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. 

Outcomes

• Original scientific articles published, submitted or accepted for publication in the Q1 or Q2 quartile publications included in Web of Science Core Collection or SCOPUS database - 2;
• Scientific databases and datasets developed within the project and prepared according to FAIR principles - 1;
• Project proposal submitted in an international call for research and development projects (competition abroad or submitted by an international consortium) - 1;
• Project proposal submitted in a Latvian call for research and development projects - 1;
• Doctoral thesis defended within the thematic focus of the project - 1;
• Other project results according to the specific nature of the project complementary to those listed above (including pre-prints) -1.

Project Research Team

• Project Manager: Sigita Kazūne,
• Egils Stalidzāns,
• Jānis Kurlovičs,
• Santa Niedra

Project-related activitie

Publications

• Repņikovs A., Briuks K., Paulausks A., Studers P., Logviss K., Mauriņa B., Bandere D., Kurlovičs J., Kazūne S. (2025). Impact of Intervertebral Disc Degeneration and Endplate Changes on Cefazolin Penetration into the Intervertebral Disc. Medicina (Kaunas), 61(11), Article 1999. (7 November 2025)
• Published in Proceedings of the Latvian Academy of Sciences. Section B: Natural, Exact, and Applied Sciences, Vol. 79, Issue 1–2 (April 2025):  
• Aukone M., Briuks K., Kazūne S., Repņikovs A. (2025). Adherence to Guidelines for Antibiotic Prophylaxis in Spine Surgery Patients
• Grundane S., Repņikovs A., Kazūne S., Briuks K., Bandere D., Paulausks A., Mazurs A. (2025). Cefazolin Concentration in Intervertebral Discs in Multilevel Spine Surgery

Conferences

• Participation in the 43rd Annual Meeting of the European Bone and Joint Infection Society (EBJIS), Bologna, Italy. Repņikovs A., Studers P., Bandere D., Briuks K., Paulausks A., Mazurs A. et al. presented Differential Effect of Modic Type Changes on Cefazolin Penetration into Intervertebral Discs During Single-Level Posterior Spinal Interbody Fusion. The work was presented during the Best Posters Session. (11–13 September 2025)
• Participation in the RSU International Research Conference on Medical and Health Care Sciences “Knowledge for Use in Practice”, Riga, Latvia. Repņikovs A., Studers P., Bandere D., Briuks K., Paulausks A., Mazurs A. et al. presented MODIC Type Endplate Changes as a Modifier for Cephazolin Penetration into the Intervertebral Disc. (26–28 March 2025)
  Conference Abstract Book
• Participation in The International Scientific Conference on Medicine and Health Sciences of the University of Latvia 2026, Riga, Latvia. Grundane S., Bandere D., Briuks K., Kazūne S., Paulausks A., Repņikovs A. presented Vancomycin Tissue Distribution in Intervertebral Discs in the Setting of Spinal Surgery. The abstract received 1st place in the abstract competition. (26 March 2026)
  Conference Abstract Book
• Participation in the international conference Contemporary Pharmacy: Issues, Challenges and Expectations 2026, Kaunas, Lithuania. Niedra S., Mazurs A., Kazūne S., Logviss K. presented Development and Validation of a Sensitive and Accurate Method for the Determination of Cefazolin in the Intervertebral Disc by UHPLC-HRMS. The abstract received 3rd place in the abstract competition. (27 March 2026)
• Participation in the 13th International Baltic Congress of Anaesthesiology and Intensive Care, Kaunas, Lithuania. Aukone M., Briuks K., Repņikovs A., Kazūne S. presented Adherence to Guidelines for Antibiotic Prophylaxis in Spine Surgery Patients. (18–20 September 2025)
• Participation in the 12th International Student Conference in Health and Social Sciences (ISC 2026), Riga, Latvia. Grundane S. presented the poster Vancomycin Penetration into Intervertebral Discs During Spine Surgery: A Population Pharmacokinetic Analysis. (26–27 March 2026)
  Conference Abstract Book  

Other Project Results

• A Data Management Plan was prepared for the implementation of the project Optimization of Prophylactic Antibacterial Therapy in Spinal Surgery Through Mechanical PKPD Modelling to Reduce the Emergence of Antibiotic-Resistant Bacteria (OPATS-PKPD). Author: Jānis Kurlovičs. (Q1 2025)
• Validation of the cefazolin analytical determination method (WP3) was completed for project purposes. Authors: Austris Mazurs and Konstantīns Logviss. (Q4 2025)
• A clinical study documentation package was developed, including the clinical study protocol, Manual of Operations, Case Report Form, and Ethics Committee approval for the implementation of the project's clinical activities. (Q2 2026)