Division of Infectious Diseases, Department of Medicine, Mayo Clinic College of Medicine and Science, Rochester, Minnesota.
Department of Cardiovascular Diseases, Mayo Clinic College of Medicine and Science, Rochester, Minnesota.
Pacing Clin Electrophysiol. 2020 Mar;43(3):341-349. doi: 10.1111/pace.13888. Epub 2020 Mar 5.
Using synthetic antibiotic-eluting envelope (ABE) is an effective intervention for prevention of cardiovascular implantable electronic device (CIED) infection. The biologic extracellular-matrix envelope (ECME), may offer potential advantages over the synthetic ABE. To further minimize the risk of infection, the ECME can be hydrated in gentamicin prior to CIED implantation. We aimed to evaluate the efficacy and pharmacokinetics (PK) of gentamicin containing ECME in an animal model.
For all experiments, the ECME was hydrated in gentamicin (40 mg/Ml) (treatment) for 2 min. In vitro antimicrobial efficacy against six different bacterial species was assessed. In vivo experiments were conducted using a rabbit model of CIED pocket infection. Serum and ECM gentamicin concentrations were measured. Five different organisms were inoculated into the device pocket of control (ECME hydrated in 0.9% saline) and treatment groups. Macroscopic appearance and colony forming units from CIED, ECME, and tissue were determined.
No bacteria were recovered from any culture after 12 h of exposure to the gentamicin containing ECME. Serum gentamicin levels dropped below the limit of quantification at 15 h after implant. Gentamicin concentration in the ECME remained relatively stable for up to 7 days. Signs of clinical infection were observed in the control but not in the treatment group. In the presence of gentamicin, statistically significant reduction was demonstrated across all tested bacterial species.
In this preclinical animal infection model, gentamicin containing ECME was highly effective in reducing bacterial burden in the implant pocket, while systemic exposure after implantation remained low.
使用合成抗生素洗脱包膜（ABE）是预防心血管植入式电子设备（CIED）感染的有效干预措施。生物细胞外基质包膜（ECME）可能比合成 ABE 具有潜在优势。为了进一步降低感染风险，在植入 CIED 之前，ECME 可以用庆大霉素水化。我们旨在评估含有庆大霉素的 ECME 在动物模型中的疗效和药代动力学（PK）。
对于所有实验，ECME 均用庆大霉素（40mg/ml）（处理组）水化 2 分钟。评估了针对六种不同细菌的体外抗菌功效。使用兔 CIED 口袋感染模型进行了体内实验。测量血清和 ECM 中的庆大霉素浓度。将五种不同的生物体接种到对照（ECME 在 0.9%生理盐水）和处理组的设备口袋中。从 CIED、ECME 和组织中确定宏观外观和菌落形成单位。
在暴露于含有庆大霉素的 ECME 12 小时后，没有从任何培养物中回收任何细菌。植入后 15 小时，血清庆大霉素水平降至定量下限以下。ECME 中的庆大霉素浓度在 7 天内相对稳定。在对照组中观察到临床感染的迹象，但在处理组中没有。在庆大霉素存在的情况下，所有测试的细菌种类的细菌负荷均显著减少。
在这个临床前动物感染模型中，含有庆大霉素的 ECME 在降低植入袋中的细菌负荷方面非常有效，而植入后全身暴露仍然较低。
