Activity of mecillinam against USA urinary tract clinical isolates from 2017 to 2020 including isolates resistant to comparator antibiotics

IF 3.7 3区医学 Q2 INFECTIOUS DISEASES Journal of global antimicrobial resistance Pub Date : 2024-09-13 DOI:10.1016/j.jgar.2024.08.013

Stephen Hawser , Ian Morrissey , Nimmi Kothari , Federica Monti , Anne Santerre Henriksen

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Abstract

Objectives

To support the clinical development of mecillinam and pivmecillinam in the United States for the treatment of complicated and uncomplicated urinary tract infections (UTIs), this study investigated the activity of mecillinam compared with other antibiotics against Enterobacterales isolates from patients with UTIs in the United States during 2017 to 2020. Mecillinam is a first-in-class amidinopenicillin antibiotic, being the only β-lactam to exert its antibacterial activity through exclusive binding to penicillin-binding protein 2. Pivmecillinam is the oral prodrug of mecillinam and is recommended as a first-line therapy by the Infectious Disease Society of America guidelines for uncomplicated UTIs and is approved for the treatment of uncomplicated UTIs in Europe, Canada, and the United States.

Methods

A total of 3303 isolates were collected and antimicrobial susceptibility determined according to Clinical Laboratory and Standards Institute (CLSI) guidelines.

Results

Susceptibility was highest for fosfomycin (97.1% susceptible) and mecillinam (94.9% susceptible). Against extended-spectrum beta-lactamase (ESBL)-positive bacteria susceptibilities were highest for mecillinam (98.2% susceptible) and fosfomycin (97.3% susceptible) and against ESBL-positive K. pneumoniae only mecillinam and fosfomycin had > 80% susceptibility. Resistance to comparator antibiotics was highest for trimethoprim-sulfamethoxazole (27.1%), followed by ciprofloxacin (19.3%), ceftriaxone (19.2%), and nitrofurantoin (12.1%). Multi-drug-resistant isolates were most susceptible to mecillinam and fosfomycin.

Conclusion

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美西林对 2017-2020 年美国尿路临床分离株的活性，包括对比较抗生素耐药的分离株。

研究目的为支持美西林和匹美西林在美国用于治疗复杂和非复杂性尿路感染的临床开发，本研究调查了 2017-2020 年期间美西林与其他抗生素相比对美国UTI 患者肠杆菌分离物的活性。美西林是第一类脒基青霉素类抗生素，是唯一通过与青霉素结合蛋白2独家结合而发挥抗菌活性的β-内酰胺类药物。Pivmecillinam是美西林的口服原药，被美国传染病学会指南推荐为治疗无并发症尿路感染的一线疗法，并在欧洲、加拿大和美国被批准用于治疗无并发症尿路感染：方法：共收集了 3303 个分离菌株，并根据 CLSI 指南测定其抗菌药敏感性：结果：对磷霉素（97.1% 易感）和美西林（94.9% 易感）的易感率最高。对广谱β-内酰胺酶（ESBL）阳性细菌的敏感性最高的是美西林（敏感性为98.2%）和磷霉素（敏感性为97.3%），而对ESBL阳性肺炎克氏菌的敏感性只有美西林和磷霉素大于80%。对比较抗生素耐药率最高的是三甲双胍-磺胺甲噁唑（27.1%），其次是环丙沙星（19.3%）、头孢曲松（19.2%）和硝基呋喃妥因（12.1%）。耐多药的分离株对美西林和磷霉素最敏感：这些数据进一步支持了美西林的临床开发和临床应用。

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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.