Department of Power Mechanical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan.
Laboratory Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, Kaohsiung 83301, Taiwan.
Lab Chip. 2019 Aug 21;19(16):2699-2708. doi: 10.1039/c9lc00585d. Epub 2019 Jul 22.
Polypharmacy is routinely administered to fight severe infections, though it has led to rampant multi-drug resistance in many bacterial strains. Preferably, antimicrobial susceptibility testing (AST) would be carried out prior to antibiotic prescription, though it is generally thought to be too complex and labor-intensive. In order to assist clinicians with better antibiotic administration for the effective treatment of bacterial infections, an integrated microfluidic system (IMS) capable of automating AST for 1-2 antibiotics against clinical bacterial pathogens was developed herein. Accurate determination of the minimum and fractional inhibitory concentrations of vancomycin, gentamicin, and linezolid were determined by assaying growth of two clinical methicillin-resistant Staphylococcus aureus isolates via a colorimetric assay on-chip. By applying various antibiotic combinations against a single pathogen in multiple chambers, the IMS could identify the optimal drug combination and the minimum effective dosage by evaluating the fractional inhibitory concentration index. This IMS possessed several advantages over conventional methods, including (1) a 50% reduction in bacterial sample and reagent volume (<50 μL per well), (2) less potential for human error due to its automatic nature, (3) faster liquid manipulation time by integrating the microfluidic components rather than labor-intensive process, and (4) straightforward result interpretation via colorimetric change instead of turbidity degree. Personalized medicine for treatment of bacterial infections may therefore be realized using this IMS.
常通过联合应用多种药物来治疗严重感染，但这导致许多细菌菌株出现了广泛的多重耐药性。虽然在开具抗生素处方之前最好进行抗菌药物敏感性测试（AST），但一般认为它过于复杂和耗费人力。为了帮助临床医生更好地管理抗生素，以有效治疗细菌感染，本文开发了一种能够自动进行针对临床细菌病原体的 1-2 种抗生素 AST 的集成微流控系统（IMS）。通过在芯片上进行比色测定，对两种临床耐甲氧西林金黄色葡萄球菌分离株的生长进行测定，准确确定了万古霉素、庆大霉素和利奈唑胺的最小和部分抑制浓度。通过在多个腔室内对单一病原体应用各种抗生素组合，IMS 可以通过评估部分抑制浓度指数来确定最佳药物组合和最小有效剂量。与传统方法相比，该 IMS 具有几个优势，包括（1）减少了 50%的细菌样本和试剂体积（每个孔<50 μL），（2）由于其自动化性质，减少了人为错误的可能性，（3）通过集成微流控组件而不是耗费人力的过程，缩短了液体处理时间，以及（4）通过比色变化而不是浊度程度，直接解释结果。因此，这种 IMS 可能会实现用于治疗细菌感染的个体化医学。
