Efficacy of higher doses of tobramycin and vancomycin released from commercial local delivery device

Abstract

Event Abstract Back to Event Efficacy of higher doses of tobramycin and vancomycin released from commercial local delivery device Carlos Wells1, Michael Harris1, Ravi Patel1, Daniel Ahn2, Warren Haggard1 and Jessica A. Jennings1 1 The University of Memphis, Biomedical Engineering, United States 2 Vanderbilt University, Biomedical Engineering, United States Introduction: Prevention strategies for biofilm infection are increasingly sought as treatment of existing biofilm infection is limited to removal of the implant. A commercial chitosan sponge under investigation for use as a wound dressing has also been shown to locally deliver antibiotics. For infection treatments, clinicians may select readily available concentrated intravenous (IV) drip antibiotic solutions which are up to 10X more concentrated than concentrations investigated in previous studies [1]. This study investigated whether loading with common IV drip concentrations of vancomycin and tobramycin combined could extend the duration of active antibiotic elution in sponges of various sizes and with different elution volumes representative of low and high volumes of vascularity/fluid flow in the wound. Methods: Chitosan sponges (Bionova Medical) sized 25 and 100 cm2 were loaded with a solution of 20 mg/ml vancomycin and 24 mg/ml tobramycin combined representative of reconstituted IV drip formulas. Samples (n=4 in each group) were then placed in 20, 50, 80, or 200 mL of phosphate buffered saline (PBS) and incubated under constant shaking. PBS was refreshed and antibiotic concentration was determined in eluates after 3, 24, 72, 168, 336, and 672 h by measuring eluate absorbance at λ = 280 (vancomycin) and λ = 450 (tobramycin derivative [2]). Activity of elutes was evaluated using turbidity and zone of inhibition (ZOI) testing. Results: The sponges delivered levels of vancomycin above the minimum inhibitory concentration (MIC) against S. aureus of 1 µg/mL throughout the 28 day study (Fig 1). Concentrations of tobramycin remained above the MIC of 20 µg/mL against P. aeruginosa for the first 7 days, with sub-MIC concentrations for the 100 cm2, 200 mL (large sponge, high elution volume) samples at 336 and 672 h, and the 25 cm2, 50 mL (small sponge, high elution volume) samples at 672 hours (Fig 2). Activity of eluted antibiotic in samples above MIC was confirmed by turbidity<0.1 and ZOIs>1 mm when tested against S. aureus and P. aeruginosa (Fig 3). Discussion: The chitosan sponges may have an increased potential to inhibit biofilm related infections when loaded with higher concentrations of antibiotic. Antibiotic concentration at each time point was directly related to the ratio of initial sponge size to the volume of fluid the sponge was subjected to. These elution profiles, while similar to curves for lower loading levels [1], were active against bacteria for a longer duration. This preliminary study provides an approach to predict loading ranges to maintain antibiotic efficacy while minimizing systemic concentrations of toxic antibiotics. Conclusion: Commercially available chitosan sponges can be used to deliver therapeutically effective doses of local antibiotics over a period of time determined by sponge size and initial antibiotic concentrations. Lauren Wilson; Marmadou Diallo; Jonathan Tapp; Parwinder Singh