Antimicrobial tolerance can promote the evolution of antimicrobial resistance even under combination drug treatments widely used and expected to prevent it from occurring, a new study in Science finds.
Researchers closely monitored the evolutionary trajectory of sequential isolates of life-threatening methicillin-resistant Staphylococcus aureus (MRSA) blood infections isolated from patients undergoing combination treatment for persistent MRSA blood infections.
They observed rapid emergence of tolerance in microbial populations that was followed by the development of resistance, despite combination antibiotic treatment.
According to the authors, once tolerance was established for just one of the antibiotic drugs, the benefits of using drug combinations were lost. Experiments using different classes of antibiotics (including vancomycin, rifampicin, and daptomycin) produced similar results.
Designing combination therapies that account for tolerance or persistence may be especially relevant for the treatment of tuberculosis, where tolerance has been suggested to be a major factor for survival of the pathogen and where the prevention of the de novo evolution of resistance in patients is crucial, the study authors noted.
“The generality of the mechanism by which tolerance promotes resistance suggests that it is relevant not only to de novo evolution of resistance by mutations but also to other mechanisms for acquiring resistance, such as horizontal gene transfer,” they added.