Abstract
BackgroundAntibiotic resistance in bacterial infections is a growing threat to public health. Recent evidence shows that when exposed to stressful conditions, some bacteria perform higher rates of horizontal gene transfer and mutation, and thus acquire antibiotic resistance more rapidly.MethodsWe incorporate this new notion into a mathematical model for the emergence of antibiotic multi-resistance in a hospital setting.ResultsWe show that when stress has a considerable effect on genetic variation, the emergence of antibiotic resistance is dramatically affected. A strategy in which patients receive a combination of antibiotics (combining) is expected to facilitate the emergence of multi-resistant bacteria when genetic variation is stress-induced. The preference between a strategy in which one of two effective drugs is assigned randomly to each patient (mixing), and a strategy where only one drug is administered for a specific period of time (cycling) is determined by the resistance acquisition mechanisms. We discuss several features of the mechanisms by which stress affects variation and predict the conditions for success of different antibiotic treatment strategies.ConclusionsThese findings should encourage research on the mechanisms of stress-induced genetic variation and establish the importance of incorporating data about these mechanisms when considering antibiotic treatment strategies.
Highlights
Antibiotic resistance in bacterial infections is a growing threat to public health
Stress-induced mutation Considering stress-induced mutation, we define μs and μr as the rates of mutations conferring antibiotic resistance when bacteria are under antibiotic stress and when they are free of antibiotic stress, respectively
An important feature of antibiotic resistance is its persistence within a host without direct selective forces for long periods of time [38]
Summary
Antibiotic resistance in bacterial infections is a growing threat to public health. Recent evidence shows that when exposed to stressful conditions, some bacteria perform higher rates of horizontal gene transfer and mutation, and acquire antibiotic resistance more rapidly. A dangerous prospect of the continued evolution of drug resistance in bacteria is the creation of new, multidrug resistant bacteria Such bacterial strains are already present in several species of bacteria [3,6] and treating them is more difficult and often accompanied by a period of ineffective treatment, resulting in increased patient mortality [6]. Each patient receives a randomly selected drug This strategy can be viewed as the default antibiotic usage within a hospital unit, when there is no preference for any particular antibiotic. More antibiotics are used in combining than in mixing or cycling This could lead to higher antibiotic-related toxicity and increased treatment costs [11]
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