A Pharmacodynamic Study of Aminoglycosides against Pathogenic E. coli through Monte Carlo Simulation.

Abstract

This research focuses on combating the increasing problem of antimicrobial resistance, especially in Escherichia coli (E. coli), by assessing the efficacy of aminoglycosides. The study specifically addresses the challenge of developing new therapeutic approaches by integrating experimental data with mathematical modeling to better understand the action of aminoglycosides. It involves testing various antibiotics like streptomycin (SMN), kanamycin (KMN), gentamicin (GMN), tobramycin (TMN), and amikacin (AKN) against the O157:H7 strain of E. coli. The study employs a pharmacodynamics (PD) model to analyze how different antibiotic concentrations affect bacterial growth, utilizing minimum inhibitory concentration (MIC) to gauge the effective bactericidal levels of the antibiotics. The study's approach involved transforming bacterial growth rates, as obtained from time-kill curve data, into logarithmic values. A model was then developed to correlate these log-transformed values with their respective responses. To generate additional data points, each value was systematically increased by an increment of 0.1. To simulate real-world variability and randomness in the data, a Gaussian scatter model, characterized by parameters like κ and EC50, was employed. The mathematical modeling was pivotal in uncovering the bactericidal properties of these antibiotics, indicating different PD MIC (zMIC) values for each (SMN: 1.22; KMN: 0.89; GMN: 0.21; TMN: 0.32; AKN: 0.13), which aligned with MIC values obtained through microdilution methods. This innovative blend of experimental and mathematical approaches in the study marks a significant advancement in formulating strategies to combat the growing threat of antimicrobial-resistant E. coli, offering a novel pathway to understand and tackle antimicrobial resistance more effectively.