For complex infections in ICU settings, combination antimicrobial therapy is commonly used. However, current studies do not show differences in clinical outcomes or survival between empirical combination therapy and monotherapy in ICU patients with suspected or confirmed infections. Therefore, other factors that contribute to the poor outcomes of treatments should be considered. Some studies have found that poor prognosis and higher mortality rates in ICU patients are due to suboptimal exposure to antibiotics at standard dosages. A study conducted using DALI software, a software based on distance-matrix alignment that used to navigate, integrate and organize data pushed out by genomics and structural genomics, explored the relationship between clinical outcomes and pharmacokinetics of antimicrobials applied in critically ill patients (3). It found that that standard doses of β-lactams given to some patients in the ICU did not achieve 50 % fT > MIC (β-lactam PK/PD target value). Further, these patients were found to have a 32% lower likelihood of achieving positive clinical outcomes. To improve the prognosis of these patients, new approaches may need to be explored in favor of more individualized antibiotic dosing.
The DBS method in this study was validated including selectivity, carryover, precision (0.078–16.70%), accuracy (85.19–117.17%), matrix effect, recovery (46.51–114.15 %), linearity, and dilution integrity. Further, DBS and serum concentrations of two antibiotics were compared, with statistical analysis confirming good correlation (r > 0.97) between them. The DBS concentrations of the two available samples were significantly higher than the serum concentrations when vancomycin concentrations were greater than 15 μg/mL. However, further clinical samples may be required for validation.
Overall, this method provided a convenient means for sampling. This approach can be valuable in situations where traditional blood sampling methods are impractical or difficult to routinely perform.
References
(1) Qi, Z.; Zhang, S.; Li, J.; et al. LC-MS/MS Analysis of Five Antibiotics in Dried Blood Spots for Therapeutic Drug Monitoring of ICU Patients. J. Chromatogr. B 2025, 1263, 124699. DOI: 10.1016/j.jchromb.2025.124699
(2) Vincent, J-L.; Sakr, Y.; Singer, M.; et al. Prevalence and Outcomes of Infection Among Patients in Intensive Care Units in 2017. JAMA 2020, 323 (15), 1478–1487. DOI: 10.1001/jama.2020.2717
(3) Holm, L. DALI and the Persistence of Protein Shape. Protein Sci. 2020, 29 (1). 128–140. DOI: 10.1002/pro.3749
(4) Therapeutic Drug Monitoring. MedlinePlus 2024. https://medlineplus.gov/lab-tests/therapeutic-drug-monitoring/ (accessed 2025-6-27)