Eradication of Microorganisms Embedding in Biofilm by a Dose-Dependent Urokinase-Based Catheter Lock Solution in Chronic Hemodialysis Patients
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Jiayi Wang1, Xiaofei Peng2, Wenqing Yin1
1Department of Nephrology, The Second Xiangya Hospital, Central South University, Key Lab of Kidney Disease and Blood Purification in Hunan, Changsha, China.
Insights
Urokinase plasminogen activator (uPA)-based antibiotic lock therapy effectively removes biofilm-forming bacteria from central vein catheters in hemodialysis patients. This uPA-based approach demonstrates safety and superior efficacy in treating catheter-related blood stream infections compared to heparin-based therapy.
Area of Science:
- Nephrology
- Infectious Diseases
- Biotechnology
Background:
- Catheter-related blood stream infection (CRBSI) is a major complication in hemodialysis (HD) patients, associated with significant morbidity and mortality.
- Antibiotic lock therapy (ABL) is a key treatment for salvaging central vein catheters (CVCs) in CRBSI cases.
- Urokinase plasminogen activator (uPA)-based ABL offers potential antimicrobial and biofilm-degrading properties for CRBSI treatment.
Purpose of the Study:
- To evaluate the in vitro effectiveness of uPA-based ABL against microorganisms within biofilms.
- To assess the in vivo catheter salvage rate in HD patients with CRBSI using uPA-based ABL.
Main Methods:
- In vitro: Biofilm formation on HD catheters was induced; uPA with/without antibiotics was applied to assess antimicrobial and biofilm removal.
- In vivo: 86 HD patients with CRBSI were retrospectively analyzed, comparing uPA-based ABL to heparin-based ABL for catheter salvage.
Main Results:
- uPA demonstrated efficacy against Staphylococcus epidermidis biofilms, with limited regrowth observed.
- The combination of uPA and antibiotics showed superior antimicrobial and antibiofilm activity in vitro and in vivo compared to uPA alone or heparin-based ABL.
- uPA-based ABL was safe in HD patients and more effective for coagulase-negative Staphylococci related CRBSI.
Conclusions:
- Combined uPA and antibiotics effectively eradicate coagulase-negative S. epidermidis biofilms in vitro.
- uPA-based ABL is a safe and effective therapeutic option for CRBSI in HD patients, outperforming heparin-based ABL.
Introduction:
Catheter-related blood stream infection (CRBSI), the most common complication of central vein catheter (CVC), was closely associated with high morbidity and mortality in hemodialysis (HD) patients. Conjunction with systemic antibiotic, antibiotic lock (ABL) is an important therapeutic option to salvage the catheter. With extra antimicrobial and biofilm removing properties, urokinase plasminogen activator (uPA)-based ABL could have a potential role in the treatment of CRBSI.
Objective:
In this study, we aimed to explore effectiveness of uPA-based (ABL) on microorganisms embedded in biofilms in vitro and CVC salvage rate in HD patients with CRBSI.
Methods:
In vitro, we induced biofilms formation on the surface of HD catheter by mimicking the development of CRBSI. Applying uPA with or without antibiotics on the kinds of microorganism biofilms to explore its antimicrobial and biofilm removing properties. In vivo, 86 HD patients diagnosed as CRBSI were retrospectively enrolled to see effectiveness of uPA-based ABL on catheter salvage rate as compare to heparin-based ABL.
Results:
uPA was effect to Staphylococcus epidermidis biofilms compared to Staphylococcus aureus, Escherichia coli, and Candida albicans. Less biofilm residues made the regrowth of S. epidermidis also limited. The combination of uPA with antibiotic showed better antimicrobial and antibiofilm activity than uPA alone or heparin-based ABL in vitro and in vivo. Among HD patients, uPA-based ABL did not cause any obvious adverse affects, and it was more effective in treating coagulase-negative Staphylococci related CRBSI than other microorganisms.
Conclusions:
The combination of uPA and a therapeutic plasma concentration of sensitive antibiotic can work together to effectively remove coagulase-negative S. epidermidis embedded in biofilms in vitro. uPA-based ABL is safe and effective therapeutic intervention for HD patients with CRBSI, especially compared to heparin-based ABL.
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