In vitro efficacy of ceftazidime/avibactam and cefiderocol against multidrug-resistant Gram-negative uropathogens: insights into β-lactamase-mediated resistance in clinical isolates

IF 4.5 Q2 PHARMACOLOGY & PHARMACY

Future Journal of Pharmaceutical Sciences Pub Date : 2026-04-07 DOI:10.1186/s43094-026-00946-3

Mohamed A. Ibrahim, Hisham A. Abbas, Ghada H. Shaker, Ahmed M. El-Baz

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引用次数: 0

Abstract

Background

Urinary tract infections (UTIs) are among the most common bacterial infections in hospitalized patients, frequently caused by Gram-negative bacteria such as Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa. The increasing prevalence of multidrug-resistant (MDR) isolates, mainly those producing β-lactamases, presents a major therapeutic challenge. This study investigates the in vitro efficacy of ceftazidime–avibactam (CZA) and cefiderocol against MDR Gram-negative uropathogens.

Methods

A total of 110 Gram-negative uropathogens were included in this study. The isolates were re-identified using standard biochemical tests, and antimicrobial susceptibility was assessed via the disk diffusion method. Phenotypic and genotypic methods were performed to detect β-lactamase production in selected MDR isolates.

Results

Among the retrieved isolates, 89 (80.9%) were MDR. The highest MDR rates were observed in P. mirabilis (100%) and P. aeruginosa (91%), followed by K. pneumoniae (90%) and E. coli (66%). Most isolates showed high resistance to β-lactams, fluoroquinolones, and aminoglycosides. CZA showed variable activity, with the highest susceptibility in P. mirabilis (100%) and E. coli (68.1%), while resistance was significant in K. pneumoniae (83.3%) and P. aeruginosa (77.3%). Notably, cefiderocol exhibited strong in vitro activity against CZA- and carbapenem-resistant isolates, based on disk diffusion testing. Molecular analysis revealed high rates of ESBL and carbapenemase genes, particularly blaNDM-1, blaVIM-1, and blaOXA-48, among CZA-resistant isolates.

Conclusion

These findings highlight the alarming resistance to CZA among carbapenemase and MBL producers, emphasizing the urgent need for continuous surveillance. Conversely, cefiderocol demonstrated enhanced in vitro efficacy against highly resistant isolates.

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头孢他啶/阿维巴坦和头孢地罗对多重耐药革兰氏阴性尿路病原体的体外疗效：临床分离株β-内酰胺酶介导的耐药性的见解

尿路感染（uti）是住院患者中最常见的细菌感染之一，通常由革兰氏阴性菌引起，如大肠杆菌、肺炎克雷伯菌、奇异变形杆菌和铜绿假单胞菌。越来越多的耐多药（MDR）菌株，主要是那些产生β-内酰胺酶的菌株，对治疗提出了重大挑战。本研究探讨头孢他啶-阿维巴坦（CZA）和头孢地罗（cefiderocol）对耐多药革兰氏阴性泌尿系统病原体的体外疗效。方法收集革兰氏阴性尿路病原菌110例。采用标准生化试验对分离菌株进行重新鉴定，并采用纸片扩散法进行药敏评价。采用表型和基因型方法检测所选MDR菌株β-内酰胺酶的产生。结果89株（80.9%）为耐多药。耐多药率最高的是神奇假单胞菌（100%）和铜绿假单胞菌（91%），其次是肺炎克雷伯菌（90%）和大肠杆菌（66%）。大多数分离株对β-内酰胺类、氟喹诺酮类和氨基糖苷类具有高耐药性。CZA表现出不同的活性，对P. mirabilis（100%）和E. coli（68.1%）的敏感性最高，对肺炎克雷伯菌（83.3%）和P. aeruginosa（77.3%）的耐药性显著。值得注意的是，根据圆盘扩散试验，头孢地罗对CZA和碳青霉烯耐药菌株表现出很强的体外活性。分子分析显示，在cza耐药菌株中，ESBL和碳青霉烯酶基因的比例较高，尤其是blaNDM-1、blaVIM-1和blaOXA-48。结论碳青霉烯酶和MBL生产企业对CZA的耐药性令人担忧，迫切需要持续监测。相反，头孢地罗对高耐药菌株的体外疗效增强。

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

Future Journal of Pharmaceutical Sciences PHARMACOLOGY & PHARMACY-

自引率

0.00%

发文量

审稿时长

23 weeks

期刊介绍： Future Journal of Pharmaceutical Sciences (FJPS) is the official journal of the Future University in Egypt. It is a peer-reviewed, open access journal which publishes original research articles, review articles and case studies on all aspects of pharmaceutical sciences and technologies, pharmacy practice and related clinical aspects, and pharmacy education. The journal publishes articles covering developments in drug absorption and metabolism, pharmacokinetics and dynamics, drug delivery systems, drug targeting and nano-technology. It also covers development of new systems, methods and techniques in pharmacy education and practice. The scope of the journal also extends to cover advancements in toxicology, cell and molecular biology, biomedical research, clinical and pharmaceutical microbiology, pharmaceutical biotechnology, medicinal chemistry, phytochemistry and nutraceuticals.