Local Delivery of Amikacin and Vancomycin from Chitosan Sponges Prevent Polymicrobial Implant-Associated Biofilm

Abstract

Military personnel have high risk for infection, particularly those with combat-related extremity trauma. Administration of multiple or broad-spectrum antibiotics provides clinicians with a strategy for preventing biofilm-based medical device infections. Selection of effective antibiotic combinations based on common pathogens may be used to improve chitosan wound dressing sponge-based local antibiotic delivery systems. In vitro assays in this study demonstrate that vancomycin and amikacin have a synergistic relationship against a strain of osteomyelitis-producing Gram-positive Staphylococcus aureus, although an indifferent relationship was observed against Gram-negative Pseudomonas aeruginosa. In an in vivo model of orthopedic hardware-associated polymicrobial (S. aureus and Escherichia coli) biofilm, chitosan sponges loaded with a combination of vancomycin and amikacin at 5 mg/mL each showed a greater percentage of complete clearance, 50%, than either antibiotic alone, 8.33%. Doubling the loading concentration of the combination achieved a complete clearance rate of 100%, a four log-fold reduction of S. aureus on the wire and a six log-fold reduction in bone. E. coli was detected in bone of untreated animals but did not form biofilm on wires. Results demonstrate the clinical potential of chitosan sponges to prevent infection and illustrates antibiotic selection and loading concentrations necessary for effective biofilm prevention.

Therapeutics and delivery vehicles for local treatment of osteomyelitis

“…Sponges for local and rapid treatment of osteomyelitis appears to be a growing area of interest, particularly in military applications, as they are readily available to pack into traumatic wounds and rapidly deliver therapeutics directly to the site of infection. 29 Reported materials of sponges include chitosan, chitosan-polycaprolactone blends, and collagen, which have been used to deliver gentamicin, 116,152 ciprofloxacin, 29,153 amikacin, 154,155 vancomycin, [154][155][156] rifampin, 29 and others. 157 In two comparative studies in humans, gentamicin loaded collagen sponges matched the efficacy of traditionally used PMMA beads in osteomyelitis treatment, while reducing the need for secondary surgical procedures.…”

<p>The Osteogenic Effect of Local Delivery of Vancomycin and Tobramycin on Bone Marrow Stromal Cells</p>

“…First, only two antibiotics were included in our study. The osteogenesis of other antibiotics, such as gentamicin, 22 ampicillin, 23 and amikacin, 24 should be further explored. Second, we only use the clinical concentration of two antibiotics in the current study.…”

Biomaterial design strategies to address obstacles in craniomaxillofacial bone repair

“…116 However, loading these chitosan sponges with antibiotics can increase clearance of S. aureus more so than antibiotic application alone. 117 Honey in particular has been of recent focus due to its low pH and hydrogen peroxide content attributing to its antibacterial properties, and has been incorporated into hydrogels and on the surface of materials as honey-needles to kill bacteria. [118][119][120] Infection can occur during implantation of a biomaterial and remain unknown aer surgery until it is too late, and the removal of the infected biomaterial is necessary.…”