Epidemiology of aminoglycosides resistance and phenotypic detection of aac(6’)-Ib-cr gene in ESBL-producing Enterobacterales in febrile urinary tract infection in children

IF 3.2 3区医学 Q2 INFECTIOUS DISEASES

Journal of global antimicrobial resistance Pub Date : 2025-06-19 DOI:10.1016/j.jgar.2025.06.008

Audrey Baron , Fouad Madhi , Philippe Bidet , Corinne Levy , Robert Cohen , Yasmine Benhadid-Brahmi , Camille Jung , Elsa Sobral , Kevin La , Stéphane Bonacorsi , André Birgy

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引用次数: 0

Abstract

Objectives

ESBL-producing Enterobacterales (ESBL-E) poses a growing challenge in managing febrile urinary tract infections (FUTIs) in children, leaving amikacin as a good probabilistic once-daily and outpatient treatment option. This epidemiological study investigates aminoglycoside resistance patterns among pediatric ESBL-E isolates, with a particular focus on the aac(6’)-Ib-cr gene—a common resistance determinant that elevates amikacin MICs and may compromise its efficacy. We also aimed to evaluate a phenotypic method to detect aac(6’)-Ib-cr in clinical practice.

Methods

We studied 251 ESBL-E from pediatric FUTIs collected in 24 centers. All underwent whole-genome sequencing to determine aminoglycoside resistance genes. Antimicrobial susceptibility was determined by disk diffusion and E-test. Amikacin MICs were measured at standard (10^5 CFU/mL) and high (10^7 CFU/mL) inocula, and interpreted according to EUCAST 2024 breakpoints.

Results

Clinically relevant aminoglycoside-resistance genes were identified in 54.2% of isolates, although only 3.6% were resistant to amikacin. Among the isolates, 31.1% (78/251) carried aac(6’)-Ib-cr, co-occurring with other aminoglycoside-resistance genes in 94.9% of cases. Strains harboring aac(6’)-Ib-cr displayed higher amikacin MICs (median 8 mg/L vs 2 mg/L; p<0.001) and became resistant at high inoculum. We propose a simple phenotypic algorithm combining “cliff-like” amikacin inhibition-zone edges and tobramycin disk diameters (<16 mm), correctly identifying 99% of our aac(6’)-Ib-cr-positive strains.

Conclusion

The low amikacin resistance in ESBL-E supports its continued use as a reliable empiric treatment for pediatric FUTIs. However, the aac(6’)-Ib-cr gene can raise amikacin MICs, potentially compromising efficacy in high-inoculum infections despite EUCAST susceptibility. Our phenotypic algorithm helps detect it and guide treatment decisions for pediatric FUTIs.

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发热性尿路感染患儿产esbl肠杆菌氨基糖苷类耐药流行病学及aac（6’）-Ib-cr基因表型检测

目的：产esbl肠杆菌（ESBL-E）在管理儿童发热性尿路感染（FUTIs）方面提出了越来越大的挑战，使得阿米卡星成为一个很好的概率每日一次和门诊治疗选择。本流行病学研究调查了儿童ESBL-E分离株的氨基糖苷耐药模式，特别关注aac(6')-Ib-cr基因，这是一种常见的耐药决定因素，可提高阿米卡星mic并可能损害其疗效。我们还旨在评估在临床实践中检测aac（6’）-Ib-cr的表型方法。方法：对来自24个中心的251例小儿FUTIs患者的ESBL-E进行研究。所有患者均进行全基因组测序以确定氨基糖苷抗性基因。采用纸片扩散法和e -试验测定药敏。在标准（10^5 CFU/mL）和高（10^7 CFU/mL）接种时测定阿米卡星mic，并根据EUCAST 2024断点进行解释。结果：54.2%的分离株中检出与临床相关的氨基糖苷类耐药基因，但仅有3.6%的分离株对阿米卡星耐药。其中31.1%（78/251）的菌株携带aac（6’）-Ib-cr， 94.9%的菌株与其他氨基糖苷耐药基因共存。含有aac(6')-Ib-cr的菌株显示出更高的阿米卡星mic(中位数为8 mg/L vs 2 mg/L；结论：ESBL-E对阿米卡星的低耐药性支持其继续作为儿童FUTIs的可靠经验性治疗。然而，aac（6’）-Ib-cr基因可以提高阿米卡星mic，尽管EUCAST易感性，但可能会影响高接种量感染的疗效。我们的表型算法有助于检测它并指导儿科FUTIs的治疗决策。

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

Journal of global antimicrobial resistance INFECTIOUS DISEASES-PHARMACOLOGY & PHARMACY

CiteScore

8.70

自引率

2.20%

发文量

285

审稿时长

34 weeks

期刊介绍： The Journal of Global Antimicrobial Resistance (JGAR) is a quarterly online journal run by an international Editorial Board that focuses on the global spread of antibiotic-resistant microbes. JGAR is a dedicated journal for all professionals working in research, health care, the environment and animal infection control, aiming to track the resistance threat worldwide and provides a single voice devoted to antimicrobial resistance (AMR). Featuring peer-reviewed and up to date research articles, reviews, short notes and hot topics JGAR covers the key topics related to antibacterial, antiviral, antifungal and antiparasitic resistance.