Impact of vancomycin therapeutic drug monitoring on mortality in sepsis patients across different age groups: a propensity score-matched retrospective cohort study

Background: Due to its potent antibacterial activity, vancomycin is widely used in the treatment of sepsis. Therapeutic drug monitoring (TDM) can optimize personalized vancomycin dosing regimens, enhancing therapeutic efficacy and minimizing nephrotoxic risk, thereby potentially improving patient outcomes. However, it remains uncertain whether TDM affects the mortality rate among sepsis patients or whether age plays a role in this outcome.

Methods: We analyzed data from the Medical Information Mart of Intensive Care-IV database, focusing on sepsis patients who were admitted to the intensive care unit (ICU) and treated with vancomycin. The primary variable of interest was the use of vancomycin TDM during the ICU stay. The primary outcome was 30-day mortality. To control for potential confounding factors and evaluate associations, we used Cox proportional hazards regression and propensity score matching (PSM). Subgroup and sensitivity analyses were performed to assess the robustness of our findings. Furthermore, restricted cubic spline models were utilized to investigate the relationship between age and mortality among different groups of sepsis patients, to identify potential non-linear associations.

Results: A total of 14,053 sepsis patients met the study criteria, of whom 6,826 received at least one TDM during their ICU stay. After PSM, analysis of 4,329 matched pairs revealed a significantly lower 30-day mortality in the TDM group compared with the non-TDM group (23.3% vs.27.7%, p < 0.001). Multivariable Cox proportional hazards regression showed a significantly reduced 30-day mortality risk in the TDM group [adjusted hazard ratio (HR): 0.66; 95% confidence interval (CI): 0.61-0.71; p < 0.001]. This finding was supported by PSM-adjusted analysis (adjusted HR: 0.71; 95% CI: 0.66-0.77; p < 0.001) and inverse probability of treatment weighting analysis (adjusted HR: 0.72; 95% CI: 0.67-0.77; p < 0.001). Kaplan-Meier survival curves also indicated significantly higher 30-day survival in the TDM group (log-rank test, p < 0.0001). Subgroup analyses by gender, age, and race yielded consistent results. Patients with higher severity of illness-indicated by sequential organ failure assessment scores ≥6, acute physiology score III ≥40, or requiring renal replacement therapy, vasopressors, or mechanical ventilation-experienced more pronounced mortality improvement from vancomycin TDM compared with those with lower severity scores or not requiring these interventions. The results remained robust after excluding patients with ICU stays <48 h, those with methicillin-resistant Staphylococcus aureus infections, or when considering only patients with septic shock. In subgroup analyses, patients under 65 years (adjusted HR: 0.50; 95% CI: 0.43-0.58) benefited more from vancomycin TDM than those aged 65 years and older (adjusted HR: 0.75; 95% CI: 0.67-0.83). Notably, sepsis patients aged 18-50 years had the lowest mortality rate among all age groups, at 15.2% both before and after PSM. Furthermore, in this age group, vancomycin TDM was associated with a greater reduction in 30-day mortality risk, with adjusted HRs of 0.32 (95% CI: 0.24-0.41) before PSM and 0.30 (95% CI: 0.22-0.32) after PSM.

Conclusion: Vancomycin TDM is associated with reduced 30-day mortality in sepsis patients, with the most significant benefit observed in patients aged 18-50. This age group exhibited the lowest mortality rates and experienced the greatest reduction in mortality following TDM compared with older patients.