Optimization of prophylactic antibacterial therapy in spinal surgery through mechanical PKPD modelling to reduce the emergence of antibiotic-resistant bacteria (OPATS-PKPD)

Antimicrobial resistance threatens human health, impacting critical medical procedures like surgeries. While spine-related issues contribute to global disability, spinal surgery offers a solution by enhancing patients\' quality of life and proving cost-effective. The current standard of care for intervertebral disc surgery involves administering prophylactic antibiotics, which has been demonstrated to reduce iatrogenic discitis. Pharmacokinetics and Pharmacodynamics (PK/PD) studies play a pivotal role in evaluating medicinal products and improving therapy, with population-based approaches aiding in understanding variability in drug safety and efficacy. However, current antibiotic therapy models often overlook crucial factors like drug local concentration and bacterial behavior. The project aims to develop mechanism-based PKPD models, combined with population PK and Monte Carlo simulation, to optimize cephazolin. This will be based on clinical data from patients, including plasma concentration time series and respective intervertebral disc concentrations of cephazolin in patients undergoing discectomy, potentially enhancing efficacy and safety while minimizing the probability of resistant strain isolation. Through the integration of active pharmaceutical ingredient pharmacokinetic, pharmacodynamic, mechanistic-based distribution, and microbiologic data, the PK-PD target attainment in the intervertebral disc will be characterized, and an optimized therapy protocol established.