌在暴露于头孢克洛和头孢唑烷/他唑巴坦后,其宿主细胞的频率不同。
背景:细菌持久性是指细菌亚群在没有表型改变的情况下,在高浓度活性抗生素的作用下存活下来的现象。持久菌与包括铜绿假单胞菌在内的病原体的慢性和复发性感染有关。有必要了解头孢哌酮和头孢唑烷/他唑巴坦等新型抗生素针对铜绿假单胞菌的持久菌特征,因为这些药物通常针对难以治疗的感染:方法:针对暴露于头孢啶醇或头孢唑烷/他唑巴坦的九个临床铜绿假单胞菌分离物,采用体外试验评估了持久菌的形成。采用 10 倍 MIC 药物浓度的细菌静止期进行定量宿主检测。宿主定量为 24 小时后的宿主百分比,以及每种抗生素单独使用时与生长对照组相比的菌落总数 AUC 的对数比(LR)差异。耐受盘试验(TDtest)用于定性检测宿主:结果:与头孢唑烷/他唑巴坦相比,头孢啶醇对九种受试分离物中的六种分离物在 24 小时内的持续存在率较低。在 9 个分离株中,有 8 个在头孢得多合剂组中的 LR 减少率更高,这表明头孢得多合剂组的细菌减少率总体更高、更快。对于头孢羟氨苄,9 个受检分离物中有 5 个在更换为葡萄糖盘后没有再生长,这表明通过 TDtest 没有持久性。对于头孢洛赞/他唑巴坦,有三个分离物没有形成持久菌:结论:与头孢唑烷/他唑巴坦相比,头孢羟氨苄对九种临床铜绿假单胞菌分离物的细菌持久性更低。与头孢妥仑/他唑巴坦相比,Cefiderocol 的嗜肽机制可能通过增强抗芽孢杆菌作用而更具优势。由于顽固菌可导致抗生素耐药性和治疗失败,因此有必要将这些发现与临床相关联。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
9.20
自引率
5.80%
发文量
423
审稿时长
2-4 weeks
期刊介绍: The Journal publishes articles that further knowledge and advance the science and application of antimicrobial chemotherapy with antibiotics and antifungal, antiviral and antiprotozoal agents. The Journal publishes primarily in human medicine, and articles in veterinary medicine likely to have an impact on global health.
期刊最新文献
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