Effective antibiotic dosing in the presence of resistant strains

Abstract

Mathematical models can be very useful in determining efficient and successful antibiotic dosing regimens. In this study, we consider the problem of determining optimal antibiotic dosing when bacteria resistant to antibiotics are present in addition to susceptible bacteria. We consider two different models of resistance acquisition, both involve the horizontal transfer (HGT) of resistant genes from a resistant to a susceptible strain. Modeling studies on HGT and study of optimal antibiotic dosing protocols in the literature, have been mostly focused on transfer of resistant genes via conjugation, with few studies on HGT via transformation. We propose a deterministic ODE based model of resistance acquisition via transformation, followed by a model that takes into account resistance acquisition through conjugation. Using a numerical optimization algorithm to determine the ‘best’ antibiotic dosing strategy. To illustrate our optimization method, we first consider optimal dosing when all the bacteria are susceptible to the antibiotic. We then consider the case where resistant strains are present. We note that constant periodic dosing may not always succeed in eradicating the bacteria while an optimal dosing protocol is successful. We determine the optimal dosing strategy in two different scenarios: one where the total bacterial population is to be minimized, and the next where we want to minimize the bacterial population at the end of the dosing period. We observe that the optimal strategy in the first case involves high initial dosing with dose tapering as time goes on, while in the second case, the optimal dosing strategy is to increase the dosing at the beginning of the dose cycles followed by a possible dose tapering. As a follow up study we intend to look at models where ‘persistent’ bacteria may be present in additional to resistant and susceptible strain and determine the optimal dosing protocols in this case.

Current examining methods and mathematical models of horizontal transfer of antibiotic resistance genes in the environment

“…The mathematical model primarily achieves two objectives. Firstly, mathematical models can be applied in the context of public health environments, that set against the backdrop of clinical medical environments are significant for designing effective antibiotic dosing regimens or developing drugs related to clinical infections ( Roberts et al, 2021 ; Ali et al, 2022 ). Secondly, mathematical models set against real-world environments can assess and predict transfer dynamics under various influencing factors.…”

“…This was the first transformation dynamics model, successfully predicting the natural transformation frequencies of tetracycline resistance genes in both motile and non-motile strains of Azotobacter vinelandii . Asgher et al extended the aforementioned model by incorporating additional process pathways, such as variations in nutrient concentration, alterations in the density of susceptible bacterial population and changes in the extracellular DNA density in response to the population of antibiotic resistant and susceptible bacteria, thereby enhancing the capacity to better capture the underlying dynamics ( Ali et al, 2022 ).…”

Assessment of Antimicrobial Consumption in Multi-Field Hospitals with Pediatric Inpatients: Conventional vs. Novel Pediatric-Adjusted Methodologies

“…For each AM and considering the route of administration, the dose per growth unit was extracted from the national summaries of product characteristics (SmPC) [26]. If the dosing range was provided in the document, the dose was chosen based on the experts' opinions (clinical pharmacologists, pediatricians, and infectious disease specialists who routinely administer AMs to children in clinical practice), with a tendency to use moderate-to-higher doses to correspond the current resistance progression [27,28]. The following standard dosing approaches were considered according to SmPCs (Supplementary Table S20):…”

Molecular identification and probiotic potential characterization of lactic acid bacteria isolated from the pigs with superior immune responses

“…In recent decades, the growing need for livestock products, which necessitates growth promotion and disease prevention, has resulted in the extensive utilization of antibiotics as feed additives for animals (Zhang et al, 2022). The frequent and excessive use of antibiotics has led to the increased incidence of bacterial resistance (Ali et al, 2022). Antibiotic resistance is a global issue and poses a significant threat to the health of both humans and animals (Mehdi et al, 2018).…”