Is there a risk of overselling the microbiome? Is the world ready for personalized antibiotic therapy?
According to Tacconelli, clinical translation of scientific studies remains difficult, and antibiotic studies are no exception. Although there is enough evidence-based data available to reduce the negative effects on individual microbiomes from antibiotic treatments, this requires a strict adherence to the principles of antibiotic stewardship: choosing the right compound, dose, route of administration, and duration of treatment. However, many treating physicians lack the knowledge of the epidemiological, microbiological, clinical, and pharmacological principles of personalized antibiotic therapies available to patients. In addition, clinical guidelines are not yet established.
The other main limitation of microbiome studies are the difficulties of obtaining conclusive evidence due to the small sample sizes and the natural heterogeneity of the data. Co-administration of other antibiotics, previous antibiotic exposure or hospitalization, diverse age groups, and variable dosing regimens also complicate the data interpretation.
Tacconelli noted that for antibiotic treatment strategies, an individualized, translational approach is only possible if genetic and epigenetic studies are linked to clinical outcomes. Importantly, future research is required to determine the level of bacterial diversity that translates into treatment failures.
Investigators doing whole genome sequencing studies are at a risk of losing the connection to personalized medicine because they collect and analyze very large sets of data. In a clinical setting, data protection may be a limiting factor for effectiveness.
Finally, molecular-targeted treatments tend to be expensive as by definition they are suitable for only a limited number of patients. For drug development teams, Tacconelli cautioned that the dysbiotic potential should become a new parameter to consider when developing new antibiotics.
Question ‘Did you look at the baseline [microbiome] status of the patients in your studies?’
Tacconelli: ‘This is underway, and we hope this will be published shortly as a second follow-up study’