IEEE Trans Ultrason Ferroelectr Freq Control. 2021 Sep;68(9):2965-2980. doi: 10.1109/TUFFC.2021.3077704. Epub 2021 Aug 27.
Urinary catheters often become contaminated with biofilms, resulting in catheter-associated urinary tract infections (CAUTIs) that adversely affect patient outcomes. Histotripsy is a noninvasive focused ultrasound therapy previously developed for the noninvasive ablation of cancerous tumors and soft tissues. Histotripsy has also previously shown the ability to treat biofilms on glass slides and surgical meshes. Here, we investigate the potential of histotripsy for the treatment of CAUTIs for the first time in vitro. Clinically relevant catheter materials (Tygon, Silicone, and latex catheter mimics) and commonly used clinical catheters were tested to determine the feasibility of producing luminal histotripsy bubble clouds. A Pseudomonas aeruginosa (strain PA14) biofilm model was developed and tested to produce luminal biofilms in an in vitro Tygon catheter mimic. This model was treated with histotripsy to determine the ability to remove a luminal biofilm. Finally, the bactericidal effects of histotripsy were tested by treating PA14 suspended inside the Tygon catheter mimic. Results showed that histotripsy produced precise luminal cavitation within all tested catheter mimics and clinical catheters. Histotripsy treatment of a PA14 biofilm with histotripsy reduced luminal biofilm OD590 signal down to background levels. Further, the treatment of suspended PA14 in Luria-Bertani (LB) showed a 3.45 ± 0.11 log reduction in CFU/mL after six histotripsy scans across the catheter mimics. Overall, the results of this study demonstrate the potential of histotripsy to provide a new modality for removing bacterial biofilms from catheter-based medical devices and suggest that additional work is warranted to investigate histotripsy for the treatment of CAUTIs and other biomaterial-associated infections.
导尿管常被生物膜污染，导致与导尿管相关的尿路感染（CAUTIs），从而对患者的预后产生不利影响。Histotripsy 是一种非侵入性的聚焦超声治疗方法，先前已开发用于非侵入性消融癌性肿瘤和软组织。Histotripsy 还以前显示出治疗玻璃幻灯片和手术网片上生物膜的能力。在这里，我们首次在体外研究了 Histotripsy 治疗 CAUTIs 的潜力。测试了临床上相关的导管材料（Tygon、Silicone 和乳胶导管模拟物）和常用的临床导管，以确定在管腔内产生 Histotripsy 气泡云的可行性。开发并测试了铜绿假单胞菌（PA14 株）生物膜模型，以在体外 Tygon 导管模拟物中产生管腔内生物膜。该模型用 Histotripsy 进行处理，以确定去除管腔内生物膜的能力。最后，通过处理 Tygon 导管模拟物内悬浮的 PA14 来测试 Histotripsy 的杀菌效果。结果表明，Histotripsy 在所有测试的导管模拟物和临床导管中都产生了精确的管腔空化。Histotripsy 处理 PA14 生物膜可将管腔生物膜 OD590 信号降低至背景水平。此外，在 LB 中处理悬浮的 PA14 时，经过六次 Histotripsy 扫描穿过导管模拟物后，CFU/mL 减少了 3.45±0.11 对数。总体而言，这项研究的结果表明 Histotripsy 有潜力提供一种从基于导管的医疗器械中去除细菌生物膜的新方法，并表明需要进一步研究 Histotripsy 治疗 CAUTIs 和其他与生物材料相关的感染的可能性。
