Integrating pharmacological modelling with conventional microbiology to improve predictions of drug efficacy and emergence of antimicrobial drug resistance.
Antibiotic resistance is a global problem on a scale that threatens the future of modern medicine. This has been highlighted by the World Health Organization and, in the UK, by the Chief Medical Officer for England and by the Department of Health.
Research to understand the consequences of adequate and inadequate prescribing can help improve the activity of existing antibiotics and mitigate the spread of resistance. Patients with severe (suspected) bacterial infections admitted to Intensive Care Units (ICU) often receive a standard antibiotic combination therapy during the initial treatment phase till susceptibility results have become available.
Administration of anti-infective treatment combinations tends to be a result of empirical practise supported by expert opinions and there is little rationale for drug combination choices and dosing. The increased prevalence of Multidrug-resistant Gram-negative organisms (MDRGNs) calls for detailed research to understand the consequences of direct versus delayed targeted treatment.
The proposed project enables comprehensive evaluation of untested doses by computer simulations and thereby supports rational drug and dose selection which can serve as the base for future antimicrobial drug combination research, facilitating an all-inclusive understanding of underlying mechanisms of drug action, pharmacodynamic drug-drug interactions and the impact of direct versus delayed treatment.