Department of Power Mechanical Engineering, National Tsing Hua University, Hsinchu, 30013, Taiwan.
Department of Laboratory Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, Kaohsiung, 83301, Taiwan.
Biosens Bioelectron. 2021 Mar 15;176:112890. doi: 10.1016/j.bios.2020.112890. Epub 2020 Dec 15.
This study reports an integrated microfluidic device that was capable of executing rapid antimicrobial susceptibility tests with one, two, or even three antibiotics against two clinically isolated multi-drug-resistant bacteria strains (including carbapenem-resistant Escherichia coli and methicillin-resistant Staphylococcus aureus). Bacteria were automatically mixed for 10 min with serially diluted antibiotics with a novel, membrane-type micromixer consisting of two circular micropumps, and the minimum inhibitory concentrations (MIC) were then determined via simple colorimetric reactions in only 4.5-6 h using only 3 μL of bacteria sample of each reaction (as opposed to 24 h and 50 μL, respectively, with the conventional broth micro-dilution method). In addition to determining MICs of antibiotics (ceftazidime, gentamicin, meropenem, vancomycin and linezolid), interaction effects across antibiotics combinations (gentamicin/meropenem or ceftazidime/gentamicin/meropenem) at different dosages were explored. The efficacy of polypharmacy showed additivity when gentamicin or ceftazidime/gentamicin were combined with meropenem to treat carbapenem-resistant Escherichia coli. This represents the first time that the perplexing clinical decision to choose multiple antibiotics for combination therapy against drug resistant bacteria can be realized on an integrated microfluidic device within 6 h.
本研究报告了一种集成微流控装置，该装置能够对两种临床分离的多药耐药菌（包括耐碳青霉烯类大肠杆菌和耐甲氧西林金黄色葡萄球菌）进行快速抗菌药敏试验，同时使用一种、两种甚至三种抗生素。细菌与连续稀释的抗生素在由两个圆形微泵组成的新型膜式微混合器中自动混合 10 分钟，然后仅通过简单的比色反应在 4.5-6 小时内即可确定最小抑菌浓度（MIC），而传统的肉汤微量稀释法分别需要 24 小时和 50 μL。除了测定抗生素（头孢他啶、庆大霉素、美罗培南、万古霉素和利奈唑胺）的 MIC 外，还探索了不同剂量下抗生素组合（庆大霉素/美罗培南或头孢他啶/庆大霉素/美罗培南）之间的相互作用效应。当庆大霉素或头孢他啶/庆大霉素与美罗培南联合治疗耐碳青霉烯类大肠杆菌时，多药联合疗法显示出相加作用。这是首次在 6 小时内，通过集成微流控装置实现了针对耐药菌的联合治疗中选择多种抗生素的复杂临床决策。
