Prediction of antibiotic resistance: time for a new preclinical paradigm?

Abstract

Predicting the future is difficult, especially for evolutionary processes that are influenced by numerous unknown factors. Still, this is what is required of drug developers when they assess the risk of resistance arising against a new antibiotic candidate during preclinical development. In this Opinion article, we argue that the traditional procedures that are used for the prediction of antibiotic resistance today could be markedly improved by including a broader analysis of bacterial fitness, infection dynamics, horizontal gene transfer and other factors. This will lead to more informed preclinical decisions for continuing or discontinuing the development of drug candidates.

Prevalence of Multidrug-ResistantEscherichia coliIsolated from Drinking Water Sources

“…The emergence of antibiotic-resistant bacteria limits the clinical use of antibiotics and, as resistant bacteria become more prevalent, there is increasing concern that existing antibiotics will become ineffective against these pathogens and more expensive [2]. …”

In vivo Antibacterial Activity of Green Algae Ulva reticulata against Staphylococcus aureus in Drosophila Model of Infection

“…[1][2][3][4][5] To overcome this challenge, the discovery of new antibacterial drugs with a possible novel mechanism of action is urgently required. 6,7 Unfortunately, despite the huge effort given by countless research groups and pharmaceutical companies worldwide, the rate of discovery of new effective antibiotics is progressively declining, [7][8][9] which is substantially diminishing our hope of providing a solution to this ever-growing crisis.…”

Emerging issues in the environmental context of antibiotic-resistance

“…The conversion of sensitive bacteria to antibiotic resistance is influenced by the concentration of antibiotics to which bacterial popula tions are exposed, and the density of antibiotic-resistance genes present in the immediate environment (Sommer et al, 2017). The artificial introduction of antibiotics into the environment and natural ecosystems has the potential to tilt the balance of selection toward increased survival and proliferation of resistant bacteria, with potential impacts for humans and animals living in or near these ecosystems.…”