What are the missing pieces needed to stop antibiotic resistance?

Abstract

As recognized by several international agencies, antibiotic resistance is nowadays one of the most relevant problems for human health. While this problem was alleviated with the introduction of new antibiotics into the market in the golden age of antimicrobial discovery, nowadays few antibiotics are in the pipeline. Under these circumstances, a deep understanding on the mechanisms of emergence, evolution and transmission of antibiotic resistance, as well as on the consequences for the bacterial physiology of acquiring resistance is needed to implement novel strategies, beyond the development of new antibiotics or the restriction in the use of current ones, to more efficiently treat infections. There are still several aspects in the field of antibiotic resistance that are not fully understood. In the current article, we make a non‐exhaustive critical review of some of them that we consider of special relevance, in the aim of presenting a snapshot of the studies that still need to be done to tackle antibiotic resistance.

Non-Canonical Aspects of Antibiotics and Antibiotic Resistance

“…The effects of antibiotics on bacteria in different growth stages, cell densities, and nutritional environments cannot be predicted by the MIC obtained in Mueller–Hinton broth with a standardized inoculum, nor can they reflect the actions of different drugs, despite having similar MICs. “The time has probably arrived to produce a more complex way of predicting the activity of an antibiotic on a bacterial population” [ 28 ].…”

“…This is perhaps a reminder that the biological phenomenon of AR responds mostly to selective pressure, but the prevalence of AR in pathogens causing infections is affected by societal factors as well. Furthermore, AR is often measured in ways that do not represent the actual prevalence (e.g., bias from mostly sampling patients already treated), and selection is only half of the driving force behind AR (and the one receiving the most attention), with transmission being the other, neglected, half [ 28 ]. In any case, more than simple “globalization”, increased migration from LMICs to other LMICs, as is often the case of refugees, and to HICs, in the case of migrant workers, amounts to tens or hundreds of millions of people, with AR carriage or infection around 25% [ 400 ], making the problem one without borders and impervious to local measures.…”