Hinnu Mariliis, Mets Toomas, Kerkez Ivana, Putrinš Marta, Kaldalu Niilo, Cathomen Gino, Pla Verge Marta, Cichocka Danuta, Sturm Alexander, Tenson Tanel
Institute of Technology, University of Tartu, Tartu, Estonia.
Resistell AG, Muttenz, Basel-Landschaft, Switzerland.
Microbiol Spectr. 2025 Jun 3;13(6):e0238524. doi: 10.1128/spectrum.02385-24. Epub 2025 Apr 24.
Invasive salmonellosis caused by subspecies affects millions of people every year, mostly children from low-income countries, and is associated with a high mortality rate. Azithromycin is used to treat invasive salmonellosis resistant to first-line drugs despite conflicting effective concentrations and achievable serum concentrations . As resistance levels to azithromycin are rising, we demonstrate that nanomotion technology, which is based on measuring changes in bacterial nanoscale movements, can be used for rapid phenotypic testing of 's susceptibility to azithromycin. Additionally, the use of nanomotion enabled the detection of the bactericidal effect. Nanomotion changes under various culture conditions correlated with susceptibility measured by minimum inhibitory concenctration (MIC) determination, colony-forming unit (CFU) counting, and fluorescent reporter-based estimates of intrabacterial azithromycin accumulation. Environmental conditions, both during azithromycin treatment and throughout the recovery period, significantly affect the antibacterial response to azithromycin. Azithromycin susceptibility in is detectable after only 2 h of treatment. This reflects the quick action of the antibiotic, which could be one of the contributing factors behind the clinical efficacy of azithromycin for treatment. Our study underscores the critical role of assay conditions, which greatly influenced both azithromycin efficacy and the test results.
Azithromycin is used as a last-resort antibiotic to treat life-threatening infections caused by , a high-priority pathogen according to the World Health Organization. Resistance levels to azithromycin are increasing, highlighting the need for rapid susceptibility testing. In this study, we demonstrate that nanomotion technology can detect azithromycin susceptibility in , suggesting its potential use for rapid resistance detection in clinical settings and its future use with azithromycin. Additionally, the study shows that nanomotion technology can be used for susceptibility and postantibiotic effect testing for various pathogens and antibacterials, including those generally regarded as bacteriostatic.
由该亚种引起的侵袭性沙门氏菌病每年影响数百万人,其中大多数是来自低收入国家的儿童,并且与高死亡率相关。尽管阿奇霉素的有效浓度和可达到的血清浓度存在矛盾,但它仍被用于治疗对一线药物耐药的侵袭性沙门氏菌病。随着对阿奇霉素的耐药水平不断上升,我们证明基于测量细菌纳米级运动变化的纳米运动技术可用于快速表型检测该亚种对阿奇霉素的敏感性。此外,纳米运动的使用能够检测杀菌效果。在各种培养条件下的纳米运动变化与通过最低抑菌浓度(MIC)测定、菌落形成单位(CFU)计数以及基于荧光报告基因的细菌内阿奇霉素积累估计所测得的敏感性相关。在阿奇霉素治疗期间以及整个恢复期的环境条件,均会显著影响对阿奇霉素的抗菌反应。仅在治疗2小时后即可检测到该亚种对阿奇霉素的敏感性。这反映了抗生素的快速作用,这可能是阿奇霉素治疗该亚种临床疗效的促成因素之一。我们的研究强调了检测条件的关键作用,其对阿奇霉素疗效和检测结果均有很大影响。
阿奇霉素被用作治疗由该亚种引起的危及生命感染的最后手段抗生素,该亚种是世界卫生组织认定的重点病原体。对阿奇霉素的耐药水平正在上升,凸显了快速药敏试验的必要性。在本研究中,我们证明纳米运动技术可检测该亚种对阿奇霉素的敏感性,表明其在临床环境中快速检测耐药性的潜在用途及其未来与阿奇霉素的联合应用。此外,该研究表明纳米运动技术可用于各种病原体和抗菌药物的药敏及抗生素后效应检测,包括那些通常被视为抑菌剂的药物。