Ciprofloxacin and Rifampin Dual Antibiotic-Loaded Biopolymer Chitosan Sponge for Bacterial Inhibition

Area of Science:

• Orthopedics
• Infectious Diseases
• Biomaterials Science

Background:

• Complex extremity wounds in Wounded Warriors are susceptible to microbial contamination, potentially leading to severe outcomes like amputation.
• Biofilm formation by microbes, including vancomycin-resistant Staphylococcus aureus, poses a significant challenge in treating these wounds and preventing hospital-acquired infections.
• Current treatment limitations necessitate novel strategies for effective local antibiotic delivery to combat polymicrobial infections and prevent biofilm development.

Purpose of the Study:

• To investigate the efficacy of locally delivered ciprofloxacin and rifampin for preventing biofilm formation in complex extremity wounds with implanted fixation devices.
• To evaluate the elution characteristics of ciprofloxacin and rifampin from a chitosan-based local delivery system.
• To assess the in vivo performance of this antibiotic combination in a preclinical model of orthopedic hardware-associated polymicrobial infection.

Main Methods:

• In vitro assays were conducted to determine the combined effect of ciprofloxacin and rifampin against Pseudomonas aeruginosa and their elution from chitosan sponges.
• A preclinical in vivo orthopedic hardware-associated polymicrobial model using Staphylococcus aureus and Escherichia coli was established.
• The efficacy of locally delivered ciprofloxacin and rifampin via chitosan sponges was evaluated for bacterial clearance and biofilm inhibition in the in vivo model.

Main Results:

• In vitro studies showed an additive effect of ciprofloxacin and rifampin against Pseudomonas aeruginosa, with both antibiotics actively eluting from the chitosan sponge.
• In the in vivo model, the combination of ciprofloxacin and rifampin delivered via chitosan sponges achieved complete clearance of Staphylococcus aureus and Escherichia coli.
• While Escherichia coli was detected in bone in untreated animals, it did not form biofilm on fixation wires, highlighting the challenge of hardware-associated infections.

Conclusions:

• Locally delivered ciprofloxacin and rifampin via antibiotic-loaded chitosan sponges demonstrate significant potential for inhibiting biofilm formation and treating complex extremity wound infections.
• This approach allows for tailored antibiotic selection and concentration for effective infection control, particularly in cases involving orthopedic hardware.
• The findings support the clinical utility of chitosan-based local delivery systems as a promising strategy to prevent and manage challenging microbial contaminations in Wounded Warrior extremity injuries.