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阿曼复杂尿路感染患者及其感染源的抗菌药物耐药性图谱:表型和基因型见解

Mapping Antimicrobial Resistance in and from Complicated Urinary Tract Infections in Oman: Phenotypic and Genotypic Insights.

作者信息

Al Shizawi Nawal, Al Jabri Zaaima, Khan Fatima, Sami Hiba, Al Siyabi Turkiya, Al Muharrmi Zakariya, Sirasanagandla Srinivasa Rao, Rizvi Meher

机构信息

Department of Microbiology, Suhar Hospital, Ministry of Health, Sohar 100, Oman.

Department of Microbiology and Immunology, College of Medicine and Health Sciences, Sultan Qaboos University and Sultan Qaboos University Hospital, Muscat 123, Oman.

出版信息

Diagnostics (Basel). 2025 Apr 22;15(9):1062. doi: 10.3390/diagnostics15091062.

DOI:10.3390/diagnostics15091062
PMID:40361883
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12071653/
Abstract

Mapping the local etiology and susceptibility of common pathogens causing complicated urinary tract infection (cUTI) is important for promoting evidence-based antimicrobial prescribing. Evaluating the prevalence of extended-spectrum beta-lactamase (ESBL), AmpC beta-lactamase (AmpC), and carbapenemase-producing (CPEs) is equally important as it informs treatment guidelines and empiric management. Whole genome sequencing (WGS) enhances antimicrobial resistance (AMR) surveillance by complementing phenotypic antimicrobial susceptibility testing, offering deeper insights into resistance mechanisms, transmissions, and evolutions. Integrating it into routine AMR monitoring can significantly improve global efforts to combat antimicrobial resistance. Antimicrobial susceptibility profiles of isolates from cUTI were collected from patients presenting with Sultan Qaboos University Hospital, Muscat and Suhar Hospital, Suhar, Oman. Automated systems as well as manual methods were used for detection of ESBL, AmpC, and CPE. ESBLs, AmpC β-lactamases, and CPEs were further detected by manual methods: double-disk synergy test for ESBL; disk approximation assay and D69C AmpC detection set for AmpC, and mCIM and Combo test kit for CPE. WGS was carried out in 11 FOX-resistant and (22 carbapenem-resistant ) isolates with varying susceptibilities to identify circulating clades, AMR genes, and plasmids. Bioinformatic analysis was performed using online tools. The susceptibility patterns of from cUTI were as follows: nitrofurantoin (96%), fosfomycin (100%), fluoroquinolones (44%), aminoglycosides (93%), piperacillin-tazobactam (95%), and carbapenems (98%). In comparison, susceptibility rates of were far lower: nitrofurantoin (38%), fosfomycin (89%), aminoglycosides (82%), piperacillin-tazobactam (72%), and carbapenems (83%). however, was more susceptible to fluoroquinolones at 47% in comparison to The prevalence of ESBL among and was 37.2% and CRE was 6.2% while the estimated prevalence of AmpC was 5.4%. It was observed that was the predominant ESBL and AmpC producer, while was the major carbapenem-resistant (CREs) producer. No predominant multi-locus sequence typing (MLST) lineage was observed in AmpC-producing with nine MLST lineages being identified from eleven isolates: , , , , , , , and . On the other hand, a less diverse MLST spectrum (, , , and ) was observed in the CRE . Among the five MLST lineages, (twelve isolates) and (seven isolates) predominated. WGS revealed that was the predominant plasmid-mediated gene in , while and were the most common carbapenemase genes in . All -positive isolates co-harbored the quinolone resistance gene and the sulfonamide resistance gene while no aminoglycoside resistance genes were detected. The majority of CPE CRE carried other β-lactamase genes, such as , , and ; all co-harbored the quinolone resistance gene and 77% carried the aminoglycoside resistance gene . Our results suggest that fosfomycin is an excellent empiric choice for treating complicated cystitis caused by both and while nitrofurantoin is an appropriate choice for cystitis but not for . Aminoglycosides and piperacillin-tazobactam are excellent intravenous alternatives that spare carbapenems. was the predominant AmpC in while and were the predominant carbapenemases in . In AmpC-producing no MLST predominated, suggesting a significant flux in with lack of stable clades in this region. In contrast, and predominated in CRE suggesting a stable circulation of these in Oman. WGS profiling provides a deeper understanding of the genetic basis of resistance and enhances surveillance and offers comprehensive insights into pathogen evolution and transmission patterns.

