Elitas Meltem, Kalayci Demir Guleser, Vural Kaymaz Sumeyra
Faculty of Engineering and Natural Sciences, Sabanci University, Istanbul 34956, Turkiye.
Faculty of Engineering, Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir 35397, Turkey.
ACS Omega. 2023 Oct 5;8(41):38452-38458. doi: 10.1021/acsomega.3c05233. eCollection 2023 Oct 17.
Antibiotic resistance is a global health threat. We urgently need better strategies to improve antibiotic use to combat antibiotic resistance. Currently, there are a limited number of antibiotics in the treatment repertoire of existing bacterial infections. Among them, rifampicin is a broad-spectrum antibiotic against various bacterial pathogens. However, during rifampicin exposure, the appearance of persisters or resisters decreases its efficacy. Hence, to benefit more from rifampicin, its current standard dosage might be reconsidered and explored using both computational tools and experimental or clinical studies. In this study, we present the mathematical relationship between the concentration of rifampicin and the growth and killing kinetics of cells. We generated time-killing curves of cells in the presence of 4, 16, and 32 μg/mL rifampicin exposures. We specifically focused on the oscillations with decreasing amplitude over time in the growth and killing kinetics of rifampicin-exposed cells. We propose the solution form of a second-order linear differential equation for a damped oscillator to represent the mathematical relationship. We applied a nonlinear curve fitting solver to time-killing curve data to obtain the model parameters. The results show a high fitting accuracy.
抗生素耐药性是对全球健康的一大威胁。我们迫切需要更好的策略来改善抗生素的使用，以对抗抗生素耐药性。目前，现有细菌感染的治疗药物中抗生素数量有限。其中，利福平是一种针对多种细菌病原体的广谱抗生素。然而，在接触利福平期间，持留菌或耐药菌的出现会降低其疗效。因此，为了从利福平中获得更多益处，可能需要重新考虑并利用计算工具以及实验或临床研究来探索其当前的标准剂量。在本研究中，我们展示了利福平浓度与细胞生长及杀灭动力学之间的数学关系。我们生成了在4、16和32μg/mL利福平暴露条件下细胞的时间杀灭曲线。我们特别关注了利福平暴露细胞生长和杀灭动力学中随时间振幅减小的振荡。我们提出了一个二阶线性微分方程的解形式来表示阻尼振荡器的数学关系，以描述上述关系。我们将非线性曲线拟合求解器应用于时间杀灭曲线数据以获得模型参数。结果显示拟合精度很高。
