We're exploring how therapeutic drug monitoring (TDM) could be optimally performed for antibiotic combinations with a focus on associations of ?-lactam/?-lactamase inhibitor. In this work we compute the overall probability of target attainment (PTA) at the site of infection: for example PTA for the ?-lactam alone, PTA for the ?-lactamase inhibitor and PTA for the combo.
In order to compute PTA at the different sites of infection we need penetration ratios from the literature.
We found a way around that, which would require us to calculate tissue-to-plasma partition coefficient (Kp) for each organ, for each drug (through the use of Physiology-Based PK, PBPK).
The project would involve collection of PK parameters and values from the literature for each drug of each combo (ceftazidime-avibactam, ceftolozane-tazobactam, imipenem-relebactam, meropenem-vaborbactam and piperacillin-tazobactam) and once all parameters required are known: use a PBPK model to compute the different Kp coefficients. These parameters would later use in our PTA simulations.