Department of Immunology and Microbiology, Copenhagen University, Copenhagen, Denmark.
Department of Front-End Innovation, Devices & Delivery Solutions, Novo Nordisk A/S, Hillerød, Denmark.
APMIS. 2022 Jul;130(7):404-416. doi: 10.1111/apm.13230. Epub 2022 May 17.
Needle reuse is a common practice and primary cause of customer compliance issues such as pain, bruising, clogging, injection site reactions (ISR), and associated lipodystrophy. This study aimed to characterize skin microflora at injection sites and establish microbial contamination of used pen injectors and needles. The second objective was to evaluate the risk of infections during typical and repeated subcutaneous injections. 50 participants with diabetes and 50 controls (n = 100) were sampled through tape strips and skin swabs on the abdomen and thigh for skin microflora. Used pen injectors and needles were collected after in-home use and from the hospital after drug administration by health care professionals (HCPs). Samples were analyzed by conventional culture, matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF), mass spectrometry (MS), confocal laser scanning microscopy (CLSM), and 16S/ITS high throughput sequencing (HTS). A mathematical model simulated the risk of needle contamination during injections. Injection site populations were in 10 cells/cm order, with increased viable bacteria and anaerobic bacteria on the skin in persons with diabetes (p = 0.05). Interpersonal variation dominated other factors such as sex or location. A higher prevalence of Staphylococcus aureus on abdominal skin was found in persons with diabetes than control skin (p ≤ 0.05). Most needles and cartridges (95% and 86%) contained no biological signal. The location of the device collection (hospital vs home-use) and use regimen did not affect contamination. CLSM revealed scarcely populated skin microflora scattered in aggregates, diplo, or single cells. Our mathematical model demonstrated that penetrating bacteria colonies during subcutaneous injection is unlikely. These findings clarify the lack of documented skin infections from subcutaneous insulin injections in research. Furthermore, these results can motivate the innovation and development of durable, reusable injection systems with pharmacoeconomic value and a simplified and enhanced user experience for patients.
针头重复使用是造成患者合规问题（如疼痛、瘀伤、堵塞、注射部位反应 (ISR) 和相关脂肪营养不良）的主要原因。本研究旨在对注射部位皮肤微生物群进行特征分析，并确定使用过的笔式注射器和针头的微生物污染情况。第二项研究目的是评估在典型和重复的皮下注射过程中感染的风险。通过对腹部和大腿进行胶带条和皮肤拭子取样，对 50 名糖尿病患者和 50 名对照者（n=100）进行采样，以了解皮肤微生物群。使用过的笔式注射器和针头在家庭使用后以及医护人员（HCPs）在医院给药后从 HCPs 处收集。使用传统培养、基质辅助激光解吸/电离飞行时间 (MALDI-TOF)、质谱 (MS)、共聚焦激光扫描显微镜 (CLSM) 和 16S/ITS 高通量测序 (HTS) 对样本进行分析。数学模型模拟了在注射过程中针头污染的风险。注射部位的菌群数量处于 10 个细胞/cm 的数量级，糖尿病患者的皮肤存在更多的活菌和厌氧菌（p=0.05）。人际间的变异性是影响因素中的主导因素，其他因素包括性别或位置。与对照皮肤相比，糖尿病患者腹部皮肤的金黄色葡萄球菌检出率更高（p≤0.05）。大多数针头和药筒（95%和 86%）不含生物信号。装置收集的位置（医院与家庭使用）和使用方案并不影响污染情况。CLSM 显示，皮肤微生物群稀疏地分布在聚集物、双球菌或单细胞中。我们的数学模型表明，在皮下注射过程中穿透细菌菌落的可能性不大。这些发现阐明了研究中未记录的皮下胰岛素注射引起皮肤感染的情况。此外，这些结果可以激励具有药物经济学价值的耐用、可重复使用的注射系统的创新和发展，为患者提供简化和增强的用户体验。
