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. 2024 Jan 10;16(1):94.
doi: 10.3390/pharmaceutics16010094.

Pharmacokinetic Interpretation of Applying Local Drug Delivery System for the Treatment of Deep Surgical Site Infection in the Spine

Ahmad Khalid Madadi  1 , Moon-Jun Sohn  1   2
Affiliations

Pharmacokinetic Interpretation of Applying Local Drug Delivery System for the Treatment of Deep Surgical Site Infection in the Spine

Ahmad Khalid Madadi et al. Pharmaceutics. .

Abstract

Surgical site infections (SSIs) after spinal surgery present significant challenges, including poor antibiotic penetration and biofilm formation on implants, leading to frequent treatment failures. Polymethylmethacrylate (PMMA) is widely used for localized drug delivery in bone infections, yet quantifying individual drug release kinetics is often impractical. This retrospective study analyzed 23 cases of deep SSIs (DSSIs) following spinal surgery treated with antibiotic-loaded PMMA. A mathematical model estimated personalized drug release kinetics from PMMA, considering disease types, pathogens, and various antibiotics. The study found that vancomycin (VAN), ceftriaxone (CRO), and ceftazidime (CAZ) reached peak concentrations of 15.43%, 15.42%, and 15.41%, respectively, within the first two days, which was followed by a lag phase (4.91-4.92%) on days 2-3. On days 5-7, concentrations stabilized, with CRO at 3.22% and CAZ/VAN between 3.63% and 3.65%, averaging 75.4 µg/cm2. Key factors influencing release kinetics include solubility, diffusivity, porosity, tortuosity, and bead diameter. Notably, a patient with a low glomerular filtration rate (ASA IV) was successfully treated with a shortened 9-day intravenous VAN regimen, avoiding systemic complications. This study affirms the effectiveness of local drug delivery systems (DDS) in treating DSSIs and underscores the value of mathematical modeling in determining drug release kinetics. Further research is essential to optimize release rates and durations and to mitigate risks of burst release and tissue toxicity.

Keywords: antibiotics-loaded bone cement; drug delivery system; drug release kinetic; mathematical model; polymethylmehthacrylate (PMMA); surgical site infection; sustained release.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Cumulative antibiotic release from a single PMMA bead. The differences in cumulative release between CRO vs. CAZ (53.3%), CRO vs. VAN (39.1%), and 1.5 cm diameter VAN over 1.0 cm diameter VAN (22.1%) were all statistically significant (p < 0.001, as determined by the one-way ANOVA test).
Figure 2
Figure 2
Daily antibiotic release from a single PMMA bead. Three distinct phases of daily release were observed during the first week (a), which are then followed by a consistent daily release pattern extending from day 8 to day 42 (b). The mean daily release rates over 42 days are 1.81% for VAN, 1.69% for CRO, 1.73% for CAZ, and 2.39% for VAN 1.5.
Figure 3
Figure 3
Impact of bead quantity on cumulative antibiotic release.
See this image and copyright information in PMC

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