Translation of evolutionary principles into antimicrobial treatment strategies
The DZIF working group “Translation of evolutionary principles into antimicrobial treatment strategies,” led by Hakim Boudrioua, will develop therapeutic strategies and diagnostic tools that integrate key evolutionary principles to combat antimicrobial resistance. The aim is to optimize single and combination treatment regimens against both susceptible and multi-drug resistant bacterial pathogens. This approach considers not only the antimicrobial efficacy of a given antibiotic but also its broader effects on bacterial fitness and the selective pressure that promotes the emergence and spread of antibiotic resistance. The working group uses complicated urinary tract infections (UTIs), particularly those caused by Escherichia coli, as a clinical use case to translate its findings into practice. Its vision is to enable personalized treatment for patients with UTIs that improves treatment efficacy while reducing adverse effects, such as disruption of the gut microbiome, and limiting the selective pressure for antibiotic resistance.
Urinary tract infections (UTIs) include any infection of the urethra, bladder, or kidneys. They affect around 400 million people yearly, Escherichia coli being the most common pathogen responsible for the infection.
Repeated courses of antibiotics for recurring UTIs can promote the emergence of resistance and the spread of multidrug-resistant strains. While antibiotic combinations have long been used to treat complicated infections caused by multidrug-resistant pathogens, their efficacy depends on the specific treatment conditions. Suboptimal combinations carry the risk of poor bacterial killing and increased resistance development.
The working group aims to integrate evolutionary principles into the in-depth assessment of both simultaneous and sequential antibiotic combinations. The first aim is to identify treatment protocols that enable rapid killing of pathogens while reducing the risk of resistance development. The second aim is to elucidate the molecular mechanisms that influence treatment efficacy and the potential for resistance development. Insights into these mechanisms could pave the way for new therapeutic approaches.
To translate the findings into clinical practice, the group plans to conduct observational studies involving outpatients and hospitalized patients with UTIs. These studies will investigate how resistance emerges during treatment and how the response to therapy evolves. In the long term, the group aims to develop personalized therapies that account for evolutionary processes, extending beyond UTIs. These therapies are intended to improve treatment efficacy, prevent resistance-related recurrence wherever possible, and preserve the long-term utility of antibiotics.
