Development of a Novel Collagen Wound Model To Simulate the Activity and Distribution of Antimicrobials in Soft Tissue during Diabetic Foot Infection.
Diabetes has major implications for public health, with diabetic foot ulcers (DFUs) being responsible for significant morbidity and mortality. A key factor in the development of nonhealing ulcers is infection, which often leads to the development of biofilm, gangrene, and amputation. A novel approach to treating DFUs is the local release of antibiotics from calcium sulfate beads. We have developed a novel model system to study and compare the release and efficacy of antibiotics released locally, using collagen as a substrate for biofilm growth and incorporating serum to mimic the biochemical complexity of the wound environment. We found that our soft-tissue model supports the growth of a robust Pseudomonas aeruginosa biofilm, and that this was completely eradicated by the introduction of calcium sulfate beads loaded with tobramycin or gentamicin. The model also enabled us to measure the concentration of these antibiotics at different distances from the beads and in simulated wound fluid bathing the collagen matrix. We additionally found that a multidrug-resistant Staphylococcus aureus biofilm, nonsusceptible to antibiotics, nonetheless showed an almost 1-log drop in viable counts when exposed to calcium sulfate beads combined with antibiotics. Together, these data suggest that locally applied antibiotics combined with calcium sulfate provide surprising efficacy in diabetic foot infections and offer an effective alternative approach to infection management. Our study additionally establishes our new system as a biochemically and histologically relevant model that may be used to study the effectiveness of a range of therapies locally or systemically for infected DFUs.
Medical Device Biology Group, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom.
Bianca L
0000-0003-1843-618X
BL
Price
Antimicrobial Reference Laboratory, Microbiology Department, Bristol, United Kingdom.
Andrew M
AM
Lovering
University of Manchester, Manchester Diabetes Centre, Manchester, United Kingdom.
Frank L
FL
Bowling
Medical Device Biology Group, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom curtis.b.dobson@manchester.ac.uk.
Curtis B
CB
Dobson
D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects; D002133:Calcium Sulfate / Q000737:chemistry; D003094:Collagen / Q000378:metabolism; D017719:Diabetic Foot / Q000150:complications* / Q000378:metabolism; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D005839:Gentamicins / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000472:pathogenicity; D008826:Microbial Sensitivity Tests; D011552:Pseudomonas Infections / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000472:pathogenicity; D018461:Soft Tissue Infections / Q000188:drug therapy* / Q000209:etiology; D013203:Staphylococcal Infections / Q000188:drug therapy; D014031:Tobramycin / Q000493:pharmacokinetics / Q000494:pharmacology; D014640:Vancomycin / Q000494:pharmacology; D014946:Wound Infection / Q000188:drug therapy* / Q000209:etiology
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D014640:Vancomycin; D003094:Collagen; D014031:Tobramycin; D002133:Calcium Sulfate