New strategies for individualized and rational use of antibiotics in difficult-to-treat infections

Antibiotic overuse and misuse are main drivers of the emerging multidrug-resistant (MDR) bacteria. It has been estimated that as much as 50% of antibiotic prescriptions are inappropriate. Much of the last-resort antibiotics are used in hospitals where decisions on therapy for bacterial infections are typically complex due to underlying diseases, organ failures and other patient-specific factors. Digital decision support systems and stewardship interventions are needed to promote rational use of available drugs. Also, a shift from one-size-fits-all to individualized precision medicine in severe bacterial infections is required. This PhD project includes an international multicenter randomized trial where a smartphone app for digital decision support is developed and introduced using a stepped-wedge cluster design in hospitals in Uppsala, Geneva and Rotterdam.

A prospective multicenter national study is conducted to capture real-life data on how recently introduced antibiotics with activity against MDR pathogens are used. Clinical and microbiological outcomes including resistance development after 7 days of therapy is recorded and the bacterial isolates are collected for genotypic and phenotypic characterization as well as synergy testing for antibiotic combinations. Finally, a prospective multicenter national study is conducted to assess pharmacokinetics (PK) in patients with infective endocarditis who receive prolonged and high-dose beta-lactam treatments. The data will be used to develop a mathematical PK model that can simulate and predict optimal dosing in this patient group to ensure therapeutic effect but avoid toxicity.