摘要

明确引起复杂性尿路感染(cUTI)的常见病原体的局部病因及易感性,对于推动循证抗菌药物处方开具具有重要意义。评估超广谱β-内酰胺酶(ESBL)、AmpCβ-内酰胺酶(AmpC)和产碳青霉烯酶(CPE)的流行情况同样重要,因为这可为治疗指南和经验性治疗提供依据。全基因组测序(WGS)通过补充表型抗菌药物敏感性测试,增强了对抗菌药物耐药性(AMR)的监测,能更深入地洞察耐药机制、传播及演变情况。将其整合到常规AMR监测中,可显著提升全球对抗菌药物耐药性的应对能力。从阿曼马斯喀特的苏丹卡布斯大学医院和苏哈尔的苏哈尔医院就诊的患者中收集cUTI分离株的抗菌药物敏感性谱。采用自动化系统及手工方法检测ESBL、AmpC和CPE。通过手工方法进一步检测ESBL、AmpCβ-内酰胺酶和CPE:ESBL采用双纸片协同试验;AmpC采用纸片扩散试验和D69C AmpC检测试剂盒,CPE采用改良碳青霉烯灭活试验(mCIM)和组合检测试剂盒。对11株对FOX耐药及22株对碳青霉烯类耐药且敏感性各异的分离株进行WGS,以鉴定流行分支、AMR基因和质粒。使用在线工具进行生物信息学分析。cUTI分离株的药敏模式如下:呋喃妥因(96%)、磷霉素(100%)、氟喹诺酮类(44%)、氨基糖苷类(93%)、哌拉西林-他唑巴坦(95%)和碳青霉烯类(98%)。相比之下,[此处原文缺失相关内容]的药敏率则低得多:呋喃妥因(38%)、磷霉素(89%)、氨基糖苷类(82%)、哌拉西林-他唑巴坦(72%)和碳青霉烯类(83%)。然而,[此处原文缺失相关内容]对氟喹诺酮类的敏感性为47%,高于[此处原文缺失相关内容]。[此处原文缺失相关内容]和[此处原文缺失相关内容]中ESBL的流行率分别为37.2%和6.2%,而AmpC的估计流行率为5.4%。据观察,[此处原文缺失相关内容]是主要的ESBL和AmpC产生菌,而[此处原文缺失相关内容]是主要的耐碳青霉烯类[此处原文缺失相关内容](CREs)产生菌。在产AmpC的[此处原文缺失相关内容]中未观察到占主导地位的多位点序列分型(MLST)谱系,从11株分离株中鉴定出9种MLST谱系:[此处列举9种谱系名称,原文缺失]。另一方面,在CRE[此处原文缺失相关内容]中观察到的MLST谱系较少样化([此处列举4种谱系名称,原文缺失])。在这5种MLST谱系中,[此处列举两种谱系名称及对应株数,原文缺失](12株)和[此处列举一种谱系名称及对应株数,原文缺失](7株)占主导地位。WGS显示,[此处原文缺失相关内容]是[此处原文缺失相关内容]中主要的质粒介导[此处原文缺失相关内容]基因,而[此处列举两种基因名称,原文缺失]是[此处原文缺失相关内容]中最常见的碳青霉烯酶基因。所有[此处原文缺失相关内容]阳性分离株均同时携带喹诺酮耐药基因[此处原文缺失相关内容]和磺胺耐药基因[此处原文缺失相关内容],但未检测到氨基糖苷类耐药基因。大多数产CPE的CRE[此处原文缺失相关内容]携带其他β-内酰胺酶基因,如[此处列举三种基因名称,原文缺失];均同时携带喹诺酮耐药基因[此处原文缺失相关内容],77%携带氨基糖苷类耐药基因[此处原文缺失相关内容]。我们的结果表明,磷霉素是治疗由[此处原文缺失相关内容]和[此处原文缺失相关内容]引起的复杂性膀胱炎的极佳经验性选择,而呋喃妥因是治疗[此处原文缺失相关内容]膀胱炎的合适选择,但不适用于[此处原文缺失相关内容]。氨基糖苷类和哌拉西林-他唑巴坦是很好的静脉用药替代选择,可避免使用碳青霉烯类。[此处原文缺失相关内容]是[此处原文缺失相关内容]中主要的AmpC,而[此处列举两种碳青霉烯酶名称,原文缺失]是[此处原文缺失相关内容]中主要的碳青霉烯酶。在产AmpC的[此处原文缺失相关内容]中没有占主导地位的MLST,表明该地区[此处原文缺失相关内容]存在显著变化,缺乏稳定分支。相比之下,[此处列举两种谱系名称,原文缺失]在CRE[此处原文缺失相关内容]中占主导地位,表明它们在阿曼稳定传播。WGS分析能更深入地了解耐药的遗传基础,加强监测,并全面洞察病原体的进化和传播模式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a6c/12071653/0b6ec1d3e8a0/diagnostics-15-01062-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a6c/12071653/0b6ec1d3e8a0/diagnostics-15-01062-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a6c/12071653/0b6ec1d3e8a0/diagnostics-15-01062-g001.jpg

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