Combination of Systemic and Lock-Therapies with Micafungin Eradicate Catheter-Based Biofilms and Infections Caused by
Ruta Petraitiene1, Vidmantas Petraitis1, Myo H Zaw1,2
1Transplantation-Oncology Infectious Diseases Program, Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine of Cornell University, 1300 York Ave., New York, NY 10065, USA.
Abstract:
Vascular catheter-related infections, primarily caused by Candida albicans and Candida parapsilosis, pose significant challenges due to the formation of biofilms on catheters, leading to refractory disease and considerable morbidity. We studied the efficacy of micafungin in systemic and lock therapies to eliminate catheter-based biofilms and deep tissue infections in experimental central venous catheter (CVC)-related candidemia in neutropenic rabbits. Silastic CVCs in rabbits were inoculated with 1 × 103 CFU/mL of C. albicans or C. parapsilosis, establishing catheter-based biofilm, and subjected to various treatments. Neutropenic rabbits treated with a combination of lock therapy and systemic micafungin demonstrated the most significant reduction in fungal burden, from 5.0 × 104 to 1.8 × 102 CFU/mL of C. albicans and from 5.9 × 104 to 2.7 × 102 CFU/mL of C. parapsilosis (p ≤ 0.001), in the CVC after 24 h, with full clearance of blood cultures after 72 h from treatment initiation. The combination of lock and systemic micafungin therapy achieved eradication of C. albicans from all studied tissues (0.0 ± 0.0 log CFU/g) vs. untreated controls (liver 7.5 ± 0.22, spleen 8.3 ± 0.25, kidney 8.6 ± 0.07, cerebrum 6.3 ± 0.31, vena cava 6.6 ± 0.29, and CVC wash 2.3 ± 0.68 log CFU/g) (p ≤ 0.001). Rabbits treated with a combination of lock and systemic micafungin therapy demonstrated a ≥2 log reduction in C. parapsilosis in all treated tissues (p ≤ 0.05) except kidney. Serum (1→3)-β-D-glucan levels demonstrated significant decreases in response to treatment. The study demonstrates that combining systemic and lock therapies with micafungin effectively eradicates catheter-based biofilms and infections caused by C. albicans or C. parapsilosis, particularly in persistently neutropenic conditions, offering promising implications for managing vascular catheter-related candidemia and providing clinical benefits in cases where catheter removal is not feasible.
Insights
Combination therapy with micafungin effectively eradicates catheter-related candidemia by eliminating fungal biofilms. This approach offers a promising solution for treating infections caused by Candida species, especially in neutropenic patients.
Area of Science:
- Mycology
- Infectious Diseases
- Pharmacology
Background:
- Vascular catheter-related infections, primarily from Candida species, are challenging due to biofilm formation.
- Catheter-based biofilms lead to persistent infections and significant patient morbidity.
- Neutropenic conditions exacerbate the severity of candidemia.
Purpose of the Study:
- To evaluate the efficacy of micafungin in treating catheter-based biofilms and deep tissue infections in experimental central venous catheter (CVC)-related candidemia.
- To assess the combined effect of systemic and lock micafungin therapies.
- To investigate treatment outcomes in neutropenic rabbits.
Main Methods:
- Experimental model of CVC-related candidemia in neutropenic rabbits using Candida albicans or Candida parapsilosis.
- Application of various treatment regimens, including systemic and lock micafungin therapies.
- Quantification of fungal burden in CVCs, blood, and tissues; monitoring of serum (1→3)-β-D-glucan levels.
Main Results:
- Combined systemic and lock micafungin therapy significantly reduced fungal burden in CVCs for both C. albicans and C. parapsilosis.
- This combination therapy achieved full clearance of blood cultures within 72 hours and eradicated C. albicans from all studied tissues.
- Significant reductions in C. parapsilosis in treated tissues (except kidney) and decreased serum (1→3)-β-D-glucan levels were observed.
Conclusions:
- Combining systemic and lock micafungin therapies is highly effective in eradicating catheter-based biofilms and candidemia.
- This treatment strategy shows significant promise for managing vascular catheter-related candidemia in neutropenic patients.
- The findings support the use of combination micafungin therapy when catheter removal is not feasible.
